ETAS_MCQ_03 b genodermatoses

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  • 1. 125) A patient with Bloom Syndrome is most likely to have which laboratory abnormalities:A. Elevated IgEB. Positive ANAC. ThrombocytopeniaD. Macrocytic anemiaE. Decreased immunoglobulinsCorrect ChoiceBloom syndrome is an autosomal recessive disorder due to a mutation in the BLM gene which codesfor a DNA helicase. Patients have impaired DNA repair after UV exposure and increasedphotosensitivity. Clinical features include photodistributed erythema, cheilitis, high-pitched voice,hypogonadism, and increased risk for leukemia, lymphoma and GI adenocarcinoma. Laboratoryevaluation reveals decreased IgA, IgM and IgG leading to increased risk of respiratory infections126) A patient with hypohydrosis and hyperpyrexia, anodontia, and sparse hair has whichsyndrome:A. Dyskeratosis congenitaB. Papillon LefevreC. Pachyonychia congenitaD. Hidrotic ectodermal dysplasiaE. Anhidrotic ectodermal dysplasiaCorrect ChoiceAnhidrotic ectodermal dysplasia is an x-linked recessive disorder which presents with the triad ofhypohydrosis (or anhidrosis) with hyperpyrexia, anodontia (other dental findings include peg teeth,molars with hooked cusps) and sparse hair. Patients tend to overheat127) A mentally retarded patient is found to also have a malar rash and downward lensdisplacement. Another clinical feature might include:A. periodontitisB. hypertrichosisC. deep venous thrombosesCorrect ChoiceD. multiple neviE. short statureThe above described patient has homocystinuria, an autosomal recessive disorder caused by adeficiency in cystathionine beta-synthase, leading to an accumulation of homocysteine. Clinicalfeatures include: malar flush, DVT’s, livedo reticularis, leg ulcers, downward lens displacement,myopia, glaucoma, sparse fine hair, mental retardation, and musculoskeletal anomalies128) Which type of epidermolysis bullosa is associated with mitten deformities of the hands?A. Generalized atrophic benign epidermolysis bullosa (GABEB)B. Dominant dystrophicC. Weber-CockayneD. Recessive dystrophic Correct ChoiceE. Herlitz type 47
  • 2. The recessive dystrophic type of epidermolysis bullosa is associated with chronic hand ulcersresulting in scarring that causes mitten deformities. These chronic scars often result in theformation of fatal squamous cell carcinomas.129) Nevoid basal carcinoma syndrome (Gorlin syndrome) is autosomal dominant transmittedmutation of the patched gene. Symptoms include innumberable basal cell carcinomas, painfulodontogenic jaw keratocysts, palmoplantar pits, frontal bossing, bifid ribs and what other bonyabnormality?A. OsteopoikilosisB. Polyostotic fibrous dysplasiaC. Calcification of falx cerebriCorrect ChoiceD. Sphenoid wing dysplasiaE. Stippled epiphysesCalcification of falx cerebri is seen in Gorlins syndrome. CHILD syndrome and chondrodysplasiapunctata both can exhibit stippled epiphyses. Polyostotic fibrous dysplasia is found in McCune-Albright syndrome, osteopoikilosis in seen in Buschke-Ollendorf syndrome. Sphenoid wing dysplasiais seen in neurofibromatosis type I130) A double row of eyelashes is associated with:A. Lymphedema-distichiasis syndromeCorrect ChoiceB. Hunters syndromeC. Cornelia de Lange syndromeD. Rubinstein-Taybi syndromeE. Russell-Silver syndromeA double row of eyelashes is defined as distichiasis and is associated with the Lymphedema-distichiasis syndrome. This syndrome is transmitted in an autosomal dominant fashion and isrelated to a mutation in FOXC2. Findings include late onset lymphedema, distichiasis, cornealirritation, ectropion, webbed neck and congenital heart defects. The remaining syndromes do notinclude distichiasis as a feature.131) Patients with Russell-Silver syndrome exhibit:A. Broad thumbsB. Clinodactyly of fifth fingerCorrect ChoiceC. Peg teethD. Shortened 4th and 5th metacarpalsE. Osteopathia striataCharacteristic features of Russell-Silver include short stature, bony asymmetry, triangular facies,clinodactyly of fifth finger, and precocious sexual development with cryptochordism/hypospadias.Broad thumbs are seen in Rubinstein-Taybi and shortened fourth and fifth metacarpals are seen inTurner syndrome. Osteopathia striata is characteristic of focal dermal hypoplasia132) A child presents with macroglossia, exopthalmos and gigantism. He has a history ofomphalocele repair and has circular depressions on the rim of the posterior helices. Although thissyndrome is most often transmitted in a sporadic manner, 15% of cases have defects in whichgene? 48
  • 3. A. FLT4B. VHLC. FOXC2D. ATME. KIP2Correct ChoiceKIP2 can be mutated in 15% of cases of Beckwith-Wiedemann Syndrome. KIP2 is a cyclin-dependent kinase inhibitor gene which acts as a negative regulator of cell proliferation. Thesechildren have an increase risk of Wilms tumor and organomegaly. In addition to the circular eardepression, they can also have a linear earlobe crease. The remaining genes are mutated in othersyndromes with vascular disorders as a component: ATM in ataxia telangectasia, VHL in Von Hippel-Lindau, FLT4 in Hereditary lymphedema and FOXC2 in Lymphedema-distichiasis syndrome133) Which of the following is defective in Ehlers-Danlos syndrome (EDS) with congenital adrenalhyperplasia?A. Lysyl hydroxylaseB. Tenascin-XCorrect ChoiceC. Lysyl oxidaseD. All of these answers are correctE. None of these answers are correctTenascin-X defects are associated with EDS and with congenital adrenal hyperplasia. The phenotypeis that of typical EDS with hyperextensible skin, hypermobile joints, and tissue fragility. Lysyloxidase is defective in X-linked EDS (type V) and Occipital horn syndrome (type IX). Lysylhydroxylase is defective in ocular-scoliotic (type VI) EDS134) What is the most likely gene mutation in this individual who has migratory patches and fixedplaques as depicted in this picture?A. Connexin 26B. Connexin 30.3 and 31Correct ChoiceC. Keratins 1 and 10D. Calcium ATPase 2C1E. LoricrinErythrokeratodermis variabilis is an autosomal dominant disease characterized by transient patchesof geographic erythema and fixed hyperkeratotic plaques. The disease is due to gene defects inconnexin 30.3 and 31135) The gene that is responsible for this disease also plays a pathogenic role in what otherdisorder?A. MastocytosisCorrect ChoiceB. SarcoidosisC. Hereditary AngioedemaD. Mycosis FungoidesE. Waardenburg Syndrome 49
  • 4. Piebaldism is an autosomal dominant disease characterized by depigmented patches and a whiteforelock. It is caused by a mutation in the c-kit proto-oncogene. Mutations in c-kit have also beenfound in the peripheral cells of individuals with mastocytosis136) Menkes kinky hair syndrome is associated most commonly with which of the following hairabnormalities?A. Pili triangulati et canaliculatiB. Pili tortiCorrect ChoiceC. None of these options are correctD. Trichorrhexis invaginataE. Trichorrhexis nodosaWhile pili torti is not exclusively found in Menkes kinky hair syndrome, this is the most common hairabnormality found. Trichorrhexis nodosa can be also seen. Trichorrhexis invaginata is commonlyfound in Netherton syndrome. Pili triangulati et canaliculati is the finding seen in Uncombable hairsyndrome.137) Medulloblastomas are seen in which of the following syndromes?A. Familial cylindromatosisB. Nevoid basal cell carcinomas syndrome Correct ChoiceC. Bazex syndromeD. Nicolau-Balus syndromeE. Birt-Hogg-Dube syndromeNevoid basal cell carcinomas syndrome (Gorlin syndrome) is an autosomal dominant conditioncaused by mutations in the patched gene, which is involved in the hedgehog signaling pathway.Patients develop innumerable BCCs, palmoplantar pits, painful odontogenic jaw keratocysts, frontalbossing, bifid ribs, and calcification of the falx cerebri. Medulloblastomas and ovarian fibromas andfibrosarcomas are associated with this condition138) Which of the following is caused by a defect in a gap junction protein?A. Hailey-haileyB. Epidermolysis bullosa simplexC. Bullous ichthyosis of siemensD. Erythrokeratoderma variabilisCorrect ChoiceE. Dyskeratosis congenitaErythrokeratoderma variabilis is also known as Mendes da Costa Syndrome. It is caused by a defectin connexin 31, a gap junction protein. EB simplex is caused by a mutation in keratins 5 & 14,Hailey-Hailey is caused by a mutation in calcium transporters, dyskeratosis congenita is caused by adefect in rRNA synthesis, and bullous icthyosis of Siemens is caused by mutations in keratin 2e139) Which of the following syndromes is associated with markedly increased IgE levels, coldabscesses and a characteristic coarse facies?A. Chronic granulomatous disease 50
  • 5. B. Wiskott-Aldrich syndromeC. Job syndromeCorrect ChoiceD. Leiners diseaseE. Severe combined immunodeficiencyJob syndrome or Hyper IgE syndrome is characterized by these findings. In addition, there is aperipheral eosinophilia, eczematous dermatitis, frequent bronchitis and pneumonia, otitis media andsinusitis. The other listed conditions are associated with immunodeficiency. Wiskott-Aldrich canhave eczematous dermatitis and all of these syndromes will have abnormal infections. They do nothave markedly increased levels of IgE like Job syndrome.140) Pruritus is Sjogren Larsson syndrome is attributed to accumulation of what molecule(s)?A. LeukotrieneCorrect ChoiceB. HistamineC. Bile saltsD. None of these answers are correctE. All of these answers are correctAccumulation of leukotriene B4 contributes to pruritus in Sjogren Larsson syndrome. Leukotrieneinhibitors may be helpful in controlling symptoms.141) Which of the following syndromes is associated with tricholemmomas?A. RasmussensB. Bannayan-Riley-RuvacalbaCorrect ChoiceC. BasexD. Birt-Hogg-DubeE. Brooke-SpieglerTricholemmomas are seen in Bannayan-Riley-Ruvacalba syndrome. This is an autosomal dominantcondition with macrocephaly, lipomas, hemangiomas, skeletal abnormalities, lymphangiomacircupscriptum, angiokeratomas, penile lentigines, acanthosis nigricans, and achrocrodons. There isan increased incidence of breast, thyroid, and GI cancers. Tricholemmomas are also seen in Cowdensyndrome142) Electron microscopic examination of a hair shaft reveals a canal-like groove along the shaft ofa triangular-shaped hair. This patient has:A. Menke’s Kinky Hair syndromeB. Spun-glass hairCorrect ChoiceC. TrichothiodystrophyD. Netherton’s syndromeE. Bjornstad syndromePili trianguli et canaliculi is also known as Spun-glass hair or Uncombable Hair Syndrome. Nethertonpatients have trichorexis invaginata, Menke’s kinky hair patients have short, brittle sparse hairs,“tiger tail” hair is seen in trichothiodystrophy, and pili torti is seen in bjornstad syndrome 51
  • 6. 143) A patient with coarse facies, broad nasal bridge, and extensive eczema might be expected tohave which abnormal laboratory value?A. HypertriglyceridemiaB. High Copper levelsC. High IgE levelsCorrect ChoiceD. Low Zinc levelsE. AnemiaPatients’ with Hyper IgE Syndrome (Job syndrome) have impaired regulation of the IgE function andincreased susceptibility to infections. In addition to recurrent cutaneous infections including coldabscesses, patients have widespread eczematous dermatitis, recurrent sinopulmonary infectionsand typically have coarse facies with broad nasal bridge and a prominent nose144) Reticulate pigmentation of skin, poikiloderma, alopecia, nail atrophy, premalignant oralleukoplakia, and a Fanconi-type pancytopenia resulting in early death in addition to posterior fossamalformations is characteristic of which of the following syndromesA. Cockayne syndromeB. Hoyeraal-Hreidarsson syndromeCorrect ChoiceC. Bloom syndromeD. Dyskeratosis congenitaE. Wiskott-Aldrich syndromeHoyeraal-Hreidarsson syndrome is has all of the features of dyskeratosis congenita plus posteriorfossa malformations. Bloom syndrome and Cockayne syndrome both have poikiloderma as features,but do not include posterior fossa malformations as part of the syndrome. Wiskott-Aldrich syndromedoes not include any of these findings145) Dyskeratosis congenita has all of the findings listed below EXCEPT:A. reticulate pigmentation of skin/poikilodermaB. alopeciaC. Mental retardationCorrect ChoiceD. Is allelic to Hoyerall-Hreidarsson syndromeE. Fanconi-type pancytopenia resulting in early deathMental retardation is not part of the spectrum of disease of dyskeratosis congenita. The remainingoptions are correct. Hoyerall-Hreidarsson syndrome has all of the findings of dyskeratosis congenitawith the addition of posterior fossa malformations146) In ataxia telangectasia, the ATM gene is mutated. The product of the ATM gene is an enzymewhich:A. participates in NF-kB activationB. binds transforming growth factor beta proteinC. responds to DNA damage by phosphorylating key DNA repair substratesCorrect ChoiceD. is the VEGF receptor 3 52
  • 7. E. is an inhibitor of G1 cyclin/Cdk complexesThe ATM gene is a member of the phosphatidylinositol-3 family of proteins that respond to DNAdamage by phosphorylating key substrates involved in DNA repair according to OMIM. Defects inendoglin (TGF beta3 binding protein) is deficient in Osler-Weber-Rendu syndrome. The VEGFreceptor 3 is defective in hereditary lymphedema. The NEMO gene is defective in IncontinentiaPigmenti. Its product, NF-kB essential modulator (NEMO) is a key activator in the NF-kB pathway.KIP2 is involved in AD Beckwith-Wiedemann syndrome and is an inhibitor of G1 cyclin/Cdkcomplexes147) Ichthyosis hystrix is characterized by the following gene defects?A. keratins 5 and 14B. keratins 1 and 10Correct ChoiceC. keratins 1 and 9D. none of these answers are correctE. keratins 6 and 16Ichthyosis hystrix or extensive epidermal nevi occurs secondary to a somatic mosaicism for keratins1 and 10. If the mosaicism occurs on gonadal cells, offspring may have full blown epidermolytichyperkeratosis (EHK).148) Mucosal malignancy is a complication of:A. Oral hairy leukoplakiaB. Chronic candidiasisC. Focal epithelial hyperplasiaD. White sponge nevusE. Dyskeratosis congenitalCorrect ChoiceDyskeratosis congenital, also called Zinsser-Engman-Cole syndrome, is an X-linked recessivegenodermatosis caused by a mutation in DKC1. DKC1 encodes for dyskerin, which helps to maintaintelomeres through the pseudouridylation of rRNA. Features of this condition include reticulate gray-brown hyperpigmentation, dystrophic nails, alopecia and Fanconi’s type pancytopenia. Patients mayhave premalignant leukoplakia which should be followed closely149) What condition is associated with this finding of inflammatory keratotic facial papules whichmay result in scarring and atrophy?A. Reiters syndromeB. ChloracneC. Keratosis pilarisD. Ulerythema ophryogenesCorrect ChoiceE. Systemic lupus erythematosusUlerythema ophryogenes is a rare disorder that affects children and young adults. It is characterizedby keratosis pilaris atrophicans and loss of lateral third of eyebrow150) Ichthyosis linearis circumflexa is one of the findings seen in the syndrome caused by which ofthe following genes? 53
  • 8. A. SLURP1B. CYLDC. GJB2D. LMX1BE. SPINK5Correct ChoiceThe SPINK5 gene encodes for LEKTI, a serine protease inhibitor important in the regulation ofproteolysis in epithelia formation and keratinocyte terminal differentiation, is mutated in Netherton’sSyndrome. Other findings include: trichorrhexis invaginata (bamboo, ball and socket hair), atopicdermatitis, and anaphylaxis from food allergy. SLURP1 is mutated in Mal de Maleda, GJB2 inVohwinkel’s syndrome, LMX1B in Nail-Patella syndrome, and CYLD in Familial Cylindromiasis151) What is the mode of transmission for lamellar ichthyosis?A. sporadicB. X-linked dominantC. autosomal dominantD. autosomal recessiveCorrect ChoiceE. X-linked recessiveLamellar ichthyosis which is characterized by collodian membrane in newborns and platelike scale inchildren and adults is an autosomal recessive syndrome. The gene defect is transglutaminase 1(TGM1152) Which of the following diseases is caused by a mutation in a gap junction protein?A. Schopf-Schulz-Passarge syndromeB. Vohwinkel syndrome (classic) Correct ChoiceC. Striated PPKD. Mal de MeledaE. Vohwinkel syndrome (ichthyotic)Classic Vohwinkel syndrome is caused by mutations in connexin 26, a gap junction protein.Ichthyotic Vohwinkel syndrome is caused by mutations in loricrin and has ichthyosis but notdeafness153) Which of the following are cutaneous features of Marfan syndrome?A. Dermatofibrosis lenticularis and striaeB. Fat herniation and cutaneous atrophyC. Striae and elastosis perforans serpiginosa Correct ChoiceD. Loose skin and crumpled earsE. Sclerodermoid changes and dyspigmentationMarfan syndrome is an autosomal dominant disorder caused by mutations in fibrillin 1 and 2.Patients have tall stature, arachnodactyly, pectus excavatum, high-arched palate, joint laxity,ectopia lentis with upward dislocation, dilated aorta with rupture, mitral valve prolapse, striae, andelastosis perforans serpiginosa 54
  • 9. 154) What gene defect would you expect to find in a child with white forelock, dystopia canthorum,and upper limb abnormalities?A. MITFB. Endothelin-3C. Pax3Correct ChoiceD. SOX10E. C-kit proto-oncogeneWaardenburgs syndrome is characterized by depigmented patches, white forelock, and deafness.Both type 1 and 3 are caused by mutations in Pax3. Type 3 is also associated with limbabnormalities. MITF and SOX10 defects are responsible for types 2 and 4 respectively. C-kit proto-oncogene mutatios are seen in piebaldism155) Palmoplantar keratoderma with deafness is caused by a defect in which gene?A. unknownB. PlakophilinC. lysosomal papain like cysteine proteinaseD. SLURP-1E. mitochondrial serine transferase RNACorrect ChoicePalmoplantar keratoderma with deafness is caused by a defect in mitochondrial serine transferaseRNA. A defect in SLURP-1 causes Mal de Meleda. A defect in plakophilin causes ectodermal dysplasiawith skin fragility. A defect in cathepsin C lysososomal papain like cysteine proteinase causesPapillon LeFevre and Haim Munk.156) A Puerto Rican woman is seen in clinic for a pruritic rash on her trunk. A punch biopsy isperformed. The biopsy site continues to bleed, with hematoma formation. The bleeding is eventuallycontrolled. On further exam, her skin and hair are light brown. She has a history of granulomatouscolitis. What it the most likely reason she had excess bleeding with a simple procedure?A. Her platelets lack dense bodies, causing excess bleeding Correct ChoiceB. Her Factor VIII levels are lowC. Her intrinsic factor is deficientD. She is congentially deficient in plateletsE. None of the answers are correctPlatelets without dense bodies cause excess bleeding in Hermansky-Pudlak syndrome. Otherfeatures of this condition include oculocutaneous albinism, ceroid lysosomal storage diseaseresulting in pulmonary fibrosis, granulomatous colitis157) Which of the following syndromes are linked to a PTEN gene mutation?A. CowdenB. All of these options are correctCorrect ChoiceC. Lhermitte-Duclos diseaseD. Banayan-Zonana 55
  • 10. E. ProteusPTEN gene produces a phosphatase the regulates the cell-cycle and apoptosis, therefore acting as atumor suppressor gene. Tissues affected by this mutation are those with increased proliferationsuch as epidermis, the oral and gastrointestinal mucosa, and the thyroid and breast epithelium. Allof the syndromes listed have mutations in PTEN.158) The combination of painful palmoplantar keratoderma and pseudoherpetic keratitis ischaracteristic of which of the following syndromes?A. Naxos syndromeB. Howel-Evans syndromeC. Richner-Hanhart syndrome Correct ChoiceD. Schopf-Schulz-Passarge syndromeE. Vohwinkel syndromeRichner-Hanhart syndrome (tyrosenemia type II) is an autosomal recessive disorder caused by adeficiency in hepatic tyrosine aminotransferase. This disease is characterized by painful PPK,pseudoherpetic keratitis and blindness. Treatment is low-tyrosine/phenylalanine diet159) Epidermal nevus syndromes inheritance pattern is:A. Autosomal dominantB. X-linked dominantC. X-linked recessiveD. Autosomal recessiveE. sporadicCorrect ChoiceEpidermal nevus syndrome has many findings, including: sporadic inheritance, nevus unius lateris,capillary malformations, café au lait macules, mantal retardation and seizures, deafness,hemiparesis, hemihypertrophy of limbs, kyphoscoliosis and rare solid tumors. A biopsy is helpful torule out epidermolytic hyperkeratosis. If positive, the patient’s offspring are at risk for generalizedepidermolytic hyperkeratosis160) Ichthyosis bullosa of Siemens is a condition characterized by fragile blisters at birth,hyperkeratotic plaques on elbows/knees later in life, and a gene mutation in:A. Keratin 1/10B. Keratin 6a/16C. None of these options are correctD. Keratin 5/14E. Keratin 2eCorrect ChoiceKeratin 2e is mutated in ichythosis bullosa of Siemens. Keratin 5 and 14 are defective inepidermolysis bullosa simplex, 6a/16 in Pachyonychia congenital type I (Jadassohn-Lewandowsky),1/10 in epidermolytic hyperkeratosis and Unna-Thost PPK161) Spastic ditetraplegia is associated with which of the following disorders?A. Sjogren-Larsson syndrome Correct Choice 56
  • 11. B. X-linked ichthyosisC. Lamellar ichthyosisD. Refsum syndromeE. KID syndromeSjogren-Larsson syndrome is an autosomal recessive disorder caused by mutations in the fattyaldehyde oxidoreductase/alcohol dehydrogenase gene. This disorder is characterized by ichthyosis,spastic ditetraplegia, mental retardation, epilepsy, glistening dot retinal pigmentation, and dentalenamel dysplasia162) A sporadic syndrome affecting transcriptional coactivator CREB-binding protein is:A. Nonne-Milroy diseaseB. Rubinstein-Taybi syndromeCorrect ChoiceC. Cornelia de Lange syndromeD. Maffucci syndromeE. Blue rubber bleb nevus syndromeRubinstein-Taybi syndrome is caused by a sporadically transmitted defect in transcriptionalcoactivator CREB-binding protein. This gene is responsible for encoding a nuclear protein which actsas a co-activator of cAMP regulated gene expression. Findings of this syndrome include: capillarymalformation, short stature, broad thumbs, craniofacial abnormalities including beaked nose,mental retardation, strabismus, congenital heart defects and cryptorchidism. The other listedconditions are not related to this defect163) The arylsulfatase C gene is mutated in which disease?A. Naxos syndromeB. X-linked ichthyosisCorrect ChoiceC. Griscelli syndromeD. Haim-Munk syndromeE. Refsum syndromeArylsulfatase C is also known as steroid sulfatase and is mutated in X-linked ichthyosis. Thiscondition is inherited in a X-linked recessive pattern. Clinical findings include: brown scale sparingpalms, soles and flexures, comma-shaped corneal opacities, failure of labor progression andcryptorchidism. It is also mutated in X-linked recessive type chondrodysplasia punctata164) In one variant of epidermolysis bullosa simplex, those affected have muscular dystrophy inaddition to the skin findings. Which protein mutation has been linked to this finding?A. plectinCorrect ChoiceB. plakophilinC. plakoglobinD. desmocollinE. desmogleinA plectin mutation is linked with this subtype of epidermolysis bullosa simplex.165) A 3 year old boy presents with the findings seen in the image. He also has thrombocytopeniawith purpura and a history of recurrent pyogenic bacterial infections. What is the most likelydiagnosis in this child?A. Hyper-IgE syndrome 57
  • 12. B. Severe combined immunodeficiencyC. Wiskott-Aldrich syndromeCorrect ChoiceD. Leiner syndromeE. Chronic Granulomatous diseaseThe findings described are consistent with Wiskott-Aldrich syndrome. The characteristic triad can besimplified to the 3 Ps - Pruritus (atopic dermatitis), Purpura (thrombocytopenia leading to purpuraand other bleeding) and pyogenic infections. The remaining options are related to Wiskott-Aldrich inthat they all have immunodeficiency as a feature, but not the same spectrum of disease166) Pseudoxanthoma elasticum is caused by mutations in which of the following genes?A. Fibrillin 1B. Collagen 5C. ABCC6 gene Correct ChoiceD. Lysyl oxidaseE. Elastin genePseudoxanthoma elasticum is caused by mutations in the ABCC6 gene, which is an ATP-using celltransporter. Elastin and lysyl oxidase mutations cause cutis laxa, fibrillin 1 mutations cause Marfansyndrome, and collagen 5 mutations cause Ehlers-Danlos syndrome167) A 4 year old boy presents with 2 soft, dark-blue, compressible nodules on her extremities. Hismother has noted that these lesions have increased sweating and that they were present at birth.No one else in the family has had similar skin lesions. What step is indicated first to help determinethe diagnosis?A. Immediate referral to a gastroenterologistB. Biopsy of a skin lesionC. MRI of the abdomenD. Stool guiacCorrect ChoiceE. CBCBlue rubber bleb nevus syndrome is described above. There are multiple venous malformations onthe extremities and trunk, often present at birth to early childhood. The number of these lesionsincrease with age. The lesions may have increased sweating and can be combined with lymphatic-venous malformations. Skin lesions can be a clue to gastrointestinal venous malformations whichcan lead to secondary bleeding and anemia. The most reasonable screening test to determine if thepatient has GI hemorrhage is a stool guiac. An MRI or complete blood count can be helpful, but arenot the best test to start with. A skin biopsy is not indicated. If there is GI blood loss, evaluation bya gastroenterologist is useful168) A patient presents with starfish keratoses, pseudoainhum, honeycombed PPK, and generalizedichthyosis. What is the most likely genetic defect?A. Connexin 31B. Connexin 26 58
  • 13. C. LoricrinCorrect ChoiceD. Connexin 30E. Connexin 33The patient has Vohwinkel syndrome. This is an autosomal dominant syndrome with 2 clinicalvariants. The variant described above with generalized ichthyosis is due to a loricrin mutation. Inthe classic form with nonprogressive hearing loss connexin 26 is mutated169) The best screening test for hemochromatosis is:A. Complete Blood CountB. FerritinCorrect ChoiceC. HematocritD. Copper levelsE. TransferrinThe ferritin is the best screening test for hemochromatosis, an autosomal disease of increasedintestinal iron absorption. The other tests are not the best method for screening170) A 32 year old woman is 5 weeks pregnant and is diagnosed with hyperthyroidism. Her doctorgives her a prescription for on methimazole 10 mg PO tid. Which of the following fetal abnormalitiescould be caused by this exposure?A. Dermoid cystB. Aplasia cutis congenitaCorrect ChoiceC. Spina bifidaD. EncephaloceleE. MeningoceleIn-utero methimazole exposures has been linked to aplasia cutis congenita and should not be usedin pregnant women. The FDA pregnancy class is D. The other listed options are not linked withmaternal methimazole usage171) Ichthyosiform erythroderma in lines of Blaschko, follicular atrophoderma, and stippledepiphyses are characteristic of which of the following disorders?A. Refsum syndromeB. Netherton syndromeC. Erythrokeratodermia variabilisD. Sjogren-Larsson syndromeE. Chondrodysplasia punctata Correct ChoiceChondrodysplasia punctata is a peroxisomal disorder caused by mutations in several genes that isassociated with ichthyosiform erythroderma in lines of Blaschko, follicular atrophoderma, andstippled epiphyses 59
  • 14. 172) Yellow-brown depositions in Descemets membrane of the corneas is diagnostic for:A. NeurofibromatosisB. HemochromatosisC. Hepatolenticular degenerationCorrect ChoiceD. Pseudoxanthoma elasticumE. Diabetes mellitusHepatolenticular degeneration or Wilson Disease is caused by a defect in biliary excretion of copperleading to accumulation in the liver, brain, cornea, pretibial hyperpigmentation, hepatomegaly andcirrhosis. The Kayser-Fleischer ring is the yellow-brown copper deposition in Descemets membraneof the cornea. Other findings include ataxia, dysarthria and dementia. Hemochromatosis does nothave an eye finding. Neurofibromatosis has Lisch nodules and Pseudoxanthoma elasticum hasangioid streaks of the retina173) The gene defect in Griscelli Syndrome is:A. None of these answers are correctB. Myosin Va or Rab27aCorrect ChoiceC. LYST or CHS1D. P geneE. TRP1Myosin Va or Rab27a are defective in Griscelli syndrome, an AR syndrome with mild albinism,pancytopenia, immunodeficiency, neurologic symptoms and an accelerated phase similar toChediak-Higashi syndrome. LYST/CHS1 is defective in Chediak-Higashi syndrome. The P-gene ismutated in oculocutaneous albinism type 2 and TRP in oculocutaneous albinism type 3174) Mutation in lamin A (nuclear envelope protein) has been found in:A. Peutz-Jeghers syndromeB. Albright’s syndromeC. Marfan syndromeD. Buschek-Ollendorf syndromeE. Progeria (Hutchinson-Gilford) Correct ChoiceProgeria (Hutchinson-Gilford syndrome) is a sporadic condition characterized by lipoatrophy,sclerodermoid skin, alopecia, nail atrophy, craniomegaly with small face, muscle/bone wasting, andsevere premature atherosclerosis resulting in early death. Recent studies have shown thatmutations in nuclear envelope protein lamin A is associated with progeria175) The characteristic dental findings in patients with tuberous sclerosis are:A. Odontogenic cystsB. Retention of primary teethC. Peg teeth 60
  • 15. D. AnodontiaE. Enamel pitsCorrect ChoiceEnamel pits are the characteristic dental findings in tuberous sclerosis. Peg teeth are found inincontinentia pigmenti and anhidrotic ectodermal dysplasia. Anodontia is found in hypomelanosis ofito and incontinentia pigmenti. Odontogenic cysts are seen in Gorlin syndrome, and retention ofprimary teeth is characteristic of Job syndrome176) Urticaria pigmentosa is linked to a defect in the c-kit protooncogene. What autosomaldominant skin disease also has been linked to this defect?A. PiebaldismCorrect ChoiceB. Hypomelanosis of ItoC. Incontinentia pigmentiD. Waardenburg syndromeE. Hermansky-Pudlak syndromePiebaldism is linked to a defect in the c-kit protooncogene. Hypomelanosis of Ito has whorledhypopigmentation, occasional CNS defects, scoliosis and anodontia, a sporadic mutation.Waardenburg syndrome has 4 types, 1-3 are AD, 4 is AR. Type 1 & 3 have defects in PAX-3, 2 inMITF, and 4 in Sox10, endothelin-3 ligand or receptor genes. Hermansky-Pudlak syndrome is ARand most commonly linked to defects in HPS, a lysosomal transport protein and AP3B1, a proteinimportant in endocytic/exocytic sorting. Incontinentia pigmenti is an X-linked dominant syndromewith a defect in the NEMO gene177) Which of the following pairs of diseases are caused by mutations in DNA helicases?A. Xeroderma pigmentosum and Cockayne syndromeB. Muir-Torre syndrome and Birt-Hogg-Dube syndromeC. Cowden syndrome and Bannayan-Riley-Ruvalcaba syndromeD. Dyskeratosis congenita and Peutz-Jeghers syndromeE. Bloom syndrome and Rothmund-Thompson syndrome Correct ChoiceBloom Syndrome and Rothmund-Thompson syndromes are caused by autosomal recessivemutations in DNA helicases. The common features include photodistributed poikiloderma. Patientswith Bloom syndrome also demonstrate facial dysmorphism, hypogammaglobulinemia withrecurrent respiratory and gastrointestinal tract infections, hypogonadism, leukemias andlymphomas, gastrointestinal adenocarcinomas, and oral/esophageal SCCs. Patients with Rothmund-Thompson syndrome develop premalignant acral keratoses, alopecia, nail dystrophy, cataracts,hypogonadism, and occasional solid tumors178) Premature aging seen in Cockayne’s syndrome is caused by a mutation in which gene?A. ATM geneB. DNA helicase gene Correct ChoiceC. NEMO geneD. Patched gene 61
  • 16. E. TransglutaminaseCockayne’s syndrome is caused by a mutation in a DNA helicase gene, CSA or ERCC8. The conditionis defined by growth deficiency, premature aging, and pigmentary retinal degeneration. 75% ofpatient have photosensitive eruptions and severe cataracts before the age of 3 are associated withpoor prognosi179) Which of the following metals is deficient in the serum of patients with Menkes kinky hairsyndrome?A. BiotinB. SeleniumC. ZincD. IronE. CopperCorrect ChoiceMenkes kinky hair syndrome is transmitted in an X-linked recessive manner and is caused by amutation in ATP7A, an ATP-dependent copper tranporter. This defect results in low serum levels ofcopper. These individuals will have hair abnormalities such as sparse, hypopigmented brittle hair,eyelashes and eyebrows, lax skin, a "cupids bow" upper lip, CNS progressive deterioration,seizures, skeletal abnormalities and tortuous arteries. The other listed items are not associated withMenkes syndrome180) Which of the following is NOT a complication of Kasabach-Merritt Syndrome:A. ThrombocytopeniaB. Disseminated intravascular coagulationC. Gastrointestinal bleedingD. CHFE. AtaxiaCorrect ChoiceKasabach-Merritt Syndrome results from platelet trapping due to the presence of a single ormultiple large hemangiomas. Hematologic complications include thrombocytopenia,microangiopathic hemolytic anemia, DIC, and acute hemorrhage. The presence of largehemangiomas leads to high output failure (CHF) and can also compress on surrounding structures181) Patients with progeria typically die of which of the following conditions?A. Atherosclerotic heart disease Correct ChoiceB. Metastatic carcinomaC. Progressive systemic sclerosisD. InfectionE. Nail atrophyProgeria (Hutchinson-Gilford syndrome) is a sporadic condition characterized by lipoatrophy,sclerodermoid skin, alopecia, nail atrophy, craniomegaly with small face, muscle/bone wasting, andsevere premature atherosclerosis resulting in early death 62
  • 17. 182) On cutaneous exam, angiokeratoma corporis diffusum is characteristic of which of thefollowing conditions?A. Fabry diseaseB. SialodosisC. FucosidosisD. All of these options are correctCorrect ChoiceE. None of these options are correctFindings of angiokeratoma corporis diffusum are found in all three listed conditions. They cannot bydistinguished by skin exam183) The histologic image shown in this picture is associated with which of the followingsyndromes?A. Dyskeratosis congenitaB. Gorlin syndromeC. Banayan-Riley-Ruvalcaba syndromeD. Chediak-Higashi syndromeE. Multiple hamartoma syndromeCorrect ChoiceThe histologic picture shown is that of a sclerotic fibroma with the characteristic storiform/whorledpattern of collagen. The lesion has low cellularity with spindle cells. Banayan-Riley-Ruvalcabasyndrome shares the same gene defect as Multiple hamartoma syndrome (Cowden syndrome) but isnot associated with sclerotic fibromas. Dyskeratosis congenita is not associated with scleroticfibromas184) A patient with Crowe’s sign and an optic glioma has which of the following disorders?A. Tuberous sclerosisB. Neurofibromatosis IIC. Watson syndromeD. Lester iris syndromeE. Neurofibromatosis I Correct ChoiceThe diagnostic criteria for neurofibromatosis I include meeting 2 or more of the following 7 criteria:(1) >5 café au lait macules (CALMs) that are >5mm in a prepubertal person or >15 mm in apostpubertal person, (2) >1 neurofibroma or 1 plexiform neurofibroma, (3) axillary/inguinalfreckling (Crowe’s sign), (4) optic glioma, (5) >1 Lisch nodule (iris hamartoma), (6) sphenoiddysplasia, (7) 1st degree relative with neurofibromatosis I185) The most common cutaneous neoplasm associated with Muir Torre Syndrome is:A. Basal cell carcinoma with sebaceous differentiationB. Sebaceous adenomaCorrect Choice 63
  • 18. C. KeratoacanthomaD. Sebaceous carcinomaE. Squamous cell carcinomasMuir-Torre syndrome is an autosomal dominant disorder due to a DNA mismatch repair gene(MSH2). Patients present with sebaceous tumors, with adenomas being the most common(sebaceous carcinomas next common) and associated visceral malignancies such as colon cancer(most common).186) The finding of maltese crosses in the urine is characteristic of which of the followingconditions?A. Fabry diseaseCorrect ChoiceB. AlkaptonuriaC. Neimann-Pick diseaseD. Hunter syndromeE. Gaucher diseaseThe maltese cross finding in urine is characteristic of Fabry disease. Alkaptonuria will show darkurine with a pH > 7.0. There are no urinary findings in Hunter syndrome, Gaucher or Neimann-Pickdisease187) The gene PTEN (phosphatase and tensin homolog deleted on chromosome ten) is implicated inwhich of the following syndromes?A. CowdenB. None of the options are correctC. Banayan-Riley-RuvalcabaD. All of the options are correctCorrect ChoiceE. ProteusMutations in the PTEN gene are implicated in all three syndromes listed. There are conflictingreports in the literature regarding the linkage of Proteus and PTEN mutations. For further details,see OMIM #176920188) Which cutaneous finding is seen in patients with phenylketonuria?A. Pigment dilution of hair and skinCorrect ChoiceB. IchthyosisC. PhyrnodermaD. Angular stomatitisE. Erosive diaper dermatitisPhenylketonuria is an autosomal recessive condition caused by a mutation in the gene coding forphenylalanine hydroxylase. Defect in this enzyme results in accumulation of phenylalanine and itsmetabolites. Increased phenylalanine has toxic effects on the central nervous system in addition tocompetitively inhibiting tyrosine in melanogenesis. Inhibition of melanogenesis results in pigmentary 64
  • 19. dilution of the hair and skin. Other features of this condition include a predisposition to eczema,sclerodermoid changes of the skin, urine that has a distinctive "mousy" odor, psychomotor delay,mental retardation, seizures and hyperreflexia. A low-phenylalanine diet instituted early on canprevent these manifestations of the disease. The morbidity of phenylketonuria has improved sincethe advent of routine neonatal screening for this condition189) All of the following disorders are exacerbated by UV radiation except:A. Rothmund-Thomopson syndromeB. Hartnup’s diseaseC. Bloom syndromeD. Cockayne syndromeE. Refsum syndromeCorrect ChoiceRefsum’s syndrome is an autosomal recessive disorder caused by mutations in phytanoyl-CoAhydroxylase. Clinically, patients have mild icthyosis, cerebellar ataxia, polyneuropathy, salt andpepper retinitis pigmentosa, sensorineural deafness, and arrhythmias with heart block. They are notoverly sensitive to UV radiation190) Angioid streaks on retinal exam are characteristic of which of the following syndromes?A. Pseudoxanthoma elasticumCorrect ChoiceB. Choroid malformationsC. Salt & pepper retinitis pigmentosaD. Eyelid papillomasE. Lester irisAngioid streaks are characteristic of pseudoxanthoma elasticum. They are caused by rupture ofBruchs membrane of the choroid. Choroid malformations are found in Sturge-Weber syndrome,eyelid papillomas in xeroderma pigmentosum, Lester iris in Nail-patella syndrome and salt & pepperretinitis pigmentosa in Refsum syndrome191) Which one of the following is the most common oncogenic virus in patients withepidermodysplasia verruciformis?A. HPV-16B. HPV-5 Correct ChoiceC. HPV-13D. HPV-8E. HPV-33Epidermodysplasia verruciformis is a rare autosomal recessive disorder in which an impaired cellularimmunity allows widespread infection with certain subtypes of the human papilloma virus (HPV).Some of these lesions have a tendency for malignant transformation, most commonly those verrucacaused by HPV type 5 65
  • 20. 192) Crumpled ears are associated with which disorder?A. Marfan syndromeB. Buschke-Ollendorf syndromeC. Cutis laxaD. Ehlers-Danlos SyndromeE. Congenital contractural arachnodactyly Correct ChoiceCongenital contractural arachnodactyly is an autosomal dominant disorder caused by mutations infibrillin 2. Affected patients have long limbs, arachnodactyly, scoliosis, and crumpled ears193) Which of the following conditions is inherited in an X-linked dominant (XD) manner?A. Focal dermal hypoplasiaB. Chodrodysplasia punctataC. None of the answers are correctD. All of the answers are correctCorrect ChoiceE. CHILD SyndromeAll of the syndromes listed are XD. Other XD syndromes are: Incontinentia pigmenti and Bazexsyndrome194) What is the characteristic radiographic finding in type I Gaucher disease?A. OsteopoikilosisB. MelorheostosisC. EnchondromasD. Ehrlenmeyer flask deformityCorrect ChoiceE. Supernumerary vertebrae with extra ribsThe Ehrlenmeyer flask deformity is found in the femoral midshaft as well as aseptic necrosis of thefemoral head and widening of the distal femur. Endochondromas are seen in Maffucci syndrome,Osteopoikilosis in Buschke-Ollendorf syndrome, Melorheostosis (linear hyperostosis under affectedskin) in linear scleroderma and supernumerary vertebrae with extra ribs in incontinentia pigmenti195) A child presents with pretibial hyperpigmentation, ataxia, decreased motor coordination,cirrhosis, and decreased motor coordination. The physical exam which would reveal the mostspecific finding for this disease is:A. Slit-lamp eye examCorrect ChoiceB. Renal ultrasoundC. Hearing testD. ColonoscopyE. EKG 66
  • 21. Wilson’s disease (also known as hepatolenticular degeneration) is an autosomal recessive disorderresult in defective biliary excretion of copper, leading to copper accumulation in the liver, brain andcornea. Clinical features include hepatomegaly, cirrhosis, ataxia, dysarthria, decreased motorcoordination, pretibial hyperpigmentation, blue lunulae, and copper deposition in the cornea—Kayser-Fleisher ring, which can be diagnosed using a slit-lamp196) Eyelid string of pearls are seen in which of the following conditions?A. Hutchinson-Gilford syndromeB. Lipoid proteinosis Correct ChoiceC. Focal dermal hypoplasiaD. Gaucher’s diseaseE. Beare-Stevenson cutis gyrata syndromeLipoid proteinosis is an autosomal recessive condition characterized by yellow papules on the faceand oropharynx, eyelid string of pearls, hoarse voice, verrucous nodules of elbows and knees, andbean-shaped temporal and hippocampal calcification with occasional seizures. Histologically, thereare PAS+ deposits in the affected tissue197) What finding is seen on brain imaging of patients with Papillon-Lefevre Syndrome?A. calcification of the falx cerebriB. calcification of the hippocampusC. tram track calcificationsD. calcification of the duraCorrect ChoiceE. agenesis of the corpus callosumPappilon Lefevre Syndrome is an autosomal recessive syndrome characterized by transgredient PPKand periodontitis. There is a defect in cathepsin C. One sees dural calcification at the tentorium andchoroid attachments. Tram track calcifications are seen in STurge-WEber. CAlcification of the falxcerebri and agenesis of the corpus callosum is seen in basal cell nevus syndrome. Hippocampalcalcification is seen in lipoid proteinosi198) A patient with Klinefelter Syndrome may be expected to experience which of the following:A. Recurrent leg ulcersCorrect ChoiceB. Scarring alopeciaC. Recurrent pulmonary infectionsD. Gastroesophageal refluxE. Pulmonary valve stenosisKlinefelter syndrome results from nondisjunction during meiosis, leading to the XXY genotype.Patients are characteristically tall (long lower extremities) with scant body and pubic hair. Klinefelterpatients have numerous varicosities predisposing them to recurrent leg ulcers199) Which of the following is the first symptom of ataxia telangiectasias? 67
  • 22. A. Facial telangiectasesB. Conjunctival telangictasesC. Breast cancerD. Hematologic malgignancyE. Cerebellar ataxia Correct ChoiceAtaxia Telangiectasia (Louis-Bar syndrome) is an autosomal recessive disorder usually caused bymutations in the ATM gene, which is a chromosomal strand break repair enzyme. Cerebellar ataxiais the first sign, followed by telangiectases of the conjunctiva and skin. Thymic hypoplasiapredisposes to increased infections. There is increased sensitivity to ionizing radiation resulting inhematologic and solid tumors. Female carriers have increased risk of breast cancer200) Which type of epidermolysis bullosa simplex is associated with early death?A. Weber-CockayneB. Dowling-Maera Correct ChoiceC. Non-Herlitz variantD. Ogna variantE. Generalized (Koebner)The Dowling-Maera variant of epidermolysis bullosa simplex is associated with widespread bullae,significant mucous membrane and laryngeal/esophageal involvement, nail dystrophy, and earlydeath201) Patients with Darier’s disease are at increased risk for:A. MelanomaB. Basal cell carcinomaC. Lipid abnormalitiesD. Kaposi’s varicelliform eruptionCorrect ChoiceE. Decreased life spanKaposi’s varicelliform eruption is the condition in which viral infection occurs in a patient with a pre-existing chronic dermatitis. Darier’s disease is an autosomal dominant genodermatosis caused by amutation in ATP2A2 which encodes SERCA2. Cutaneous manifestations of warty, hyperkeratoticpapules in a seborrheic dermatitis, which may be infected with HSV or bacteria202) A patient with port wine stain on a lower extremity, hemihypertrophy of the limb andlymphatic and deep venouse insufficiency of the affected limb would be considered to have Klippel-Trenaunay-Weber syndrome. What additional feature would need to be present to define the patientas having Parkes-Weber syndrome?A. MacroglossiaB. Multiple cafe-au-lait maculesC. Arteriovenous fistulasCorrect Choice 68
  • 23. D. Cutis marmorataE. DistichiasisParkes-Weber syndrome has the additional feature of arteriovenous fistulas. The remaining featuresare not part of these syndromes203) What is the first sign seen in children with ataxia telangectasia syndrome?A. nystagmusB. cutaneous and bulbar conjunctival telangectasias Correct ChoiceC. recurrent viral or bacterial infectionsD. oculomotor apraxiaE. cerebellar ataxiaTelangectasias are the first sign of ataxia telangectasia syndrome (Louis-Bar). Other findings otherthan those listed above include: increased risk of lymphoma or breast carcinoma in heterozygotes,granulomas, cafe au lait macules. IgA, IgG2 and IgE will be decreased or absent. There is anincreased sensitivity to ionizing radiation204) A patient with this autosomal recessive disorder caused by a defect in helicase is an increasedrisk for which malignancy?A. Medullary thyroid carcinomaB. Renal cell carcinomaC. Acute leukemiaCorrect ChoiceD. Squamous cell carcinoma of the lungE. Prostate carcinomaBlooms syndrome is an autosomal recessive disorder caused by a mutation in DNA helicase. It ischaracterized by photodistributed erythema in a butterfly distribution, malar hypoplasia with aprominent nose, high pitched voice, and an increased risk for malignancy (acute leukemia,lymphoma, and GI adenocarcinoma205) In biopsies from blisters in patients with junctional epidermolysis bullosa, the split is found inthe:A. Basal cell layer of the epidermisB. Lamina densaC. Lamina lucidaCorrect ChoiceD. Squamous cell layer of the epidermisE. None of the answers are correctThe split seen in junctional epidermolysis bullosa is in the lamina lucida. The other locations can beinvolved in blistering disease, but not junctional epidermolysis bullosa 69
  • 24. 206) The NEMO gene is defective in Bloch-Sulzberger syndrome. What other syndrome has beenlinked with defects in the NEMO gene?A. Hypomelanosis of ItoB. Tuberous sclerosisC. PiebaldismD. Waardenburg syndromeE. Hypohidrotic ectodermal dysplasia with immune deficiency Correct ChoiceHypohidrotic ectodermal dysplasia with immune deficiency, is caused by mutations in the NEMO(IKK-gamma gene). As opposed to the X-linked dominant inheritance of Bloch-Sulzberger syndrome(incontinentia pigmenti), this is a X-linked recessive disorder. Hypomelanosis of Ito is sporadicallyinherited and is not linked with a gene defect. Tuberous sclerosis is autosomal dominant and hasbeen linked to defects in tuberin and hamartin tumor suppressor genes. Waardenburg syndromehas four subtypes, linked with the PAX-3, MITF and SOX10/endothelin-3 receptor genes. Piebaldismis linked to defects in the c-kit protooncogene207) What is the gene defect in harlequin fetus?A. transglutaminaseB. none of these answers are correctC. ABCC6D. steroid sulfatseE. ABCA12Correct ChoiceHarlequin fetus is an autosomal recessive disorder. The gene defect is ABCA12208) Regarding the inheritance of Ehlers-Danlos syndrome, which subtype is inherited in an X-linked recessive manner?A. The type with the lysyl oxidase deficiency Correct ChoiceB. The type with a collagen 5 defectC. The type with the lysyl hydroxylase deficiencyD. The type with a defect in procollagen aminopeptidaseE. The type with a collagen 3 defectLysyl oxidase deficiency is related to type V or X-linked Ehlers-Danlos syndrome (EDS). Type IX,also has x-linked recessive inheritance with mild symptoms of EDS with occipital exostoses andhernias. Lysyl hydroxylase deficiency is seen in type VI EDS, linked with severe kyphoscoliosis,retinal detachment and other eye abnormalities. Collagen V deficiencies are seen in type I (Gravis)and type II (Mitis) EDS, associated with skin elasticity, gaping wounds, hypermobile joints, Gorlin’ssign, blue sclera and mitral valve prolapse209) Anodontia is a bone finding seen in which of the following conditions:A. Tuberous sclerosis 70
  • 25. B. Letterer-Siwe diseaseC. Hyper-IgE syndromeD. Jackson Sertoli syndromeE. Hypomelanosis of ItoCorrect ChoiceHypomelanosis of Ito, or Incontinentia pigmenti achromians is a condition characterized by marble-cake hypopigmentation, epilepsy, alopecia, scoliosis and mental/motor retardation. Thecharacteristic dental abnormality is anodontia. The remaining syndromes are not associated withanodontia210) Multiple cylindromas and trichoepitheliomas are associated with which of the followingsyndromes?A. GardnerB. Cronkhite-CanadaC. Brook-SpieglerCorrect ChoiceD. CowdensE. Nicolau-BalusThese findings are characteristic of Brook-Spiegler syndrome. Gardner syndrome is associated withgastrointestinal carcinoma and adnexal neoplasms, Cronkhite-Canada syndrome, Nicolau-Balus andCowdens are not associated with cylindromas or trichoepitheliomas211) Which of the following features is not associated with Cornelia de Lange Syndrome?A. Normal intelligenceCorrect ChoiceB. Fifth finger clinodactylyC. Recurrent lung infectionsD. CryptorchidismE. Characteristic facies with downturned mouth, hirsutism, synophrys, trichomegaly, antevertednostrils, long philtrum and low set earsChildren with Cornelia de Lange are usually severly retarded with an IQ <35. In addition to thefeatures listed above, other features include cutis marmorata, hypoplastic nipples and umbilicus,low-pitched cry in infancy and congenital heart defects. While most cases are inherited in a sporadicmanner, those cases which are familial are thought to be autosomal dominant and associated withthe NIPBL (nipped-beta-like) gene. Prognosis is poor with premature death often secondary tosspiration or recurrent pulmonary infection212) Erythematous keratotic plaques of KID Syndrome most commonly occur in which location?A. ChestB. NeckC. BackD. FaceCorrect Choice 71
  • 26. E. AbdomenThe erythematous keratotic plaques of KID Syndome occur on face, extremities > trunk. KIDSyndrome is characterized by keratitis, icthyosis, and deafness. It is inherited in an autosomaldominant fashion and caused by a mutation in the GJB2 gene which encodes connexin 26213) Findings of milia, cylindromas and the condition shown in the pathology image arecharacteristic of which of the following syndromes?A. Brook-Spiegler syndromeB. Gorlins syndromeC. Rombo syndromeD. Rasmusen syndromeCorrect ChoiceE. Familial cylindromatosisRasmusen syndrome is characterized by milia, trichoepitheliomas and cylindromas. The otheroptions have trichoepitheliomas as a feature of the syndrome, but not with the other listed findings214) In addition to pheochromocytoma and medullary thyroid carcinoma and the skin finding in theimage in a patient with a marfanoid body habitus is associated with which of the followingsyndromes?A. MEN type IB. Basex syndromeC. Cowden syndromeD. MEN type IIaCorrect ChoiceE. MEN type IIbThe image show amyloidosis, which is found in addition to pheochromocytoma, medullary thyroidcarcinoma and parathyroid abnormalities in Sipple syndrome or MEN type IIa. Cowden disease isnot associated with any of the listed findings.215) Argininosuccinic aciduria is associated with a hair abnormality shown in the image. Which ofthe following hair finding is seen in these patients?A. Trichorrhexis nodosaCorrect ChoiceB. TrichoschisisC. Trichorrhexis invaginataD. Pili tortiE. None of these options are correctTrichorrhexis nodosa is shown in the figure and is found in ~50% of affected patients withargininosuccinic aciduria. Affected individuals will have short, broken scalp hairs, often increasedwith late onset disease. Usually these findings are increased in the occipital region of the scalp. Theremaining options are not found in affected individual216) The most common cutaneous association with monilethrix is: 72
  • 27. A. AtrophyB. EczemaC. HypopigmentationD. Keratosis PilarisCorrect ChoiceE. HyperpigmentationMonilethrix is an autosomal dominant condition which, by definition, presents with “beaded” hear.Clinically, patients present with short, sparse lusterless hair. Keratosis pilaris is the most commonassociated feature217) An infant with doughy, redundant skin and short sparse hairs is likely to show which featureson x-ray?A. OsteopoikilosisB. Sphenoid wing dysplasiaC. Stippled epiphysesD. Periosteal thickeningE. Metaphyseal widening in the long bonesCorrect ChoiceThe patient described has Menkes Kinky Hair syndrome, an X-linked recessive disease due to adefect in an intestinal copper transport protein. Clinical features include pili torti, short, brittle“steel-wool” hair, and spare eyelashes and sparse broken eyebrows. The skin is oftenhypopigmented with a soft, “doughy” consistency and redundancy. Musculoskeletal manifestationsinclude metaphyseal widening with spurs in the long bones218) Familial macular and lichen amyloidosis is a feature of which of the following conditions?A. Sipple syndrome Correct ChoiceB. Peutz-Jeghers syndromeC. Birt-Hogg-Dube syndromeD. Dyskeratosis congenitaE. Marfan syndromeSipple syndrome (MEN 2a) is caused by autosomal dominant mutations in the ret protooncogene.Patients develop parathyroid cancers, pheochromocytomas, and medullary cancer of the thyroidgland. Familial macular and lichen amyloidosis is also a feature of this syndrome219) Which of the following is a feature of Neurofibromatosis type II?A. Lisch nodulesB. Optic gliomasC. Juvenile posterior subcapsular lenticular opacities Correct ChoiceD. Congenital hypertrophy of the retinal pigment epitheliumE. Lester iris 73
  • 28. Neurofibromatosis type II is an autosomal dominant disorder caused by mutations in schwannomin/merlin. Clinical features include cutaneous schwannomas and neurofibromas, bilateral vestibularschwannomas, and juvenile posterior subcapsular lenticular opacities220) Findings of dysplastic nevi and melanoma inherited in an autosomal dominant fashion is linkedwith which of the following?A. Pancreatic malignancyCorrect ChoiceB. Renal cell carcinomaC. Breast malignancyD. Thyroid malignancyE. Colon carcinomaFamilial dysplastic nevi/melanoma syndrome is linked with increased risk of pancreatic cancers andastrocytomas. There are no reported increased risks for the other types of cancers listed221) Which gene is defective in Wiskott-Aldrich syndrome?A. NCF2B. NCF1C. WASCorrect ChoiceD. CYBBE. CYBAThe WAS gene is defective in Wiskott-Aldrich syndrome. WAS is an Arp2/3 complex interactingprotein. The remaining options are genes related to Chronic Granulomatous Disease and are notactive in the pathogenesis of Wiskott-Aldrich syndrome222) Refsum syndrome is due to a deficiency in phytanyl coenzyme A hydroxylase. Treatment forthis condition is:A. Diet low in green vegetables, dairy and ruminant fats Correct ChoiceB. No treatment is available at this timeC. Enzyme replacementD. Avoid phenylalanineE. Diet high in green vegetables, dairy and ruminant fatsTreatment is with a diet low in green vegetables, dairy and ruminant fats is the treatment of choicefor Refsum syndrome. Avoidance of specific amino acids is not helpful223) Dermatofibrosis lenticularis disseminata and osteopoikilosis are findings seen with mutationsof which of the following genes?A. Lysyl hydroxylaseB. Lysyl oxidase 74
  • 29. C. LEMD3Correct ChoiceD. Fibrillin 2E. ABCC6Buschke-Ollendorf syndrome is caused by a loss-of-function mutation in LEMD3224) An infant girl of short stature and shortened 4th and 5th metacarpals is being evaluated forcoarctation of the aorta and horseshoe kidneys. Physical examination most likely reveals:A. ArachnodactylyB. Webbed neckCorrect ChoiceC. HemangiomaD. Giant congenital melanocytic nevusE. AlopeciaTurner’s syndrome results from nondysjunction during gametogeneiss leading to the XO genotype.Clinical features include short stature, redundant neck folds/webbed neck, multiple pigmented nevi,low set hairline, triangular facies, low-set ears, ptosis, wide-set nipples, shortened 4th and 5thmetacarpals, hypoplasia of lymphatics, coarctation of the aorta, and horseshoe kidneys225) Mutations in nuclear lamins are associated with which clinical feature?A. LipomatosisB. SarcomasC. Aplasia cutis congenitaD. Lipodystrophy Correct ChoiceE. LymphedemaBernardinelli-Seip congenital lipodystrophy and familial partial lipodystrophy are caused bymutations in nuclear lamins. The former is characterized by generalized lipodystrophy and the latteris characterized by by partial lipodystrophy226) A patient presents with multiple tumors on the scalp with pathology shown. Which of thefollowing genes is most likely mutated?A. NEMOB. APCC. CYLDCorrect ChoiceD. SPINK5E. PTENThe pathology shown is that of a cylindroma. Multiple cylindromas of the scalp, associated witheccrine spiradenomas can occur in the autosomal dominant familial cylindromatosis sydrome. Theremaining genes are not associated with formation of cylindromas 75
  • 30. 227) The most common ocular association with cutis marmorata telangiectatica congenital is:A. CataractsB. RetinoblastomaC. GlaucomaCorrect ChoiceD. Corneal opacityE. Angioid streaksGlaucoma is the most common associated eye finding in CMTC patients. Glaucoma is also seen inpatients with neurofibromatosis type 1 and Sturge Weber patients228) The following enzyme defect is most commonly seen in CHILD Syndrome.A. 3-beta-hydroxysteroid isomeraseB. NAD oxido reductaseC. 3-beta-hydroxysteroid dehydrogenaseCorrect ChoiceD. Aryl sulfatase EE. DNA helicaseCHILD Syndrome is a X-linked dominant disorder characterized by unilateral ichthyosiformerythroderma, ipsilateral limb deformity, and ipsilateral organ hypoplasia. The most commom genedefect is NSDHL which encodes 3-beta hydroxysteroid dehydrogenase. EBP gene defects whichencode 3-beta-hydroxysteroid isomerase have been described, however this is the usual defect inConradi-Hunermann Syndrome. Aryl sulfatase E is mutated in X-linked recessive chondrodysplasiapunctata229) Which of the following syndromes demonstrate atrophoderma vermiculatum?A. All of these answers are correctCorrect ChoiceB. Nicolau-Balus SyndromeC. ROMBO SyndromeD. Tuzun SyndromeE. Braun-Falco-Marghescu SyndromeAll of the listed syndromes include atrophoderma vermiculatum as part of their constellation ofsymptoms. Atrophoderma vermiculatum is characterized by honeycomb pattern of atrophic scars onthe face. Tuzun Syndrome also has scrotal tongue. ROMBO has BCCs, milia, peripheral vasodilation,trichoepitheliomas. Nicolau-Balus has eruptive syringomas and milia. Braun-Falco-Marghescu haskeratosis pilaris and palmoplantar hyperkeratosis230) Which opthamologic disease is associated with this disorder?A. Posterior subcasular lentiular opacityB. CataractsC. GlaucomaCorrect Choice 76
  • 31. D. Ectopia lentisE. Retinitis pigmentosaSturge-Weber syndrome is a sporadic disease characterized by a capillary malformation in thetrigeminal distribution. Patients may have associated cerebral atrophy, vascular malformations ofthe leptomeninges, and seizures. All patients with Sturge-Weber should be referred to theopthamologist for glaucoma screening231) Ivory-colored papules between the angles of the scapulae are characteristic of whichsyndrome:A. ScheieB. MorquioC. HunterCorrect ChoiceD. HurlerE. SanfilippoThese syndromes are all mucopolysaccharidoses. These papules are characteristic of Huntersyndrome which is caused by a deficiency in iduronate sulfatase232) You receive a hospital consult from the gastroenterology service for a 42-year old woman withesophageal cancer. They would like your opinion on the yellow, thickened areas on her palms andsoles in areas of pressure. When you speak with her, she says that her father had similar problemsand it runs in her family. Which of the following is defective?A. Connexin 31B. Connexin 30.3C. TOC geneCorrect ChoiceD. PlakoglobinE. DesmoplakinThis case describes Howell-Evans syndrome. This AD syndrome characteristically has a PPK in areasof pressure, oral leukoplakia and esophageal carcinomas. Desmoplakin is defective in Carvajalsyndrome and plakoglobin in Naxos syndrome. Connexin 31 and 30.3 are linked toerythrokeratoderma variabilis, which includes a PPK, but not esophageal carcinoma233) Defects in Fibrillin 2 are linked with:A. Congenital contractural arachnodactylyCorrect ChoiceB. Lipoid proteinosisC. Arthrochalasis multiplex congenitaD. Occipital horn syndromeE. Cutis LaxaFibrillin 2 defects arelinked primarily with congenital contractural arachnodactyly. This syndrome isassociated with long limbs, arachnodactyly, scoliosis and crumpled ears. Occasionally, fibrillin 2 canbe associated with Marfan syndrome also. The other conditions are not linked to fibrillin mutations 77
  • 32. 234) A patient with multiple deeply pigmented papules has a skin biopsy which reveals anepitheloid blue nevus. The next appropriate step is:A. Order an echocardiogramCorrect ChoiceB. Refer to geneticsC. Schedule prophylactic excision of the lesionD. Begin a malignancy work-upE. Reassure the patient and follow up as neededEpithelioid blue nevi have been reported with and without association with cardiac myxomas as acomponent of the Carney complex (NAME/LAMB syndrome). Carney complex is an autosomaldominant disorder caused by mutations in PRKAR1A. Patients have cutaneous and atrial myxomas,blue nevi, ephelides, adrenocortical disease, and testicular tumors235) The nucleotide excision DNA repair pathway is defective in which diseaseA. Xeroderma pigmentosaCorrect ChoiceB. Bournevilles diseaseC. Severe combined deficiency syndromeD. Griscelli syndromeE. Sjogren-Larssen syndromeThe pathogensis of Xeroderma Pigmentosum shows mutations i genes encoding DNA repairenzymes, leading to defective DNA excision repair upon exposure to UV radiation (D). Severecombined deficiency syndrome-major defect in cell-mediated and humoral immunity; most lackantibody-dependentcellular cytotoxicity and natural killer cell function (thus (B) is incorrect). The pathogensis forGriscelli Syndrome is a mutation in gene encoding for myosin Va or RAB27 a (thus (C) is incorrect).Sjogren-Larsson Syndrome has mutations in the FALDH gene (thus (E) is incorrect). Bournevillessyndrome (AKA Tuberous Sclerosis) shows a mutation in either TSC1 ancoding hamartin or TSC2encoding tuberin (thus (A) is incorrect236) A child presenting with the scalp findings shown and a right arm hypoplasia would bediagnosed with which of the following syndromes?A. Barts syndromeB. ProgeriaC. Adams-Oliver syndromeCorrect ChoiceD. None of these options are correctE. Dunnigan syndromeAdams-Oliver syndrome is defined by aplasia cutis congenita (ACC) (shown in the image), usually ofthe midline scalp with limb hypoplasia. Barts syndrome also has ACC as a finding, but it is usuallypresent on the lower extremities and associated dominant dystrophic epidermolysis bullosa.Progeria is a premature aging syndrome associated with a lamin-A mutation. Dunnigan syndrome isalso known as Familial partial lipodystrophy and is associated with a mutation in the BSCL2 gene.Neither are associated with findings of ACC 78
  • 33. 237) Papillon-Lefevre and Haim-Munk syndromes have which of the following symptoms?A. PseudoainhumB. Esophageal cancerC. Eccrine syringofibradenomaD. Right-ventricular cardiomyopathyE. Periodontitis with tooth loss Correct ChoiceRight-ventricular cardiomyopathy is associated with Naxos syndrome, pseudoainhum is associatedwith Vohwinkel syndrome, esophageal cancer is associated with Howel-Evans syndrome, and eccrinesyringofibradenomas are associated with Schopf-Schulz-Passarge syndrome. Periodontitis with toothloss is associated with Papillon-Lefevre and Haim-Munk syndromes, which are caused by mutationsin Cathepsin C238) The development of which malignancy is most commonly associated with lymphomatoidpapulosis?A. non-Hodgkins lymphomaB. immunoblastic lymphomaC. mycosis fungoidesCorrect ChoiceD. Waldenstroms macroglobulinemiaE. multiple myelomaLymphomatoid papulosis is a recurrant eruption of unclear etiology characterized by the appearanceof red-brown papules and nodules which spontaneously disappear in 3 to 8 weeks. It is notable forhistologic features which suggest a CD30 positive malignant lymphoma. There is controversyregarding whether lymphomatoid papulosis (LyP) is a malignant, premalignant or benign condition.The disease may last from months to years and in up to 20% of patients, it may be preceded by,followed by, or associated with another type of cutaneous malignancy. Generally, this is mycosisfungoides, a CD30-positive large T-cell lymphoma or Hodgkins disease. Because of this potentialrisk, long-term follow-up of these patients is required.(Fitzpatricks Dermatology in General Medicine, 5th ed 1999 p1269)(Bolognia Dermatology 1st ed 2003, p1935-1937)239) Pseudoxanthoma elasticum (PXE) can be transmitted in an autosomal dominant, recessive orsporadic manner. Which of the following genes is mutated in PXE?A. Collagen IIIB. Collagen IC. ABCC6Correct ChoiceD. MAN1E. Collagen VABCC6 is mutated in PXE. Other findings include fragmented and calcified elastin in skin, eyes,arteries. There is the appearance of plucked chicken skin on the flexures and yellow papules on themucous membranes. Angioid streaks are present in the eye. Other findings include gastrichemorrhage and arterial disease. The others are not involved in PXE 79
  • 34. 240) Pili trianguli et canaliculi is characteristic of which of the following syndromes?A. Uncombable hair syndromeCorrect ChoiceB. Bjornstad syndromeC. Menkes kinky hair syndromeD. Nethertons syndromeE. Leiners diseaseUncombable hair syndrome is characterized by pili trianguli et canaliculi. On examination of the hair,it is triangular with a canal-like groove runs along the shaft. The clinical findings are that of blond,shiny, "spun glass" hair. It is an autosomal dominant syndrome with no known gene locus. Theremaining syndromes do not have this hair finding present241) A BSCL2 gene mutation with the cutaneous findings of generalized lipodystrophy,hyperlipemia, hepatomegaly, acanthosis nigricans, elevated basal metabolic rate and non-ketoticinsulin resistant diabetes mellitus are characteristic of which of the following syndromes?A. None of the answers are correctB. Familial partial lipodystrophyC. All of the answers are correctD. Bjornstad syndromeE. Berardinelli-Seip congenital lipodystrophyCorrect ChoiceBerardinelli-Seip congenital lipodystrophy is described above. Familial partial lipodystrophy ischaracterized by a defect in LMNA and has symmetric lipoatrophy of trunk and limbs with sparing ofneck, shoulders, buffalo hump area and genitalia, tuboeruptive xanthomas, acanthosis nigricans andhypertriglyceridemia. Bjornstad syndrome is characterized by pili torti and deafness242) Collagen III is mutated in which type(s) of Ehlers-Danlos syndrome (EDS)?A. Periodontitis (type VIII)B. None of the answers are correctC. Vascular (type IV)D. Benign Hypermobile (type III)E. All of the answers are correctCorrect ChoiceCollagen III is mutated in all three types of EDS listed. Benign hypermobile type EDS is associatedwith hypermobile joints and is autosomal dominant (AD) in transmission. Vascular type EDS isassociated with arterial and visceral rupture leading to early death, and visible venous patterns. It istransmitted autosomal recessive (AR) or AD. Periodontitis type EDS is associated with mild EDSsymptoms and periodontitis243) What is the classic radiologic findings associated with this disorer?A. Calcifications of the falx-cerebri 80
  • 35. B. Osteopatha striataC. Dural calcificationsD. OsteopoikilosisE. Tram-track calcifications of the temporal and occipital cortexCorrect ChoiceSturge-Weber syndrome is a sporadic disroder characterized by a facial capillary malformation in atrigeminal nerve distribution. Patients with Sturge-Weber may have cerebral atrophy, ipsilateralvascular malformations of the leptomeninges, seizures, and glaucoma. The classic radiologic findingis tram-track calcifications of the temporal and occipital cortex244) Findings of eyelid papules (string of pearls) and a hoarse cry in infants is characteristic ofwhich of the following syndromes?A. AmyloidosisB. Pseudoxanthoma elasticumC. None of these answers are correctD. Lipoid proteinosisCorrect ChoiceE. Disseminated xanthomasFindings of the eyelid string of pearls and a hoarse cry during the first years of life (due to vocalcord infiltration) is characteristic of Lipoid Proteinosis (AKA Urbach-Wiethe disease or Hyalinosiscutis et mucosae). It is an autosomal recessive condition with mutations in the extracellular matrixprotein 1 gene. Other findings include calcifications of the temporal lobe and hippocampus, hairloss,atrophic scars and waxy papules on the face, verrucous nodules and a thick tongue. The otherconditions could be considered on the differential for Lipoid Proteinosis, but do not have the findingsdescribed above245) A 12 year-old boy with pits on his palms and lateral fingers may have:A. Secondary syphilisB. A corynebacteria infectionC. A hereditary keratodermaD. Arsenic exposureE. An inherited cancer syndromeCorrect ChoiceBasal cell nevus syndrome is an autosomal dominant disease caused by mutations in the PTCH1gene. Clinically, patients may have numerous basal cell carcinomas, palmoplantar pits, jaw cysts,frontal bossing, bifid ribs, calcification of falx cerebri, medulloblastoma, ovarian fibromas andfibrosarcomas246) A patient with colon cancer is diagnosed with Muir-Torre syndrome. Which of the followingcutaneous lesions might the patient have?A. TricholemmomasB. Basal cell carcinomasC. Seborrheic keratoses 81
  • 36. D. Keratoacanthomas Correct ChoiceE. Arsenical keratosesMuir-Torre syndrome is an autosomal dominant disease caused by mutations in MSH2 and MSH1,DNA mismatch repair genes. Clinically, patients have multiple sebaceous tumors (adenomas aremost common), keratoacanthomas, and are at risk for adenocarcinoma of the colon247) A patient with multiple sebaceous adenomas should be screened with which of the followingexaminations?A. Colonoscopy Correct ChoiceB. Retinal examinationC. Renal ultrasoundD. MRI of the spineE. LaryngoscopyMuir-Torre syndrome is an autosomal dominant disorder caused by the HMSH2 and MLH1 DNAmismatch repair genes. Clinically, there are numerous sebaceous adenomas, epitheliomas andcarcinomas and multiple keratoacanthomas associated with indolent colon and other visceraladenocarcinomas. Patients and first-degree relatives should be screened by colonoscopy as colonicadenocarcinomas may precede the development of cutaneous tumors248) “Coast of Maine” café au lait macules are characteristic of which conditionA. Hypomelanosis of ItoB. McCune-Albright syndrome Correct ChoiceC. Tuberous sclerosisD. Carney complexE. Gaucher’s syndromeMcCune-Albright syndrome is a sporadic condition caused by somatic mutations in the Gs subunit ofadenylate cyclase. Key clinical features include “coast of Maine” café au lait macules, polyostoticfibrous dysplasia, and precocious puberty.249) Patients with junctional epidermolysis bullosa have been found to have mutations in:A. All of the answers are correctCorrect ChoiceB. laminin 5C. collagen 17D. bullous pemphigoid antigen 2E. BP180All of the answers are correct. Laminin 5 is a protein integral in the adhesion of the dermis to theepidermis. Also involved in junctional epidermolysis bullosa is bullous pemphigoid antigen 2,collagen 17 and BP180, which are synonymous for the same structure 82
  • 37. 250) Which of the following eye findings is caused by the rupture of Bruchs membrane?A. Angioid streaksCorrect ChoiceB. Blue scleraeC. KeratoconusD. Ruptured globeE. Retinal detachmentThe rupture of Bruchs membrane causes angioid streaks in pseudoxanthoma elasticum. Bruchsmembrane is the innermost layer of choroid with a central layer of elastic fibers. The other findingsare found in Ehlers-Danlos syndrome and are not related to Bruchs membrane251) A 5 month old girl presents with failure to thrive. She has had life-long atopic dermatitistreated with topical hydrocortisone cream and has persisent hypernatremia. On your exam, she hasgeneralized erythema and scaling of her body and trichorrhexis invaginata on examination of hairsfrom her eyebrows. Which syndrome is she most likely to have?A. Netherton SyndromeCorrect ChoiceB. Omenn SyndromeC. Severe atopic dermatitisD. Wiskott-Aldrich SyndromeE. Leiner syndromeNetherton syndrome is caused by a mutation in the SPINK5 gene, encoding LEKT1. This is a serineprotease inhibitor which is important in downregulating inflammation. Early presentation is withfailure to thrive, generalized erythema/scale, hypernatremia, and sparse hair with the characteristicfinding of trichorrhexis invaginata. Pili torti and trichorrhexis nodosa also can be seen. Eyebrow hairis most commonly affected. Omenn syndrome is an autosomal recessive form of severe combinedimmunodeficiency (SCID) with findings of failure to thrive, erythroderma, scaling, chronic diarrhea,lymphadenopathy, and hepatosplenomegaly. Leiner syndrome can present with failure to thrive,immunodeficiency and seborrheic dermatitis. Wiskott-Aldrich syndrome is an x-linked recessivecondition with mutations of the WAS gene. Presentation includes atopic dermatitis,thrombocytopenia, recurrent bacterial infection, lymphoreticular malignancy with non-Hodgkinslymphoma being the most common, and increased IgA, D and E. With the characteristic hairchanges, atopic dermatitis alone is not the most likely diagnosis252) Patients with hemochromatosis are at increased risk for which of the following?A. PolyarthritisB. Yersenia infectionsC. Vibrio vulnificus infectionsD. Generalized metallic-grey hyperpigmentationE. All of these options are correctCorrect ChoicePatients with hemochromatosis have increased intestinal iron absorption leading to systemic ironoverload. Signs inclued a generalized metallic-grey hyperpigmentation, koilonychia, alopecia(especially pubic/axillary hair) cardiac failure/arrythmias/heart block, hepatomegaly with crrhosis,diabetes (bronze diabetes), polyarthritis with chondrocalcinosis and are susceptible to Vibriovulnificus and Yersinia infections 83
  • 38. 253) The diagnostic test for chronic granulomatous disease is:A. Bone marrow biopsyB. Histamine skin testC. Potassium hydroxideD. Nitroblue tetrazolium reduction assayCorrect ChoiceE. Dimethylglyoxime testChronic granulomatous disease is characterized by a defect in the ability to kill catalase positiveorganisms within phagocytic leukocytes. This results from a neutrophilic defect in the cytochromefound in the NADPH oxidative pathway responsible for a respiratory burst. The nitroblue tetrazolium(NBT) reduction assay demonstrates the leukocyes’ ability to reduce the dye and produce a bluecolor change. Patients with chronic granulomatous disease are unable to redue the dye254) A 50 year man presents with generalized metallic-grey hyperpigmentation. His past medicalhistory includes diabetes, hepatomegaly and arrythmias. Laboratory tests should include:A. Iron levelsCorrect ChoiceB. Arsenic levelsC. Copper levelsD. Lead levelsE. Cyanide levelsHemochromatosis is an autosomal recessive disease resulting in increased intestinal iron absorptionand iron deposition in a variety of organs. Clinical features include generalized metallic-greyhyperpigmentation, koilonychia, sparse or absent hair, hepatomegaly, cardiac failure/arrhythmias,insulin-dependent diabetes, hypogonadism and polyarthritis255) Which of the following conditions is worsened by ingestion of lithium?A. Darier’s DiseaseCorrect ChoiceB. Hereditary lymphedema (Nonne-Milroy disease)C. Hailey-Hailey DiseaseD. Haim-Munk syndromeE. Epidermolytic hyperkeratosisPatients with Darier’s disease should not be treated with lithium due to its worsening or in somecases unmasking the disease. The mechanism for this is not known. Lithium treatment does notworsen the other listed conditions256) Which of the following is caused by a defect in keratins 4 & 13?A. Epidermolysis bullosa simplexB. Epidermolysis bullosa simplex with myotonic dystrophy 84
  • 39. C. Junctional EB with pyloric atresiaD. White sponge nevusCorrect ChoiceE. Clouston’s syndromeWhite sponge nevus is caused by a defect in keratins 4 & 13.The remaining entities have the corresponding defects:EB simplex—keratins 5 & 14EB simplex with myotonic dystrophy—plectinJunctional EB with pyloric atresia—Integrin ?-6, ?4Clouston’s syndrome (hidrotic ectodermal dysplasia)—connexin 30.257) The main cause of death in patients with dyskeratosis congenita is which of the following?A. LeukemiaB. Pancytopenia Correct ChoiceC. Oral squamous cell carcinomaD. Atherosclerotic heart diseaseE. Renal cell carcinomaDyskeratosis congenita is usually inherited in an X-recessive fashion due to mutations in thedyskerin gene, which is involved in ribosomal RNA synthesis. The less common autosomal dominantform is caused by mutations in the telomerase gene. Clinically, there is reticulated pigmentation ofskin, poikiloderma, alopecia, nail atrophy, premalignant oral leukoplakia, and Fanconi-typepancytopenia resulting in early death258) Which of the following is NOT a characteristic skin finding in patients with Down Syndrome?A. Elastosis perforans serpiginosaB. SyringomasC. Flat nipplesD. Single palmar creaseE. Small tongueCorrect ChoiceDown syndrome is caused by nondisjunction and results in trisomy 21. Clinical features includesingle palmar crease, flat nipples, increased nuchal skin folds, syringomas, elastosis perforansserpiginosa, xerosis, epicanthic folds of eyes, protruding scrotal tongue and fissured thickened lips.259) Which vascular disorder is characterized by facial vascular malformation and ipsilateralintracranial and retinal arteriovenous malformations(AVMs)?A. Encephalotrigeminal angiomatosisB. Von Lohuizen’s diseaseC. PHACESD. Bonnet Dechaune Blanc syndromeCorrect ChoiceE. Sturge-Weber syndome 85
  • 40. Bonnet Bechaune Blanc syndome, also know as Wyburn-Mason syndrome, is characterized by afacial vascular malformation and ipsilateral intracranial and retinal AVMs. Encephalotrigeminalangiomatosis is another name for Sturge-Weber. Von Lohuizens disease is another name for cutismarmorata telangiectatica congenita260) The syndrome characterized by generalized mild hyperkeratosis, erythematous keratoticplaques, palmoplantar keratoderma, non-progressive sensorineural deafness, progressive bilateralkeratitis with secondary blindness is:A. Vohwinkel syndromeB. CHILD syndromeC. KID syndromeCorrect ChoiceD. Refsum syndromeE. Erythrokeratoderma variabilisKID syndrome is described above. It is an autosomal dominant mutation in connexin 26. Vohwinkelsyndrome is also a connexin 26 mutation, but is characterized by diffuse honeycombedpalmoplantar keratoderma, pseudoainhum, starfish-shaped keratotic plaques over joints anddeafness. Erythrokeratoderma variabilis is an autosomal dominant mutation in connexin 31 and30.3 characterized by erythematous migratory patches, fixed hyperkeratotic plaques and apalmoplantar keratoderma. CHILD syndrome is an X-linked dominant mutation condition due to amutation in NAD(P)H Steroid dehydrogenas-like protein, lethal in males. Unilateral ichthyosiformerythroderma, limb/visceral hypoplasias are characteristic. Refsum syndrome is an autosomalrecessive condition with a mutation in phytanoyl coenzyme A hydroxylase characterized by mildichthyosis, cerebellar ataxia, peripheral neuropathy, retinitis pigmentosa (salt & pepper) anddeafness261) The most common cardiovascular defect in patients with Noonan syndrome is:A. Ventricular septal defectB. Aortic stenosisC. Atrial septal defectD. Enlarged aortaE. Pulmonic valve stenosisCorrect ChoiceNoonan’s syndrome is also known as cardiofaciocutaneous syndrome. Patients have short stature,ptosis, hypertelorism, low-set ears, thick lips and curly hair. Pulmonic valve stenosis is the mostcommon cardiovascular defect, with atrial septal defects also common262) What nail change is seen in patients with Mal de Meleda Syndrome?A. leukonychiaB. pterygiumC. KoilonychiaCorrect ChoiceD. Longitudinal ridgingE. Onycholysis 86
  • 41. Mal de Meleda is an autosomal recessive disease characterized by transgedient malodorous PPK,hyperhidrosis, keratotic plaques at knees and elbows, subungual hyperkeratosis, and koilonychia.The gene defect is SLURP 1263) Which of the following laboratory test might prove useful in the diagnosis of Fabry disease:A. Stool guaiacB. Bleeding timeC. Fasting lipidsD. Urinary sediment exam with polarizing light microscopyCorrect ChoiceE. Complete blood count with differentialPatients with Fabry disease have a defect in the alpha-galactosidase A enzyme, leading to anaccumulation of glycosphingolipids in all tissues. Although patients are at increased risk formyocardial infrctions and strokes, the serum lipid levels are normal. Ischemic events occur as aresult of glycosphingolipid accumulation in endothelial cells leading to swelling. In the brain, strokesoccur from direct vessel occlusion or stretching and distention of branches of dolichoectatic parentvessels. Deposits in the kidneys leads to progressive renal failure with urine exam exhibitingproteinuria and birefringent lipid globules (“maltese crosses”) seen with polarizing light microscopy264) The x-linked recessive type of dyskeratosis congenita is:A. PTENB. dyskerinCorrect ChoiceC. CDKN2AD. MeninE. TERCThe dyskerin gene, whose product is involved in ribosomal RNA synthesis, is mutated in X-linkedrecessive dyskeratosis congenita. TERC is linked with autosomal domininant transmission of thesyndrome. CDKN2A is involved in familial dysplastic nevi/melanoma syndrome, PTEN in Cowdensyndrome and Menin in MEN type I265) Which of the following conditions is inherited in an X-linked recessive manner?A. Sjogren-Larsson syndromeB. Ichthyosis vulgarisC. Wiskott-Aldrich SyndromeCorrect ChoiceD. Epidermolysis bullosa simplexE. Netherton’s SyndromeWiskott-Aldrich Syndrome is inherited in an X-linked recessive manner. Epidermolysis bullosasimplex and ichthyosis vulgaris are inherited in an autosomal dominant (AD) manner. Sjogren-Larsson and Netherton’s syndrome are inherited in an autosomal recessive manner 87
  • 42. 266) What is this syndrome which is histologically characterized by widely dispersed granularmaterial amidst normal fibers?A. Focal Dermal HypoplasiaB. Pseudoxanthoma ElasticumCorrect ChoiceC. Buschke-Ollendorf SyndromeD. Lipoid ProteinosisE. Ehlers Danlos SyndromePseudoxanthoma elasticum is genodermatosis characterized by redundant skin, angioid streaks,yellow papules on the mucous membranes and bleeding from gastric artery. On histology, readilyapparent denerative changes of the elastic fibers are prominent, even without special stains267) The most common neoplasm seen in Maffucci Syndrome is:A. EnchondromasCorrect ChoiceB. AngiosarcomasC. chondrosarcomaD. LymphangiosarcomasE. OsteosarcomasMaffucci syndrome comprises of superficial and deep venous malformations, enchondromas, andshort stature. Enchondromas are the most common neoplasm, while chondrosarcomas are the mostcommon malignancies268) Which of the following syndromes is X-linked dominant?A. X-linked icthyosisB. anhidrotic ectodermal dysplasiaC. dyskeratosis congenitaD. Menkes kinky hair syndromeE. orofaciodigital syndrome 1Correct ChoiceOrofaciodigital sydrome 1 is an X-linked dominantly inherited disorder caused by a defect in theCXORF5 gene. The rest of the above conditions are inherited in an x-linked recessive pattern.269) Which malignancy is seen in approximately 15-20% of people with the disease characterizedby a defect in a parathyroid hormone receptor protein?A. osteosarcomaB. chondrosarcomaCorrect ChoiceC. angiosarcomaD. rhabdomyosarcomaE. epitheliod sarcoma 88
  • 43. Approximately 15-20% of patients with Maffuccis syndrome will develop chondrosarcoma.Maffuccis syndrome is due to a defect in a parathyroid hormone receptor protein270) Medulloblastoma is seen in which syndrome?A. Basal cell nevus syndromeCorrect ChoiceB. Gardner’s syndromeC. Multiple endocrine neoplasia 2bD. Muir-Torre syndromeE. Neurofibromatosis Type 1Basal cell nevus syndrome is an autosomal dominant syndrome caused by a mutation in PTC gene,which acts in the Sonic hedgehog pathway. Cutaneous manifestations of this genodermatosisinclude basal cell carcinomas, palmoplantar pits, epidermoids cysts. Other findings includeodotogenic cysts, frontal bossing, bifid ribs, calcification of the falx cerebri and medulloblastomas271) A 2 year old girl presents with sunken eyes, large ears, microcephaly and a photodistributederuption on her face. Eye exam reveals “salt and pepper” retina. The gene responsible for thissyndrome codes for a:A. Transcription factorB. DNA helicaseCorrect ChoiceC. Lysosomal proteaseD. Surface glycoproteinE. Mismatch repair geneThe patient described has Cockayne syndrome, an autosomal recessive disorder believed to be dueto a mutation in either DNA helicase or defective nucleotide excision repair. UV irradiated cells havedecreased DNA and RNA synthesis and increased chromosomal breaks. Clinical features includecachectic dwarfism with microcephaly, thin nose, large ears, photosensitive eruption, cataracts, salt& pepper retina, and diffuse demyelination272) Which of the following findings is characteristic of a mutation in lamin A?A. Lipoatrophic sclerodermoid skinB. All of the answers are correctCorrect ChoiceC. Craniomegaly with small faceD. Severe premature atherosclerosis with early deathE. AlopeciaA mutation in Lamin A causes Progeria (Hutchinson-Gilford syndrome). Other findings include nailatrophy and muscle/bone wasting. Presentation is in the first or second year of life. An increasedurine hyaluronic acid can be helpful in diagnosis273) Which disease is found more commonly in mothers of patients with chronic granulomatousdisease? 89
  • 44. A. Erythema nodosumB. SarcoidosisC. Discoid lupus erythematousCorrect ChoiceD. Wegeners diseaseE. Churg-Straus diseaseFemale carriers of chronic granulomatous disease have an increase incidence of discoid lupus,infections and apthous stomatitis274) Osteopathia striata is seen in which of the following disorders?A. Aplasia cutis congenitaB. SclerodermaC. Focal dermal hypoplasia Correct ChoiceD. Albright’s syndromeE. Gaucher’s diseaseFocal dermal hypoplasia (Goltz syndrome) is an X-linked dominant disorder that is lethal in males.There is linear atrophy following Blaschko’s lines with areas of fat herniation with underlyingosteopathia striata, which is radiologically characterized by linear bony hyperdensity. Other featuresinclude mucocutaneous papillomas and pits, alopecia, nail dystrophy, tooth abnormalities, andcolobomas275) Xeroderma pigmentosum (XP) variant is different than classic XP in which of the followingway?A. Increased chromosomal breakage and sister chromatid exchangesB. Defective DNA nucleotide excision repair of the global genomeC. Defective DNA nucleotide excision repair of actively transcribing genesD. Defective post-replication repairCorrect ChoiceE. Low IgMXP variant is DNA nucleotide excision repair proficient, but the defect is in post replication repair ofDNA. Increased chromosomal breakage and sister chromatid exchanges is found in Bloom’ssyndrome, an autosomal recessive syndrome caused by a defect in BLM gene, whose productfunctions as a helicase. Clinical findings include: Telangiectasias, short stature, malar erythema,recurrent infection, increased frequency of leukemia and lymphoma, normal intelligence. DefectiveDNA nucleotide excision repair of actively transcribing genes is a feature of Cockayne’s syndrome,an autosomal recessive syndrome with clinical findings including: Cachexia, short stature,pigmentary retinal degeneration, progressive deafness and no increase in neoplasms. Xerodermapigmentosum has seven different complementation groups (A-G), each associated with a differentform of impairment of DNA nucleotide excision repair276) A child presents with sparse, short hair and sensorineural deafness. On microscopicexamination of the hair, pili torti is noted. Which of the following syndromes is the most likelydiagnosis?A. None of the options are correct 90
  • 45. B. Menkes kinky hair syndromeC. Bjornstad syndromeCorrect ChoiceD. Argininosuccinic aciduriaE. TrichothiodystrophyBjornstad syndrome is the most likely diagnosis. This rare syndrome (~25 cases) is autosomalrecessive. Findings are of deafness and pili torti. The most common hair finding in Menkessyndrome is pili torti, but it is not associated with hearing loss. Argininosuccinic aciduria isassociated with trichorrhexis nodosa and has no associated hearing loss277) Which genetic defect could explain these cutaneous findings in addition to abnormalimmunoglobulin levels, recurrent respiratory infections, hypogonadism, and an increased risk ofleukemia and lymphoma?A. Adenosine deaminaseB. ERCC6C. WAS geneD. RecQL3Correct ChoiceE. NADPH oxidaseBlooms syndrome is an autosomal recessive disorder caused by mutations in the RecQL3 geneencoding a DNA helicase. Clinically, individuals with Blooms syndrome have a photodistributederythema with telangectasia on the malar eminences. The may also have decreased IgM and IgAlevels, hypogonadism, and an increased risk for leukemia and lymphoma278) A patient with multiple lentigines and blue nevi may also have:A. mental retardationB. deafnessC. atrial myxomaCorrect ChoiceD. pulmonary valve stenosisE. GI malignancyThis patient may have a constellation of features associated with NAME syndrome, otherwise knownas Carney complex or LAMB syndrome. This condition is inherited in an autosomal dominant patternand is due to a defect in the PRKAR1A gene. This condition is characterized by the followingfeatures: blue Nevi, Atrial myxomas, cutaneous Myxomas, and Ephelides. In addition, testiculartumors are seen as well as sexual precocity. Finally, patients may have endocrine abnormalitiesincluding pigmented nodular adrenocorticoal disease and Cushing syndrome as well as pituitaryadenomas. Deafness, pulmonary stenosis, GI malignancies, and mental retardation are not featuresof this condition.(Spitzs Genodermatoses. 1996, p70-71)(Abdelmalek, N. J Am Acad Dermatol 2002;46:161-183).279) Ehlers-Danlos Syndrome with congenital adrenal hyperplasia is caused by mutations affectingwhich of the following? 91
  • 46. A. FibronectinB. Lysyl oxidaseC. Lysyl hydroxylaseD. Tenascin-X Correct ChoiceE. Collagen 5Ehlers-Danlos Syndrome type with congenital adrenal hyperplasia is caused by mutations intenascin-X280) Which of the following diseases is seen only in females?A. Hypomelanosis of ItoB. Carney complexC. PiebaldismD. Griscelli syndromeE. Incontinentia pigmenti Correct ChoiceIncontinentia pigmenti (Bloch-Sulzberger syndrome) is an X-linked dominant disease that is lethal inmales. There are four stages: vesicular, verrucous, hyperpigmented and hypopigmented. Also seenare peg and conical teeth, eye abnormalities, CNS defects, and alopecia. This condition is caused bymutations in the NEMO gene281) Which of the following is caused by a defect in cathepsin C?A. Muir-TorreB. Nail-Patella syndromeC. Rubenstein-TaybiD. Papillon-LefevreCorrect ChoiceE. Bullous Icthyosis of SiemensPapillon-Lefevre is a palmoplantar keratoderma caused by a mutation in chromosome 11q14,leading to a defect in Cathepsin C, a lysosomal enzyme. Clinical manifestations of papillon lefevreinclude sharply demarcated palmoplantar keratoderma with extension to dorsal surface(transgrediens), spare hair, periodontitis, and pyoderma282) Which of the following syndromes is characterized by follicular atrophoderma, hypohidrosis,hypotrichosis and multiple basal cell carcinomas?A. Bazex syndromeCorrect ChoiceB. Rombo syndromeC. Incontinentia PigmentiD. Rasmusen syndromeE. Gorlin syndromeBazex syndrome has the findings of follicular atrophoderma, hypohidrosis, hypotrichosis andmultiple basal cell carcinomas (BCC). Rombo syndrome is associated with BCC and hypotrichosis, 92
  • 47. but not the other listed findings. The atrophoderma in Rombo syndrome is vermicular, not follicular.Rasmusen syndrome is not associated with BCC283) Patients with x-linked icthyosis are more prone to getting which two malignancies?A. Renal cell and ALLB. Testicular and AMLC. Pancreatic and acute myelogenous leukemia (AML)D. Testicular and ALLCorrect ChoiceE. Pancreatic and acute lymphocytic leukemia (ALL)Patients with x-linked icthyosis have a 20% chance of having cryptorchidism and are more prone toboth testicular cancer and acute lymphocytic leukemia284) Odontogenic cysts and palmoplantar pits are seen in:A. Bloom’s SyndromeB. Refsum syndromeC. Gorlin SyndromeCorrect ChoiceD. Gardner’s syndromeE. Goltz SyndromeGorlin syndrome (Basal Cell Nevus Syndrome)is an autosomal recessive disorder due to a defect inthe PTCH gene whose function normally inhibits “SMOOTHENED” signaling. Odontogenic cysts andpalmoplantar pits are characteristic features, in addition to multiple basal cell carcinomas. Otherfeatures include: frontal bossing, kyphoscoliosis, calcification of falx cerebri, hypertelorism, ovarianfibromas and rarely mental retardation285) Comma shaped corneal opacities are seen in what disease?A. Refsum SyndromeB. Proteus syndromeC. Sjogren-Larson SyndromeD. X-linked ichthyosisCorrect ChoiceE. Pseudoxanthoma elasticumX-linked ichthyosis is a X-linked recessive disorder secondary to steroid sulfatase deficiencycharacterized by brown adherent scale. Additional findings include comma-shaped corneal opacities,cryptorchisdism, and failure to progress during labor.286) Which of the following is caused by a mutation in a gene that leads to defective NF-KBactivation?A. Vohwinkel’sB. MEN IIa 93
  • 48. C. Chediak-HigashiD. Incontinentia pigmentiCorrect ChoiceE. PiebaldismIncontinential pigmenti is an X-linked dominant disorder caused by a mutation in the NEMO genelocated at Xq28. NEMO is an NF-KB modulator. A genetic defect in NEMO leads to defectiveactivation of NF-KB (a transcription factor). MEN IIa is caused by a mutation in the RET proto-oncogene, piebaldism is caused by the C-kit protocogene, chediak-higashi is caused by a mutationin lysosomal tracking, and Vohwinkel’s is caused by a defect in the loricrin gene, which codes for astructural protein287) Giant lysosomal granules are seen in which disease?A. Griscelli syndromeB. PiebaldismC. Incontinentia pigmentiD. Carney complexE. Chediak-Higashi syndrome Correct ChoiceChediak-Higashi syndrome is caused by an autosomal recessive mutation in a lysosomal transportgene (LYST, CHS1). This disorder is characterized by oculocutaneous albinism, ataxia, muscleweakness, and giant lysosomal granules. There is an accelerated phase characterized bylymphohistiocytic infiltration of reticuloendothelial system, pancytopenia and death 94