ETAS_MCQ_03 a genodermatoses


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ETAS_MCQ_03 a genodermatoses

  1. 1. Genodermatoses1) Tyrosinase positive albinism (oculocutaneous albinism type 2) is caused by a mutation in whichof the following:A. TyrosinaseB. C-kitC. NEMOD. Tyrosinase related protein 1E. P gene Correct ChoiceOculocutaneous albinism (OCA) type 1 (Tyrosinase negative albinism) is caused by mutations in thetyrosinase gene. OCA type 2 (tyrosinase positive albinism) is caused by mutations in the P gene.OCA type 3 is caused by mutations in the tyrosinase related protein 1 gene. C-kit mutations causepiebaldism and NEMO mutations cause incontinentia pigmenti.2) A patient with a port wine stain covering one enlarged leg likely has which of the followingassociated symptoms?A. EnchondromasB. Visceromegaly with omphaloceleC. DistichiasisD. Lymphatic and deep venous insufficiency Correct ChoiceE. Bilateral retinal hemangioblastomasKlippel-Trenaunay-Weber syndrome is a sporadic condition characterized by port-wine stainstypically covering one lower extremity that is enlarged with underlying lymphatic and deep venousinsufficiency.3) Patients with Hermansky-Pudlak syndrome may experience which of the following systemiccomplications as a result of their disease?A. Aortic stenosisB. Rectal abscessesC. Arteriovenous malformationsD. Gastroesophageal reflux diseaseE. Pulmomary fibrosisCorrect ChoicePatients with Hermansky-Pudlak syndrome are tyrosinase positive albinos. In addition to theirpigmentary dilution and increased risks for cutaneous malignancies, patients lack platelet granulesleading to impaired platelet aggregation (and therefore a bleeding diathesis). There is also alysosomal membrane defect which leads to the accumulation of ceroid lipofuscion in macrophageswithin the lung (leading to pulmonary fibrosis), gastrointestinal tract (leading to granulomatouscolitis), and heart (cardiomyopathy).4) Non-bullous icthyosiform erythroderma is caused by which of the following mutationsA. 12R-lipoxygenase gene (ALOX12B)B. lipoxygenase-3 gene (ALOXE3)C. All of these answers are correctCorrect ChoiceD. transglutaminase-1 gene (TGM1) 1
  2. 2. E. Both 12R-lipoxygenase gene (ALOX12B) and lipoxygenase-3 gene (ALOXE3) are correctNon-bullous congenital erythroderma (NCIE)is an autosomal recessive disorder characterized by acollodion baby presentation at birth, and generalized erythroderma with fine white scale,palmoplantar keratoderma, and heat intolerance. NCIE may be caused by mutations intransglutaminase-1 gene (TGM1), the 12R-lipoxygenase gene (ALOX12B), and the lipoxygenase-3gene (ALOXE3). Mutations in the keratinocyte TGM1 gene interferes with normal cross-linking ofstructural proteins and the lipid envelope, leading to defective cornification and desquamation.ALOXE3 functions as an epoxy alcohol synthase using the product of ALOX12B as the preferredsubstrate; either gene can be the site of mutations causing NCIE.5) In which of the following Genodermatoses would one find cutaneous hyperpigmentation, bluelunulae and Kayser-Fleishcher ringsA. HemochromatosisB. Osteogenesis ImperfectaC. Marfans DiseaseD. Gauchers DiseaseE. Wilsons DiseaseCorrect ChoiceIn Wilsons disease (Hepatolenticular Degeneration) one will find a vague greenish discoloration ofthe skin on the face, neck, and gentalia Hyperpigmentation), azure lunulae (sky-blue moons) of thenails, and Kayser-Fleischer rings. This is due to the body retaining excessive amounts of copper6) Christ-Siemens-Touraine Syndrome is most commonly linked with defects in which of thefollowing genes?A. ectodysplasin (EDA)Correct ChoiceB. ERCC2C. NEMOD. None of these options are correctE. ATP7AEctodysplasin (EDA) on Xq12-q13 is transmitted in an X-linked recessive fashion and is the mostcommon cause of anhidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome orhypohidrotic ectodermal dysplasia). NEMO can be linked to this syndrome and is associated withimmunodeficiency, but this is a rare association. ERCC2 is associated with trichothiodystrophy andATP7A with Menkes kinky hair syndrome. They are not associated with anhidrotic ectodermaldysplasia.7) Cronkhite-Canada is associated with gastrointestinal polyposis, nail atrophy, alopecia,generalized pigmentation of skin and melanotic macules on the fingers. Which of the followingdescribes its inheritance pattern?A. X-linked dominantB. X-linked recessiveC. Autosomal recessiveD. Autosomal dominantE. SporadicCorrect ChoiceCronkhite-Canada is associated with gastrointestinal polyposis, nail atrophy, alopecia, generalizedpigmentation of skin and melanotic macules on the fingers. It is inherited in a sporadic manner. 2
  3. 3. 8) A biopsy is taken from a patient with multiple facial lesions is shown. They also have oralpapillomas and acral keratotic papules. Which of the following genes is most likely involved in theetiology of these lesions?A. CDKN2AB. PTENCorrect ChoiceC. NCF1D. NCF2E. CYBAThe biopsy shown is a trichilemmoma. Patients with Cowden syndrome (multiple hamartomasyndrome) will have multiple facial trichilemmomas in addition to the other findings mentioned. Alsopresent are multiple other adenomas and potentially adenocarcinomas, especially of the thyroid andbreast. Hamartomatous polyps of the gastrointestinal tract are also present.The other listed genes are not involved in Cowden syndrome. CYBA, NCF1/2 are involved in chroincgranulomatous disease and CDKN2A is associated with familial dysplastic nevi.9) Ectopia lentis (downward displacement of the lens) is characteristic of:A. Multiple Carboxylase deficiencyB. HomocystinuriaCorrect ChoiceC. Ehlers-Danlos syndromeD. PhenylketonuriaE. Marfan syndromeEctopia lentis (downward displacement) is seen in homocystinuria. Upward displacement is seen inMarfan syndrome. There are no changes in the lens in phenylketonuria or multiple carboxylasedeficiency10) An infant presents with multiple congenital hemangomas in an generalized distribution. What isthe most serious associated condition?A. None of the answers are correctB. All of the answers are correctC. Obstructive jaundiceD. Congestive Heart FailureCorrect ChoiceE. Portal hypertensionHigh output congestive heart failure can lead to death in these children. Obstructive jaundice andportal hypertension both occur, but are less likely to cause death. The hemangiomas will undergospontaneous regression.11) What medication may exacerbate this autosomally dominant, acnatholytic disorder?A. LithiumCorrect ChoiceB. Oral contraceptivesC. Phenytoin 3
  4. 4. D. CorticosteroidsE. Anti-malarialsDariers disease is autosomal dominant condition characterized by hyperkeratotic papules coalescinginto warty plaques and cobblestoned papules on mucosal surfaces. The cutaneous manifestationsmay be exacerbated by lithium.12) Which of the following subtypes of Ehlers-Danlos Syndrome (EDS) is associated with earlydemise?A. Type 4 (Vascular) Correct ChoiceB. Type 5 (X-linked)C. Type 1 (Gravis)D. Type 7 (Arthrochalasis multiplex congenita)E. Type 10 (Fibronectin)Ehlers-Danlos Syndrome type 4 (Vascular) is caused by mutations in collagen 3 in some cases.There is a tendency to develop arterial and visceral rupture resulting in early death.13) An infant presents with poikiloderma on his face, buttocks, arms and legs. He is also noted tohave a hypoplastic thumb and no radius. Yearly ophthalmologic examination is indicated because ofthe infant is at risk for developing:A. Subcapsular lens displacementB. Macular degenerationC. GlaucomaD. Copper depositionE. CataractsCorrect ChoiceThe patient described has Rothmund-Thomson syndrome (or poikiloderma congentiale), anautosomal recessive disease localized to chromosome 8 and believed to be due to a DNA helicasemutation (RECQL4). 40-50% of patients will develop juvenile cataracts before puberty. Other clinicalfeatures include alopecia, dystrophic nails, short stature, hypogonadism and dental dysplasia.14) Retention of primary teeth a dental finding of which of the following conditions?A. Letterer-Siwe diseaseB. Tuberous sclerosisC. Hypomelanosis of ItoD. Hyper-IgE syndrome Correct ChoiceE. Jackson Sertoli syndromeHyper-Immunoglobulin E syndrome is an autosomal dominant condition with impaired regulation ofIgE function and deficient neutrophil chemotaxis. There is increased susceptibilty to infections andincreased IgE serum levels. Retained primary teeth and lack of development of secondary teeth arecharacteristic findings. The remaining conditions do not have this as a prominent finding.15) A patient with a white, spongy overgrowth of the buccal mucosa that has passed in anautosomal dominant fashion is most likely related to a mutation in which of the following? 4
  5. 5. A. Keratin 6b/17B. Keratin 1/10C. Keratin 6a/16D. None of these options are correctE. Keratin 4/13Correct ChoiceThis description is most likely a white sponge nevus, an autosomal dominant defect in keratin 4/13.Keratin 1/10 is mutated in epidermolytic hyperkeratosis and Unna-Thost PPK, Keratin 6a/16 inpachyonychia congenita type I, and keratin 6b/17 in pachyonychia congenita type II.16) Dental enamel pits are seen in which of the following conditions?A. Hypomelanosis of ItoB. Tuberous sclerosisCorrect ChoiceC. Hyper-IgE syndromeD. Letterer-Siwe diseaseE. Jackson Sertoli syndromeTuberous sclerosis is an autosomal dominant condition caused by mutations of the TSC1 (hamartin)or TSC2 (tuberin) genes. These are tumor suppressor genes. Skin findings include hypopigmentedmacules, connective tissue nevus, facial angiofibromas, periungual fibromas and cafe au laitmacules. Dental enamel pits and gingival fibromas are oral findings that are associated with thiscondition. The remaining conditions do not have dental pits.17) A 4-year old boy presents with generalized white scale. The mother reports that her son wasborn with a tight membrane enveloping his body. Peripheral blood smear is within normal limits.What is the most likely diagnosis?A. ichthyosis vulgarisB. lamellar ichthyosisC. neutral lipid storage diseaseD. netherton syndromeE. Congenital ichthyosiform erythrodermaCorrect ChoiceThe most likely diagnosis is Congenital ichthyosiform erythroderma. In neutral lipid storage disease,the peropheral blood smear would demonstrate lipid vacuoles in leukocytes and monocytes.Lamellar ichthyosis is characterized by plate-like scale in children/adults. Netherton syndrome ischaracterized by ichthyosis linearis circumflexa. Ichthyosis vulgaris does not typically present withcollodian baby18) Mosaic mutations in PTEN are seen in which of the following conditions?A. Gardner syndromeB. Noonan syndromeC. Incontinentia pigmentiD. Proteus syndrome Correct ChoiceE. Beckwith-Wiederman syndrome 5
  6. 6. Proteus syndrome is a sporadic condition caused by postzygotic mosaic mutations in PTEN. Clinicalfeatures include subcutaneous lymphovenous malformations, capillary malformations, lipomas,connective tissue nevi of palms/soles, hemihypertrophy, frontal bossing, hyperostoses of epiphyses& skull (especially external auditory canal), scoliosis, bilateral ovarian cystadenomas, and parotidmonomorphic adenomas.19) Which syndrome is characterized by hyperhidrosis, lack of pain sensation, hypersalivation, andabsent fungiform papillae?A. Rubinstein-Taybi syndromeB. Noonan SyndromeC. Turner SyndromeD. Riley-Day Correct ChoiceE. Cornelia de lange SyndromeRiley-Day syndrome is also known as Familial Dysautonomia. It is an autosomal recessive disorderwith the gene defect on the long arm of chromosome 9. Patients have unmyelinated sensory andsympathetic neurons and autonomic dysfunction, leading to hyperhidrosis, decreased cornealsensation and tear flow, hypersalivation, gastroesophageal reflux, decreased deep tendon reflexes,and lack of pain sensation. They also exhibit abnormal histamine skin test.20) Homocystinuria is caused by a defect in:A. holocarboxylase synthetaseB. biotinidaseC. phenylalanine hydroxylaseD. cystathione beta-synthetaseCorrect ChoiceE. gp91-phoxCystathione beta-synthetase is defective in homocystinuria, an autosomal recessive conditionscharacterized by increased homocystine and methionine levels in blood and urine. Other findingsinclude a malar flush, DVTs/emboli, cardiovascular disease, livedo reticularis, leg ulcers, blondehair/fiar complexion, downward lens dislocation, glaucoma, mental retardation, seizures, psychiatricdisorders and a marfanoid body habitus. The other enzymes are not involved in this condition.21)Hypoplasia of the breast can be seen in whichdisease? A. anhidrotic ectodermal dysplasiaCorrect Choice B. osteogenesis imperfecta C. congenital syphilis D. Marfan syndrome E. Maffucci syndromeAnhidrotic ectodermal dysplasia is a X-linkedrecessive disease caused by mutations inectodysplasin, a member of the tumor necrosisfamily. Patients may have dry skin with pigmentationperiorbitally, hypohidrosis, sparse hair, hypo-anodontia, nail dystrophy, and frontal bossing, and 6
  7. 7. saddle nose deformity. In addition to abnormalities ofother ectodermally derived structures, the breast andnipple-areolar complex may be absent or hypoplastic.22) Which radiologic finding is associated in Fanconis anemia?A. posterior iliac hornsB. absent radiiCorrect ChoiceC. osteopoikilosisD. absent thumbE. osteopathia striataFanconis anemia is an inherited disease that primarily affects the bone marrow, resulting inpancytopenia. It is also associated with a broad variety of physical anomalies. Cutaneous findingsinclude cafe-au-lait macules and vitiligo.23) Birt-Hogg-Dube syndrome is most strongly associated with which of the following malignancies?A. Renal cell carcinoma Correct ChoiceB. Eccrine syringofibroadenomaC. Trichoepithelial carcinomaD. MedulloblastomaE. Basal cell carcinomaBirt-Hogg-Dube syndrome is characterized by multiple fibrofolliculomas, trichodiscomas, acro-collagenomas, lipomas, and oral fibromas. Patients develop renal cell carcinoma, colon cancer, andmedullary thyroid carcinoma.24) A seven month old infant diagnosed with eczema on her face returns for a diaper-rash follow-up. A one-month trial of topical antifungals has failed to improve the infant’s systems. The part ofthe physical exam that might prove most useful include:A. Hearing testB. Palpation of abdomenC. Examination of palms and solesCorrect ChoiceD. Stool samples 7
  8. 8. E. Fontanelle examinationAcrodermatitis enteropathica presents itself in infancy once breastfeeding has stopped. It canclinically mimic atopic dermatitis, seborrheic dermatitis and candidiasis. Clinical features includescaly red rash around mouth, eyes, and palms, diarrhea, stomatitis, glossitis, alopecia, and failureto thrive.25) What is the inheritance pattern of chronic granulomatous disease?A. Autosomal dominantB. SporadicC. X-linked recessiveCorrect ChoiceD. X-linked dominantE. Autosomal recessiveChronic granulomatous disease is inherited in an x-linked recessive manner. There are mutationspresent in CYBA (a cytochrome subunit), CYBB, and NCF1 & 2 (neutrophil cytosol factors 1 & 2).26) Epidermolysis bullosa simplex is caused by blistering in which structure?A. Spinous layer keratinocyteB. Granular layer keratinocyteC. Basal layer keratinocyte Correct ChoiceD. Sublamina densaE. Lamina densaEpidermolysis bullosa simplex is caused by mutations in keratin 5 and 14 resulting in bullae withinbasal cell keratinocytes.27) Hyperextesible skin, gaping wounds, cigarette-paper scars, molluscoid pseudotumors, andcalcified subcutaneous nodules are characteristic of which syndrome?A. Marfan syndromeB. Congenital contractural arachnodactylyC. Ehlers-Danlos Syndrome Correct ChoiceD. Cutis laxaE. Pseudoxanthoma elasticumThe most common type of EDS is EDS type I (gravis). Cutaneous features include hyperextensibleskin, gaping wounds, cigarette-paper scars, molluscoid pseudotumors, calcified subcutaneousnodules, and bruises. Systemic features include hypermobile joints with dislocation, hernias, mitralvalve prolapse, blue sclerae, Gorlin’s sign (tongue reaches nose), and absence of the lingualfrenulum28) Lamellar ichthyosis is caused by mutations in which of the following genes?A. Phytanoyl coenzyme A hydroxylase deficiencyB. Arylsulfatase EC. Steroid sulfatase 8
  9. 9. D. Transglutaminase Correct ChoiceE. Fatty aldehyde oxidoreductaseNonbullous congenital ichthyosiform erythroderma and lamellar ichthyosis are caused by mutationsin the transglutaminase gene.29) The coast of Maine cafe au lait macule is a common finding in which of the followingsyndromes?A. Russell-Silver syndromeB. McCune-Albright syndromeCorrect ChoiceC. Watson syndromeD. Tuberous SclerosisE. Neurofibromatosis type IMcCune-Albright syndrome is due to a sporadic somatic mutation in Gs subunit of adenylate cyclase.The "coast of Maine" cafe au lait macule is a characteristic finding. Other findings in cludepolyostotic fibrous dysplasia and precocious puberty. Tuberous sclerosis, Neurofibromatosis type I,Watson syndrome (pulmonic stenosis and CALMs) and Russell-Silver syndrome (CALMs, shortstature, precocious puberty, cryptorchidism and musculoskeletal/craniofacial defects) all haveCALMs as a feature, but not the jagged type seen in McCune-Albright syndrome.30) Enchondromas and chondrosarcomas are most strongly associated with which of the followingsyndromes?A. Nonne-Milroy diseaseB. Blue rubber bleb nevus syndromeC. Maffucci syndrome Correct ChoiceD. Osler-Weber-Rendu syndromeE. Proteus syndromeMaffucci syndrome is a sporadic condition caused by defects in the parathyroid hormone/parathyroidhormone related protein type 1 receptor. There are venous malformations of distal extremities, andbenign enchondromas that can degenerate into chondrosarcomas.31) Epistaxis in early childhood to teens followed by multiple cutaneous and gastrointestinaltelangectasias describes which of the following syndromes?A. CREST syndromeB. Maffucci syndromeC. Hereditary Hemorrhagic Telangiectasia syndromeCorrect ChoiceD. Ataxia telangectasiaE. Fabry diseaseHereditary Hemorrhagic Telangiectasia syndrome is described above. The first signs in over 50% ofcases is epistaxis in childhood to young adulthood. Telangectiasias develop in the 30s and 40s.Other findings include gastrointestinal telangiectasia, hepatic and pulmonary arteriovenousmalformations. The other syndromes listed can have cutaneous vascular lesions and should beconsidered on the differential for hereditary hemorrhagic telangiectasia syndrome 9
  10. 10. 32) Which syndrome is characterized by broad thumbs, a large beaked nose, and capillarymalformation?A. Rubinstein-TaybiCorrect ChoiceB. Bloom syndromeC. Proteus syndromeD. Ehlers-Danlos syndromeE. KlinefelterRubinstein-Taybi syndrome has been associated with a deletion localized to the short arm ofchromosome 16. Patients are severely retarded with strabismus, crytorchidism, and congenitalheart defects. They have a characteristic beaked nose with nasal septum below alae accompaniedby a broad nasal bridge, downslanting palpebral fissures, and broad thumbs and halluces.33) Which of the following immunoglobulins is commonly decreased in Wiskott-Aldrich syndrome?A. IgEB. IgGC. IgAD. IgMCorrect ChoiceE. IgDIgM is decreased in WAS. IgA, IgD and IgE levels are all elevated. IgG is not abnormal in WAS.34) Mutations affecting the VEGF receptor-3 cause which of the following disorders?A. Lymphedema-distichiasis syndromeB. Noonan syndromeC. Lymphedema and ptosisD. Hereditary hemorrhagic telangiectasiasE. Hereditary lymphedema (Nonne-Milroy disease) Correct ChoiceHereditary lymphedema (Nonne-Milroy disease) is an autosomal dominant condition caused bymutations in the FLT4 gene which encodes for VEGF receptor-3. There is congenital lymphedemaand chylous ascites, scrotal swelling, intestinal tract protein loss, persistent bilateral pleuraleffusion, and hypoproteinemia35) What is a possible gene defect in this patient with a white forelock?A. tyrosinaseB. c-kitCorrect ChoiceC. P geneD. tyrosinase-related protein 1E. PAX3Piebaldism is an autosomal dominant condition caused by a mutation in c-kit which is a mast andstem cell growth factor. This mutation leads to defective melanoblast proliferation and depigmentedpathces on the trunk and white forelock. Other features include Hirschprung disease, mentalretardation, deafness and cerebellar ataxia. 10
  11. 11. 36) Beare-Stevenson cutis gyrata syndrome is linked with mutations in:A. ATP7AB. BSCL2C. None of these answers are correctD. Fibroblast growth factor receptor 2Correct ChoiceE. LMNABeare-Stevenson cutis gyrata syndrome has been linked to mutations in fibroblast growth factorreceptor 2. This syndrome is characterized by: craniosynostosis, ciutis gyrata, acanthosis nigricans,anogenital anomalies, skin tags, prominent umbilical stump, furrowed palms and soles. Apertsyndrome is also linked to this mutation. BSCL2 is linked to Berardinelli-Seip congenitallipodystrophy, LMNA to Familial partial lipodystrophy and ATP7A to Menkes kinky hair syndrome.37) Which of the following medications is a teratogen associated with a aplasia cutis congenita?A. Methimazole Correct ChoiceB. AlcoholC. LithiumD. WarfarinE. PropranololAplasia cutis congenita is characterized by well-demarcated erosions at birth that heal with atrophic,alopecic scars. Some cases are caused by medications, with methimazole considered a teratogenparticularly associated with this condition.38) A patient with Cowden syndrome presents with a history of breast carcinoma. What othercarcinoma should she be examined/screened for?A. UterineB. ThyroidCorrect ChoiceC. OvarianD. BoneE. ColonPatients with Cowden syndrome are at increase risk for thyroid and breast adenocarcinomas.Ovarian, uterine, colon and bone cancer risks are not elevated in this syndrome.39) Which ocular finding may be seen in a patient with this skin condition?A. comma-shaped corneal opacitiesB. congenital hypertrophy of the retinal pigmented epitheliumC. retinitis pigmentosaD. angioid streaksCorrect ChoiceE. pingueculae 11
  12. 12. Pseudoxanthoma elasticum is caused by a defect in connective tissue. Angioid streaks develop whena rupture occurs in Bruch;s membrane.40) Which of the following elastic tissue diseases demonstrates calcified elastic fibers?A. Pseudoxanthoma elasticumCorrect ChoiceB. Cutis laxaC. Buschke-ollendorf syndromeD. Marfan syndromeE. AnetodermaPseudoxanthoma elasticum is usually an autosomally recessive inherited condition due to adefective transport protein, ABCC6. The clinical manifestations of the disease arise from fragmentedand calcified fibers of the skin, eyes and arteries. Patients may have yellow papules, looseredundant skin, angioid streaks and hemorrhage. Histologically, the hallmark of pseudoxanthomaelasticum is calcified elastic fibers.41) Junctional epidermolysis bullosa with pyloric atresia is associated with mutations in:A. Laminin 5B. The alpha-6 subunit of integrinC. The beta-4 subunit of integrinD. PlectinE. Both subunits of integrin can have mutations causing this type of junctional epidermolysisbullosaCorrect ChoiceBoth subunits of integrin can have mutations causing this type of junctional epidermolysis bullosa.Plectin is associated with epidermolysis bullosa simplex with muscular dystrophy. Laminin 5 ismutated in Herlitz and non-Herlitz types of junctional epidermolysis bullosa.42) Which of the following condition is NOT found in Von-Hippel Lindau syndrome?A. PheochromocytomaB. Bilateral retinal hemangioblastomasC. Renal cell carcinomaD. Connective tissue neviCorrect ChoiceE. Cerebellar/CNS hemangioblastomasVon Hippel-Lindau syndrome is characterized by all the options listed except connective tissue nevi.Other findings include pancreatic cysts/carcinoma and cutaneous capillary malformations of thehead and neck and polycythemia.43) Which syndrome is due to a defective secreted mammilian Ly6/uPAR-related protein-1?A. Nethertons syndromeB. Mal de Meleda syndromeCorrect ChoiceC. Refsums syndromeD. Haim-Munk syndrome 12
  13. 13. E. Sjogren-Larsson syndromeMal de Meleda, also known as keratoderma palmoplantaris transgrediens, is due to a defect insecreted mammilian Ly6/uPAR-related protein or SLURP-1.44) You are examining a child with mild albinism, immunodeficiency and silver grey highlights in hishair. You diagnose the child with Chediak-Higashi syndrome. Why are you confident that this isn’tGriscelli syndrome?A. Griscelli syndrome has no changes in hair colorB. None of these answers are correctC. All of these answers are correctD. Griscelli syndrome does not have albinism as a featureE. Giant lysosomal granules are present in neutrophils in the blood smearCorrect ChoiceChediak-Higashi syndrome and Griscelli syndrome have similar features including silver-greyhighlights of hair, immunodeficiency, mild albinism and an accelerated phase of disease. Examininga peripheral blood smear is helpful in distinguishing between these two syndromes. Patients withthe LYST defect (a lysosomal storage transport gene) have Chediak-Higashi syndrome and will havegiant lysosomal granules visible in white blood cells on a blood smear45) Adenosine deaminase deficiency is seen in which immunodeficient disease?A. Wiskott-Aldrich syndromeB. Chronic granulomatous diseaseC. Leiner’s diseaseD. Job syndromeE. Severe combined immunodeficiency syndromeCorrect ChoiceSevere combined immunodeficiency is a heterogeneous group of disorders characterized bydecreased humoral and cell mediated immunity. Patients may have recurrent infections includingcutaneous ones, GVHD (due to in utero cmaternal lymphocytes), sepsis, oral candidiasis, anddiarrhea. Implicated genes include the IL-2 receptor (x-linked recessive form) and adenosinedeaminase deficiency (autosomal recessive form).46) Dystrophic epidermolysis bullosa is associated with mutations in collagen VII. Trauma or frictioninduced blistering in these patients have a plane a splitting in the:A. Stratum spinosumB. None of these answers are correctC. Sublamina densaCorrect ChoiceD. Stratum basaleE. Lamina lucidaThe split in dystrophic epidermolysis bullosa is found in the sublamina densa, where the collagen VIIanchors the epidermis to the anchoring plaques in the dermis. The remaining options are incorrect47) What is the most likely nail findings in a patient who has this autosomal dominant disease withthese keratotic papules and cobblestoning of the oral mucosa? 13
  14. 14. A. Red and white longitudinal bandsCorrect ChoiceB. KoilonychiaC. Pincer nailsD. MelanonychiaE. Half and half nailsDariers disease is an autosomal dominant disorder characterized by greasy hyperkeratotic papules.The papules often coalesce into a warty plaque and have a tendency for secondary viral or bacterialinfection. The mutation is in calcium ATPase 2A2. The classic nail finding is red and whitelongitudinal bands with V-shaped nicking.48) Low-cystine content in hair and nails may contribute to the phenotype seen in:A. Wilson’s diseaseB. BjornstadC. Tay SyndromeCorrect ChoiceD. Menke’s Kinky Hair syndromeE. NethertonsTay Syndrome is also known as trichothiodystrophy, or (P)IBIDS: (photosensitivity), icthyosis,brittle hair, intellectual impairment, decreased fertility, and short stature. Hair shaft has acharacteristic “tiger tail” appearance under polarized light and the low cystine content in hair andmails is thought to be responsible for the phenotype seen.49) Bilateral ovarian cystadenomas and parotid monomorphic adenomas are seen in which of thefollowing conditions?A. Beckwith-Wiederman syndromeB. Von-Hippel-Lindau syndromeC. Proteus syndrome Correct ChoiceD. Cowden syndromeE. Noonan syndromeProteus syndrome is a sporadic condition caused by postzygotic mosaic mutations in PTEN. Clinicalfeatures include subcutaneous lymphovenous malformations, capillary malformations, lipomas,connective tissue nevi of palms/soles, hemihypertrophy, frontal bossing, hyperostoses of epiphysesand skull (esp. external auditory canal), scoliosis, bilateral ovarian cystadenomas, and parotidmonomorphic adenomas.50) Maffucci syndrome is has characteristic venous malformations of the distal extremities andbenign endochondromas which can compromise bone strength and lead to chondrosarcomas. Thedefect causing this believed to be the PTH/PTHrP type I receptor which is inherited in whichmanner?A. Autosomal recessiveB. X-linked recessiveC. X-linked dominantD. Autosomal dominant 14
  15. 15. E. SporadicCorrect ChoiceMaffucci syndrome is inherited in a sporadic manner51) What phenotype results from a low activity of double stranded RNA adenosine deaminase?A. oculocutaneous albinism type 4B. PiebaldismC. Waardenbergs syndrome type 2D. Tietz syndromeE. dyschromatosis symmetrica hereditariaCorrect ChoiceDyschromatosis symmetrica hereditaria (or acropigmentation symmetrica of Dohi) is an autosomaldominant disease with hypo and hyper pigmented macules and patches on the dorsal hands andfeet associated with a low activity of double stranded RNA adenosine deaminase52) Which of the following is not classically associated with pheochromoctyoma?A. Multiple Endocrine Neoplasia Type IIAB. NeurofibromatosisC. Multiple Endocrine Neoplasia Type IIBD. Cobb SyndromeCorrect ChoiceE. Von-Hippel-Lindau SyndromeCobb syndrome is a sporadic disease characterized by cutaneous vascular malformations associatedwith malformations of the spinal cod.53) A 17 y/o man presents with facial acne that he would like treated. You notice that he has finebrown scale on his neck and do a complete skin exam. This scale is present on the remainder of hisbody, sparing his palms, soles and flexural areas. He informs you that his uncles on his mother’sside have similar skin findings. He is not concerned about the skin and would like to proceed withacne treatment only. What other clinical exam should you perform to screen for a potentialmalignancy to which this patient is at higher risk for acquiring?A. LungB. RectalC. AbdominalD. TesticularCorrect ChoiceE. Lymph nodeMen with x-linked ichthyosis are at increased risk of testicular cancer and cryptorchidism. Atesticular exam is simple to perform and a good screening exam for detecting testicularabnormalities. The remaining exams are not useful as these patients are not at higher risk for othertypes of cancer54) Naxos syndrome is characterized by a right sided cardiomyopathy, wooly hair, andkeratoderma. The epidermal structure defective in Naxos syndrome is:A. desmoplakinB. plakoglobinCorrect Choice 15
  16. 16. C. desmoglein 3D. desmoglein 1E. Keratin 1/10Plakoglobin is an intracellular desmosomal component which binds desmogleins/desmocollins on oneside and to desmoplakin on the other. Desmoplakin in turn binds to the keratin intermediatefilaments, K1/10 in most cases. Mutation of desmoplakin leads to CarvajaL syndrome, which isassociated with a striate palmoplantar keratoderma, woolly hair and Left sided cardiomyopathy. Asimple way to remember this is the L in Carvajal cooresponds to the Left sided cardiomyopathy vs.the right sided disease in Naxos disease.55) What cutaneous manifestation is associated with familial cerebral cavernomas?A. hyperkeratotic cutaneous capillary-venous malformations(HCCVM)Correct ChoiceB. Verrucous hemangiomsC. segmental facial hemangiomasD. Tufted angiomasE. Glomeruloid hemangiomasFamilial cerebral cavernomas are due to a defect in the CCM gene which encodes the KRIT-1protein. These patients often times have hyperkeratotic cutaneous capillary-venous malformations.56) "Mousy" odor of urine is characteristic of which of the following syndromes?A. Maple Syrup Urine diseaseB. Hunter diseaseC. AlkaptonuriaD. Hurler diseaseE. PhenylketonuriaCorrect ChoicePhenylketonuria will cause a "mousy" odor in the urine. Patients with Alkaptonuria will have blackurine. Maple syrup urine disease will have a sweet odor. Hunter/Hurler diseases are not associatedwith urinary issues.57) Which disease can clinically mimic pellagra but is inherited in an autosomal recessive fashionand is due to a defect in the transport of neutral amino acids?A. FabryB. WilsonsC. Gaucher’sD. Hartnup DiseaseCorrect ChoiceE. HemochromatosisThe clinical manifestation of Hartnup disease is similar to that of pellagra because the resultantdefect in the transport of amino acids leads to low levels of tryptophan. Since tryptophan is requiredto make nicotinic acid, pts with Hartnup disease manifest the same symptoms as niacin-deficientpatients (pellagra). 16
  17. 17. 58) A child presents with the hair finding seen in the image in addition to brittle nails, keratosispilaris, abnormal teeth and cataracts. Which of the following abnormalities is the most likelymutated?A. Keratin hHb1/hHb6Correct ChoiceB. Keratin 1/10C. Keratin 2eD. Keratin 6/17E. Keratin 6/16Keratin hHb1/hHb6 is defective in monilethrix, which is described above. Keratin 1/10 defects arefound in epidermolytic hyperkeratosis, K6/16 in inflamed skin and pachyonychia congenita type I,K6/17 in pachyonychia congenita type II and K2e in Ichythosis bullosa of Siemens59) Which malignancy is associated with Cowden syndrome?A. Colon cancerCorrect ChoiceB. Renal cancerC. Lung cancerD. Basal cell cancerE. Ovarian cancerCowden syndrome is a autosomal dominant syndome with tricholemmomas, oral mucosal papules,acral keratotic papules, thyroid goiter, GI polyps, and fibrocystic breast disease. Malignantassociations include breast, thyroid follicular carcinoma, and colon adenocarcinoma.60) The combination of gastrointestinal polyposis, nail atrophy, alopecia, generalized pigmentationof skin, and melanotic macules of the fingers is characteristic of which of the following syndromes?A. Cronkhite-Canada syndrome Correct ChoiceB. Bannayan-Riley-Ruvalcaba syndromeC. Cowden syndromeD. Nicolau-Balus syndromeE. Peutz-Jeghers syndromeCronkhite-Canada syndrome is a sporadic gastrointestinal polyposis syndrome associated with nailatrophy, alopecia, generalized pigmentation of the skin, and melanotic macules on the fingers.61) Which of the following syndromes is associated with cutis marmorata?A. Netherton’sB. Cornelia de Lange syndromeCorrect ChoiceC. Hemansky-Pudlak syndromeD. Maffucci syndromeE. Papillon-Lefevre syndromeCornelia de Lange is also known as Brachmann-de Lange syndrome. Cutaneous manifestationsinclude cutis marmorata, hirsutism, hypoplastic nipples and umbilicus. Patients also have small 17
  18. 18. hands and feet. They have characteristic facies which include hirsutism on the forehead,trichomegaly, synophrys, anteverted nostrils, long philtrum, and low-set ears.62) Lamellar ichthyosis is caused by a defect in transglutaminase 1. It can present as a colloidionbaby at birth with subsequent large thick plates of scale especially on flexures, ectropion andeclabium. If two unaffected carrier parents have a child, how likely is their child to have thiscondition?A. Only male offspring are affectedB. None of these answers are correctC. Only female offspring are affectedD. 25%Correct ChoiceE. 75%Lamellar ichthyosis is an autosomal recessive condition. If each parent is a heterozygous carrier,there is a 25% chance that the child will be affected, 50% chance that the child will be aheterozygous carrier and a 25% chance that the child will not be a carrier or affected with lamellarichthyosis.63) A 18 yo man presents for evaluation of foot lesions. There are thick hyperkeratotic plaquessymmetrically on only the weight bearing plantar surfaces. What test(s) should this patient bereferred for?A. Thoracic CTB. Head CTC. EndoscopyCorrect ChoiceD. Hepatic ultrasoundE. Knee filmsThe patient likley has Howel-Evans Syndrome. These patients present with symmetric focal weightbearing PPK in the second decade to adulthood. After the third decade, esophageal carcinoma canoccur. These patients should have periodic endoscopic evaluation.64) To help diagnose trichothiodystrophy, which of the following levels are decreased in hairs ofaffected individuals?A. HistidineB. ArginineC. CysteineCorrect ChoiceD. GlycineE. PhenylalanineCysteine and Methionine levels are decreased in hair and nails of patients with trichothiodystrophy.Other sulfur containing amino acids include: Gluthathione, Taurine, and Homocysteine. Testing hairsfor decreased sulfur content is an indirect method of determining this. The other listed amino acidsare present in normal levels in the hair and nails of trichothiodystrophy patients65) Adenosine deaminase deficiency is associated with which of the following disorders?A. Xeroderma pigmentosum 18
  19. 19. B. Wiskott Aldrich syndromeC. GoutD. Severe combined immunodeficiencyCorrect ChoiceE. Job syndromeAdenosine deaminase deficiency is associated with severe combined immunodeficiency. The mostcommon inheritance is x-linked recessive. It is a mixed group of disorders all sharing defects in cell-mediated and humoral immunity. Skin findings include: candidal infections, mucocutaneous,bacterial pyodermas, seborrheic-like dermatitis/lichen planus-like sclerodermatous changes, aplasticthymus and pneumonias. The other listed syndromes are not associated with adenosine deaminasedeficiency.66) Which eye findings would be expected in an individual with this disorder associated withatherosclerosis?A. dendritic corneal ulcerationsB. salt and pepper retinitis pigmentosaC. angoid streaksCorrect ChoiceD. keratoconusE. ectopia lentisPseudoxanthoma elasticum is an autosomal rescessive or autosomal domminant disease caused bya mutation in ABCC6 (adenosine triphosphate-binding cassette subfamily C member 6). Associatedfindings include gastric artery hemorrhage, angiod streaks, retinal hemorrhage, atheroscleroticdisease, and a possible increased risk of first trimester miscarriage.67) Which of the following is caused by a mutation in a gene which codes for steroid sulfatase?A. Lamellar icthyosisB. Chediak-HigashiC. X-linked ichthyosisCorrect ChoiceD. Lesch-nyhan diseaseE. Fabry diseaseThe mutation in X-linked icthyosis is found in the gene for aryl sulfatase C, a steroid sulfatase. Thegenetic defect in Fabry disease occurs in alpha-galactosidase A (which hydrolyzes glycolipids andglycoproteins), the defect in lamellar icthyosis codes for transglutaminase 1 and the defect inchediak higashi occurs in a lysosomal transport protein.68) Meleda is an island off the coast of Croatia. Its inhabitants have an increased frequency of amalodorous transgradiens palmoplantar keratoderma in a stocking-glove distribution. This conditionis autosomal recessive with a defect in:A. Cathepsin CB. Keratin 1/9C. SLURP1 geneCorrect ChoiceD. TOC geneE. Loricrin 19
  20. 20. SLURP1 (Secreted LY6/UPAR-related protein 1) is defective in Mal de Meleda. Keratin 1/9 aredefective in Unna-Vorner/Thost palmoplantar keratoderma, an AD diffuse symmetric non-transgradiens PPK. TOC gene is defective in Howel-Evans syndrome, an AD PPK associated withfocal, pressure-related, non-transgradiens PPK and esophageal cancer/oral leukoplakia. Loricrinmutations are seen in Vohwinkel syndrome variant and symmetric progressive erythrokeratodermia.Cathepsin C defects are seen in Haim-Munk syndrome(PPK+periodontitis+acroosteolysis+onychogryphosis) and Papillon-Lefevre syndrome (sharplydemarcated transgradiens, stocking-glove PPK+periodontitis+dural calcifications and choroidsattachments)69) A patient with thyroid carcinoma and cobblestone-like changes of the oral mucosa will alsolikely have:A. SyringomasB. CylindromasC. TrichoepitheliomasD. FibrofolliculomasE. TricholemmomasCorrect ChoiceThe patient described may have Cowdens syndrome, an autosomal dominant condition caused by adefect in the PTEN tumor suppressor gene. Patients with Cowdens disease are at increased risk forthyroid and breast carcinoma. In addition, they characteristically have multiple hamartomatouspolyps of the gastrointestinal tract that are typically benign. Cutaneous features of Cowdenssyndrome which may serve as clues to the diagnosis include multiple oral papillomas with a"cobblestone" appearance on the lips, gingival, and buccal mucosa, acral keratotic papules on thedorsal hands and wrists, palmoplantar punctate keratoses and multiple facial tricholemmomas.Patients with this condition need careful malignancy surveillance.70) What is the inheritance pattern of dermatosis with acantholysis?A. autosomal recessiveB. X-linked recessiveC. X-linked dominantD. autosomal dominantCorrect ChoiceE. sporadicHailey-Hailey, or Familial Benign Pemphigus, is an autosomal dominant genodermatosis which iscaused by a mutation in ATP2C1. Vesicles and erythematous plaques develop in the skin folds suchas axillae and groin area.71) A patient with myotonic dystrophy and multiple skin lesions characterized by the pathologyimage shown most likely has activating mutations in which of the following?A. desmogleinB. desmoplakinC. plakoglobinD. beta-cateninCorrect ChoiceE. alpha 6-beta 4 integrinMyotonic dystrophy with multiple pilomatricomas is described above. Activating mutations in Beta-catenin are found in this syndrome. The other listed options are desmosomal proteins and are notinvolved in this syndrome. 20
  21. 21. 72) Painful crises and whorled corneal opacities are seen with which of the following enzymeabnormalities?A. alpha-galactosidase ACorrect ChoiceB. glucocerebrosidaseC. iduronate sulfataseD. glucoronidaseE. homogentisic acid oxidasePainful crises and whorled corneal opacities are found in Fabry disease which is caused by a defectin alpha-galactosidase A. The remaining conditions do not have these findings73) A patient with melanoma and a malignant glioma is diagnosed with Li-Fraumeni syndrome.Which of the following tumors occurs most frequently in this disease?A. Breast carcinomaB. Lung carcinomaC. RhabdomyosarcomaCorrect ChoiceD. LeukemiaE. Adrenocortical carcinomaLi-Fraumeni syndrome is a familial tumor syndrome caused by mutations in the tumor suppressorgene p53. They are at risk for a wide range of malignancies with particularly high occurrences ofsoft tissue sarcomas, breast caner, brain tumors, acute leukemia, and adrenal cortical carcinoma.Soft tissue sarcomas are among the most common reported with this disease.74) Most common malignancy to develop in a patient with tricholemmomas, acral verrucouspapules and cobble-stoning of buccal and gingival mucosa?A. Colon cancerB. Breast cancerC. MelanomaD. LymphomaE. Thyroid cancerCorrect ChoiceCowdens syndrome is an autosomally dominant inherited defect of PTEN. Patient may present withmultiple trichilemmoma, hamartomatous tumors of the breast, thyroid and endometrium, acralkeratoses and papillomatous papules. Thyroid carcinoma is the most common form malignancy toarise in these patients75) You are consulted on a patient with possible Nethertons Syndrome. Which location of the bodywould most likely have hairs demonstrating trichorrhexis invaginata?A. none of these answers are correctB. scalpC. eyebrowCorrect ChoiceD. all of these answers are correct 21
  22. 22. E. eyelashEyebrow hair is most common site with hairs demonstrating trichorrhexis invaginata.76) Beckwith-Wiederman syndrome is characterized by which of the following triads?A. Epistaxis, telangictases, and gastrointestinal tract bleedingB. Omphalocele, venous malformations, and ataxiaC. Exophthalmos, macroglossia, and gigantism Correct ChoiceD. Hemangioblastomas, renal cysts and renal cell carcinomaE. Enlarged limb, port wine stain, and deep venous thrombosisBeckwith-Wiederman syndrome is also known as EMG syndrome as it includes exophthalmos,macroglossia, and gigantism. It is usually a sporadic condition but is sometimes caused byautosomal dominant mutations in p57. Clinical features include facial capillary malformations,macroglossia, visceromegaly with omphalocele, and hemihypertrophy associated with tumors(especially Wilm’s tumors).77) A 16-month old girl presents with patchy alopecia, whorled erythematous scaly eruption, andasymmetric limb shortening. What laboratory or radiologic test may aid in diagnosis?A. Alkaline phosphataseB. Brain MRIC. Bone filmsCorrect ChoiceD. Chest radiographE. Complete blood countThe patient has Conradi-Hunermann Syndrome. This is a X-linked dominant disorder characterizedby ichthyosiform erythroderma in Blaschkos lines in infancy which resolves with follicularatrophoderma, patchy alopecia, short stature, cataracts, scoliosis, assymetric limb shortening. Bonefilms will demonstrate stippled epiphyses. Ichthyosis and stippled epiphyses resolve after infancy.78) A patient presents with multiple flesh colored papules on his face. The pathology report comesback as a fibrofolliculoma. He also has multiple lipomas. Which of the following neoplasms must yoube concerned about?A. Renal Cell CarcinomaB. Colon carcinomaC. All of the options are correctCorrect ChoiceD. Medullary thyroid carcinomaE. None of the options are correctBirt-Hogg-Dube syndrome is described above. Renal cell carcinoma is the most common associationfor internal malignancy, but medullary thyroid and colon carcinomas occur at an increased rate inthese individuals also79) Menke’s kinky hair syndrome is caused by a defect in:A. Gap junction proteinB. Mitochondrial gene 22
  23. 23. C. Copper Transporting ATPaseCorrect ChoiceD. DNA helicaseE. Proto-oncogeneMenke’s kinky hair syndrome is an x-linked recessive disorder caused by a mutation at Xq12 leadingto defective intestinal copper transport80) Retinal hemangioblastomas are found in which syndrome:A. Kasabach-Merritt syndromeB. Klippel-Trenaunay Weber syndromeC. Sturge-Weber syndromeD. Von-Hippel Lindau diseaseCorrect ChoiceE. Osler-Weber-Rendu diseaseVon Hippel-Lindau syndrome is an autosomal dominant condition caused by a defect in the VHLtumor suppressor gene. This disease is characterized by retinal hemangioblastomas, often resultingin visual impairment and blindness if left untreated. In addition, many tumors are seen includingpheochromocytoma, renal cell carcinoma, and hemangioblastomas of the cerebellum, medulla, andspinal cord. Pancreatic and renal cysts are also a feature of this condition. Finally, polycythemia canoccur as a result of erythropoietin production by renal cell carcinoma. Von Hippel-Lindau syndromeis a progressive, universally fatal condition which presents most often in the fourth decade of life81) Mutations in calcium transporters cause which pair of diseases?A. Chondrodysplasia punctata and CHILD syndromeB. Darier’s disease and Hailey-Hailey disease Correct ChoiceC. Lamellar ichthyosis and nonbullous congenital ichthyosiform erythrodermaD. Refsum syndrome and Sjogren-Larsson syndromeE. Erythrokeratodermia variabilis and progressive symmetric erythrokeratodermiaDarier’s disease and Hailey-Hailey disease are caused by mutations in the SERCA calcium ATPase.The former is characterized by hyperkeratotic papules in seborrheic areas, palmar keratoses andpits, red-white longitudinal nail bands, v-shaped distal nail nicks, and cobblestoning of oral andrectal mucosae. The latter is characterized by acantholytic erosions in skin folds82) Which of the following is a potentially serious complication of the blue rubber bleb nevussyndrome?A. Development of lymphedemaB. Gastrointestinal hemorrhage Correct ChoiceC. Development of chondrosarcomasD. Development of lymphedemaE. Development of angiosarcomasBlue rubber bleb nevus syndrome is characterized by multiple tender venous malformations of skinand gastrointestinal tract, which can lead to gastrointestinal bleeding83) A child with phenylketonuria likely presents with which cutaneous problems? 23
  24. 24. A. Alopecia universalisB. Generalized hypopigmentationCorrect ChoiceC. Leg ulcersD. Blue-gray generalized hyperpigmentationE. Generalized hyperpigmentationPhenylketonuria is an autsomal recessive disorder caused by a mutation on the long arm ofchromosome 12. A deficiency of phenylalanine hydroxylase or its cofactor tetrahydrobiopterin leadsto accumulation of phenylalanine. Clinical features include generalized hypopigmentation,eczematous dermatitis, sclerodermoid changes, seizures, psychomotor delay, urine with “mousy”odor, mental retardation84) Patients with Chondrodysplasia punctata can have findings of stippled epiphyses on X-rayexamination. Which other x-linked dominant condition can have stippled epiphyses?A. CHILD syndromeCorrect ChoiceB. Bazex syndromeC. Incontinentia PigmentiD. Goltz syndromeE. Focal Dermal HypoplasiaAll of the syndromes listed have X-linked dominant inheritance. CHILD syndome also has findings ofstippled epiphyses. Incontinentia pigmenti is caused by defecdts in the NEMO gene. Findings includepeg/conical teeth, eye and CNS defects and alopecia. There are no bone abnormalities. FocalDermal Hypoplasia, otherwise known as Goltz syndrome has findings of linear atrophy followingBlaschkos lines with areas of fat herniation, mucocutaneous papillomas and pits, alopecia, naildystrophy, tooth abnormalities and osteopathia striata (striations of the long bones). Bazexsyndrome is associated with follicular atrophoderma, hypohidrosis, hypotrichosis and multiple basalcell carcinomas. There are no bone abnormalities associated85) Comma-shaped corneal opacities are characteristic of which type of ichthyosis?A. X-linked ichthyosis Correct ChoiceB. Nonbullous congenital ichthyosiform erythrodermaC. Lamellar ichthyosisD. Ichthyosis vulgarisE. Refsum syndromeX-linked ichthyosis patients have comma-shaped corneal opacities that are asymptomatic yet highlycharacteristic.86) Painful crises and whorled corneal opacities are seen with which of the following enzymeabnormalities?A. iduronate sulfataseB. glucoronidaseC. glucocerebrosidaseD. alpha-galactosidase ACorrect Choice 24
  25. 25. E. homogentisic acid oxidasePainful crises and whorled corneal opacities are found in Fabry disease which is caused by a defectin alpha-galactosidase A. The remaining conditions do not have these findings.87) In chronic granulomatous disease, the diagnosis is made by which of the following tests?A. Assay for fumarate hydrataseB. Nitroblue tetrazolium reduction assayCorrect ChoiceC. Assay for sphingomyelinaseD. Skin biopsyE. Assay for glucocerebrosidaseChronic granulomatous disease is diagnosed by the nitroblue tetrazolium reduction assay. Theabnormal white blood cells cannot reduce dye due to the inability to produce the respiratory burst.This is needed to kill catalase positive organisms after phagocytosis. Fumarate hydratase isdefective in familial multiple cutaneous leiomyomatosis, sphingomyelinase in Niemann-Pick diseaseand glucocerebrosidase in Gaucher disease88) Milia, atrophoderma vermiculata and eruptive lesions shown in the pathologic image arecharacteristic of which of the following syndromes?A. Banayan-Riley-RuvalcabaB. GorlinC. Nicolau-BalusCorrect ChoiceD. CowdenE. Birt-Hogg-DubeNicolau-Balus syndrome is characterized by eruptive syringomas (shown in the path image), miliaan datrophoderma vermiculata. Cowden syndrome is associated with trichilemmomas, Birt-Hogg-Dube with fibrofolliculoma, and Banayan-Riley-Ruvalcaba is not associated with an adnexalneoplasm89) Which of the following bony defect is found in CHILD syndrome?A. Calcification of falx cerebriB. OsteopoikilosisC. Stippled epiphysesCorrect ChoiceD. Sphenoid wing dysplasiaE. Polyostotic fibrous dysplasiaCHILD syndrome is an X-linked dominant syndrome which is lethal in males. It is caused by aperoxisomal biogenesis disorder. It is characterized by unilateral ichthyosiform erythroderma, limb/visceral hypoplasia, and stippled epiphyses. Stippled epiphyses can also be seen inchondrodysplasia punctata. Polyostotic fibrous dysplasia is found in McCune-Albright syndrome,calcification of falx cerebri in Gorlins syndrome, osteopoikilosis in seen in Buschke-Ollendorfsyndrome90) Epidermolysis bullosa with muscular dystrophy is caused by mutations in which of thefollowing? 25
  26. 26. A. Keratins 5 and 14B. LoricrinC. Collagen 17D. Plectin Correct ChoiceE. Collagen 7Epidermolysis bullosa with muscular dystrophy is caused by mutations in plectin91)Which of the following syndromes is associated withhematologic abnormalities? A. Klippel-Trenaunay-Parks-Weber B. Kasabach-Merritt syndromeCorrect Choice C. Bloom’s syndrome D. Blue rubber bleb nevus syndrome E. Sturge Weber diseaseKasabach-Merritt syndrome is associated withhematologic abnormalities, such asthrombocytopenia, microangiopathic hemolyticanemia, disseminated intravascular coagulation. Thecondition develops from platelet-trapping within alarge hemangioma, most commonly a kaposiformhemangioendothelioma in the retroperitoneallocation.92) Which of the following is caused by a defect in lysosomal transport:A. Chediak-higashiCorrect ChoiceB. oculocutaneous albinism IIC. PiebaldismD. oculocutaneous albinism IE. Bloom’s syndromeChediak higashi is an autosomal recessive disorder caused by a mutation in the LYST gene codes fora lysosomal tracking protein. This protein regulates microtubule mediated lysosomal fusion. A defectin this gene leads to giant lysosomal granules seen in neutrophils (leading to defecting phagocytosisand decreased chemotaxis), melanocytes (pigment dilution), and neurons. OCA1 is tyrosinasenegative albinism; OCA2 is tyrosinase positive albinism with a mutation in P gene on chromosome1593) Which keratins are expressed in the suprabasal palmoplantar epidermis?A. Keratins 4 and 13B. Keratins 8 and 18C. Keratins 1 and 9 Correct ChoiceD. Keratins 5 and 14 26
  27. 27. E. Keratins 1 and 10Keratins are expressed in pairs of acidic and basic keratins and are tissue- and differentiation-specific. Keratins 1 and 9 are expressed in the suprabasal palmoplantar epidermis, keratins 1 and10 in suprabasal nonpalmoplantar epidermis, keratins 2e and 10 in the granular layer, keratins 4and 13 in mucosal epithelium, keratins 5 and 14 in the basal layer, and keratins 8 and 18 in simpleepithelium.94) Dermatofibrosis lenticularis disseminata is seen in which of the following conditions?A. Pseudoxanthoma elasticumB. Focal dermal hypoplasiaC. Ehlers-Danlos syndromeD. Marfan syndromeE. Buschke-Ollendorf syndrome Correct ChoiceBuschke-Ollendorf syndrome is an autosomal dominant disorder characterized by dermatofibrosislenticularis disseminata (cutaneous elastomas distributed symmetrically over the buttocks, trunkand proximal extremities), and osteopoikilosis (round opacities in bones95) A patient with 20 nail dystrophy, steatocystoma multiplex and natal teeth likely has a mutationin the genes coding for:A. Laminin 5B. Plakophilin 1C. Keratins 5 &14D. Keratins 6b & 17Correct ChoiceE. Keratins 6 &16Pachyonychia congenital is an autosomal dominant condition with 20 nail dystrophy. The patientdescribed has Type II (Jackson-Sertole) disease, which includes steatocystoma multiplex, natalteeth, multiple cysts, and micropthalmia, and is caused by mutations in keratins 6b& 17. Type I(Jadassohn-Lewandowsky) also includes focal symmetric PPK, follicular hyperkeratosis, oralleukokeratoses and is caused by mutations in keratins 6 &16. Type III includes the clinical featuresof type I + corneal leukokeratosis. Mutations in keratins 5&14 represents EB simplex, Laminin 5mutation is seen in Junctional EB, and plakophilin 1 mutation is seen in ectodermal dysplasia withskin fragility96) Premalignant leukoplakia of the oral mucosa is associated with:A. Werner SyndromeB. Bloom syndromeC. Rothmund-Thomson syndromeD. Dyskeratosis CongenitaCorrect ChoiceE. Xeroderma PigmentosumDyskeratosis Congenita (also known as Zinsser-Engman-Cole syndrome) is thought to have twomodes of inheritance. The more common X-linked disorder is due to a mutation in the Dyskeringene, while the autosomal dominant form is due to a mutation in TERC, a telomerase RNAcomponent. Clinical features include reticulated gray-brown hyperpigmentation, paloplantarhyperkeratosis, alopecia, onychodystrophy, premalignant leukoplakia of any mucosal surface, andmental retardation 27
  28. 28. 97) Which of the following disorders is associated with delayed separation of the umbilical cord?A. Leukocyte adhesion deficiency type 1 (LAD-1)Correct ChoiceB. Myeloperoxidase deficiencyC. X-linked agammaglobulinemiaD. Severe combined immunodeficiency disorder(SCID)E. Immunedysregulation, polyendocrinopathy, enteropathy, x-linked (IPEX)LAD-1 manifests as a B2-integrin deficiency and often times presents as at birth with a delayedumbilical cord separation.98) Mucosal neuromas, pheochromocytoma and medullary thyroid carcinoma in a patient with amarfanoid body habitus is associated with which of the following gene defects?A. RET proto-oncogeneCorrect ChoiceB. STK11C. BHDD. MeninE. PTENThe RET proto-oncogene is mutated in Multiple Endocrine Neoplasia type II. Type IIb is describedabove. Other findings include rare parathyroid abnormalities, megacolon, thickened lips and thick,everted upper eyelids. Menin is associated with MEN type I, PTEN with Cowden disease, BHD withBirt-Hogg-Dube syndrome and STK11 with Peutz-Jeghers syndrome99) In a patient suspected of having multiple endocrine neoplasia type IIb, which lab test would beappropriate?A. Parathyroid hormoneB. CortisolC. CalcitoninCorrect ChoiceD. GlucagonE. CalciumMultiple endocrine neoplasia (MEN) syndrome type Iib, also called multiple mucosal neuromasyndrome is an autosomal dominant condition due to a defect in the RET protooncogene onchromosome 10q11.2. This rare condition is associated with mucosal neuromas on the tongue andlips, medullary thyroid carcinoma, pheochromocytoma, and gastrointestinal ganglioneuromatosis. Inaddition, patients can also present with a marfanoid habitus and facial dysmorphism. Mucosalneuromas can be a dermatologic clue to the underlying diagnosis as these lesions appear duringearly childhood and present as pink, pedunculated nodules. As the major cause of mortality in thesepatients is medullary thyroid cancer, which nearly all patients will have by early adulthood,aggressive screening, with serial calcitonin level, and prophylactic thyroidectomy are warranted.100) What is the gene defect in this condition, which is also called Mendes da Costa syndrome?A. keratin 1 and 10B. SPINK5 28
  29. 29. C. connexin 31Correct ChoiceD. SLURP-1E. connexin 26Mendes da COsta syndrome is also called Erythrokeratoderma Variabilis. It is an autosomaldominantly inherited due to a mutation in connexin 31 or connexin 30.3. It is characterized bytransient geographic patches of erythema and hyperkeratotic plaques101) The hair abnormality shown in the image is characteristic of which of the following diseases?A. TrichothiodystrophyCorrect ChoiceB. MonilethrixC. Bjornstad syndromeD. All of the options are correctE. Naxos diseaseThe hair abnormality shown is trichoschisis, clean breaks of the hair shaft which occurs intrichothiodystrophy. Also commonly seen is the "tiger-tail" banding pattern of the hair when placedunder polarized light. The other options do have hair shaft abnormalities, but not trichoschisis102) The treatment for acrodermatitis enteropathica is:A. Vitamin B12 supplementationB. Zinc supplementationCorrect ChoiceC. PhlebotomyD. Iron supplementationE. Vitamin B1 supplementationAcrodermatitis enteropathica is due to a defect in zinc absorption and will respond to zincsupplementation. Iron, Vitamin B1/12 supplementation will not result in improvement in thiscondition. Findings include periorificial, scalp, and acral dermatitis, scaling, vesicles/bullae, erosions,alopecia, diarrhea and stomatitis103) In patients with diffuse congenital hemangiomatosis, the most common site forextracutaneous involvement is the :A. BrainB. ThyroidC. LiverCorrect ChoiceD. LungsE. ColonDiffuse congenital hemangiomatosis is characterized by multiple hemangiomas with the liver beingthe most common extracutaneous site, followed by the lungs. Liver hemangioma may becomplicated by hepatomegaly, obstructive jaundice, and portal hypertension104) A deficiency in sialophorin, a surface glycoprotein, is thought to play a role in which geneticdisorder? 29
  30. 30. A. Bloom SyndromeB. Chediak-higashi syndromeC. Cornelia de Lange syndromeD. Werner syndromeE. Wiskott-aldrich syndromeCorrect ChoiceWiskott-Aldrich syndrome is an x-liked recessive disorder localized to Xp11.3. The gene involvedcodes for WAS, and the protein product has been implicated in lymphocyte and megakaryocytesignal transduction105) Sphenoid wing dysplasia is seen in:A. Tay SyndromeB. NF-1Correct ChoiceC. NF-2D. Mafucci syndromeE. Tuberous sclerosisSphenoid wing dysplasia is seen in neurofibromatosis type I. Patients with Tay syndrome have shortstature, patients with tuberous sclerosis have phalangeal cysts and periosteal thickening, patientswith Mafucci syndrome have enchondromas and short stature, and patients with NF-2 do not haveany characteristic musculoskeletal findings106) A patient Buschke-Ollendorff syndrome has osteopoikilosis and which cutaneous finding?A. Epidermal neviB. Café au lait maculesC. Waxy papules along the eyelidsD. Port wine stainE. Juvenile elastomaCorrect ChoiceBuschke-Ollendorf syndrome is an autosomal dominant syndrome associated with increased elasticfiber in the skin. Key features include dermatofibrosis lenticularis disseminata (also called juvenileelastomas) and osteopoikilosis107) Which of the following is NOT part of the Carney complex?A. Endocrine abnormalitiesB. Peg or conical teethCorrect ChoiceC. Pigmented skin lesionsD. Cardiac, cutaneous or mammary myxomasE. Primary pigmented nodular adrenocortical diseasePeg/conical teeth are not part of the Carney complex. This is found in incontinentia pigmenti andanhidrotic ectodermal dysplasia. The remaining skin findings are part of this complex sometimesknown as NAME syndrome. It consists of multiple, diffuse mucocutaneous lentigines, cardiac andsubcutaneous myxomas and endocrine abnormalities may be present. Other findings include:testicular tumors, thyroid disease, primary pigmented nodular adrenocortical disease,psammomatous melanotic schwannomas and hormone-secreting pituitary adenomas 30
  31. 31. 108) A patient presents with the multiple painful papules on the abdomen with pathology as shownin the image. They report that their father had similar skin lesions. What enzyme defect is the mostlikely cause?A. Steroid sulfataseB. homogentisic acid oxidaseC. glucocerebrosidaseD. alpha-galactosidaseE. fumarate hydrataseCorrect ChoiceFumarate hydratase has been implicated in familial multiple cutaneous leiomyomatosis. Steroidsulfatase is defective in x-linked ichthyosis, alpha-galactosidase in Fabry disease, homogentisic acidoxidase in alkaptonuria and glucocerebrosidase in Gaucher disease.109) Cutaneous osteomas are seen in which syndrome?A. Carney complexB. Albright hereditary osteodystrophy Correct ChoiceC. Gaucher’s syndromeD. Waardenburg syndromeE. LEOPARD syndromeAlbright hereditary osteodystrophy is caused by mutations in the Gs subunit of adenylate cyclase.There is calcification and ossification due to pseudohypoparathyroidism, absent 4th knuckle, andhypogonadism.110) What is the genetic defect of this autosomal dominant disorder?A. Calcium ATPase 2C1Correct ChoiceB. PTPN11C. SPINK5D. Calcium ATPase 2A2E. PTENHailey-Hailey is an autosomal dominant disorder that usually affects the intertriginous areas.Clinically, there is erythema and linear fissures of the axilla and groin. On pathology, thecharacteristic finding is dyskeratosis in a "dilapidated brick wall" pattern. The gene defectresponsible is calcium ATPase 2C1111) Primary pigmented nodular adrenocortical disease and psammomatous melanoticschwannomas are characteristic of which of the following syndromes?A. McCune-Albright syndromeB. Tuberous sclerosisC. Gaucher’s syndromeD. Hypomelanosis of Ito 31
  32. 32. E. Carney complex Correct ChoiceCarney complex is an autosomal dominant disorder caused by mutations in PRKAR1A (proteinkinase A regulatory subunit 1-alpha). Key features include cardiac, cutaneous and mammarymyxomas, pigmented skin lesions, endocrine abnormalities (pituitary, testicular, thyroid, etc),primary pigmented nodular adrenocortical disease, and psammomatous melanotic schwannomas112) A triangular-shaped lunula is a characteristic finding in which disease?A. incontinentia pigmentiB. Dariers diseaseC. dyskeratosis congenitaD. nail-patella syndromeCorrect ChoiceE. epidermal nevus syndromeNail-patella syndrome, also called hereditary osteo-onychodysplasia is a rare autosomal dominantcondition caused by a defect in the LMX1B gene. It is characterized by triangular lunulae,palmoplantar hyperhidrosis, renal dysplasia, glomerulonephritis, and hyperpigmentation of thepapillary margin of the iris, an ophthalmologic finding also known as Lester iris. Other nail findingsinclude micronychia with hemionychia, anonychia, and longitudinal fissures. Bony findings includeabsent or hypoplastic patella, posterior iliac horns, radial head subluxation, thickened scapulae, andscoliosis.Nail findings in Dariers disease include red and white longitudinal bands, subungual hyperkeratosisand V-shaped nicking of the distal nail plate. Dystrophic nails with longitudinal ridges, pterygium,and atrophic or absent nails can be found in dyskeratosis congenita. Dystrophic changes of the nailscan be seen in approximately 5-10% of patients with incontinentia pigmenti.113) A patient with renal cell carcinoma caused by mutations in fumarate hydratase deficiencylikely suffers which of the following conditions?A. Multiple endocrine neoplasiaB. Birt-Hogg-Dube syndromeC. Von-Hippel-Lindau syndromeD. Familial multiple cutaneous leiomyomatosis Correct ChoiceE. Cowden syndromeFamilial multiple cutaneous leiomyomatosis is an autosomal dominant condition caused bymutations in the fumarate hydratase gene. Clinically, there are multiple cutaneous leiomyomas,uterine leiomyomas and leiomyosarcomas, as well as renal cell carcinomas114) A patient presents with several light blue cyst-like lesions on the eyelid. They consult their listof problems and bring up plantar hyperkeratosis and dysplastic toenails. On oral exam, you notethat they have both upper and lower dentures. The patient relates that after losing their "babyteeth", only 3 teeth grew in their place. What syndrome does this person most likely have?A. Cowden syndromeB. Cronkhite-CanadaC. Hypohidrotic ectodermal dysplasiaD. Schopf-Schulz-PassargeCorrect ChoiceE. Gardner syndrome 32
  33. 33. Schopf-Schulz-Passarge syndrome is associated with hydrocystomas of the eyelids, hypotrichosis(near complete loss of hair early in life), hypodontia, nail abnormalities and multiple palmoplantareccrine syringofibroadenomas. The other listed syndromes do not fit the description above115) The presence of natal teeth and pincer nails suggests which disease entity?A. anhidrotic ectodermal dysplasiaB. pachyonychia congenitaCorrect ChoiceC. congenital syphillisD. thalidomide exposure in uteroE. incontinentia pigmentiPachyonychia congentia is an autosomal dominant condition characterized by a constellation offindings affecting ectodermal structures. These include the presence of natal teeth, steatocystomamultiplex, follicular hyperkeratosis of the knees, elbows and extensor extremities, eruptive vellushair cysts, and oral leukokeratosis which is not pre-malignant. In addition, nail findings includetwenty-nail dystrophy, subungual hyperkeratosis with increase transverse curvature ("pincer nails")and candidal paronychia. There are two forms of pachyonychia congenital: Type 1 (Jadassohn-Lewandowsky syndrome) caused by defects in keratin 6a and 16, and Type 2 (Jackson-Lawler type)caused by defects in keratins 6b and 17.Anhidrotic ectodermal dysplasia is associated with peg-shaped teeth, hypoanodontia, and a non-specific nail dystrophy. Likewise, incontientia pigmenti also is characterized by anodontia and peg-shaped teeth and dystrophic changes of the nail. Finally congenital syphilis is a well-recognizedcause of pegged teeth. Limb deformities are the most serious sequelae of thalidomide exposure inutero116) A patient with pseudoherpetic keratitis and a painful PPK would improve with a diet low in:A. ZincB. BiotinC. CytosineD. Tyrosine/PhenylalanineCorrect ChoiceE. GlycinePseudoherpetic keratitis and a painful PPK describes a patient with Richner-Hanhart syndrome(tyrosenemia type II). Treatment is with a diet low in tyrosine and phenylalanine. A diet low inglycine, cytosine, biotin or zinc would not be helpful in this syndrome117) A patient with multiple facial trichilemmomas is at risk of which of the following cancers?A. Basal cell carcinomaB. CylindromaC. Breast carcinoma Correct ChoiceD. Oral squamous cell carcinomaE. Acute leukemiaCowden syndrome (multiple hamartoma syndrome) is an autosomal dominant disorder caused bymutations in PTEN, a phosphatase that dephosphorylates tyrosine, serine, and threonine. Clinically,there are numerous facial trichilemmomas, oral papillomas, acral keratotic papules, scleroticfibromas, breast fibroadenomas and adenocarcinomas, thyroid adenomas and adenocarcinomas,and hamartomatous polyps of the gastrointestinal tract 33
  34. 34. 118) Which of the following signs is not a criteria for the diagnosis of Neurofibromatosis type I?A. Sphenoid dysplasiaB. Axillary frecklingC. Greater than 5 café-au-lait maculesD. Optic gliomasE. Bilateral vestibular schwannomasCorrect ChoiceBilateral vestibular schwannomas are related to type II neurofibromatosis. The remaining optionsare diagnostic criteria for NF-1.119) Patients with homocystinuria are deficient in:A. TransglutaminaseB. Lysyl oxidaseC. Cystathionine synthetaseCorrect ChoiceD. Alpha galactosidase AE. Steroid sulfataseHomocystinuria is an autosomal recessive disease caused by a deficiency of cystathioninesynthetase. Manifestations of this condition may include mental retardation, marfanoid habitus,malar flush, ectopic lentis, embolic phenomena and leg ulcers120) A patient presents with bilateral retinal hemangioblastomas and a capillary malformation onher neck. Which gene mutation is most likely?A. MFH1B. PTH/PTHrP type I receptorC. VEGF receptor-3D. EndoglinE. VHLCorrect ChoiceThese findings are most characteristic of Von Hippel-Lindau syndrome. VHL is a tumor suppressorgene which is mutated in this syndrome. Other findings include: renal and pancreaticcysts/carcinoma, pheochromocytoma, and cerebellar/other CNS hemangioblastomas. Endoglin isdefective in Osler-Weber-Rendu, PTH/PTHrP type I receptor in Maffucci syndrome, VEGF receptor-3in Nonne-Milroy disease (hereditary lymphedema) and MFH1 in lymphedema and ptosis syndrome121) The gene defect in LEOPARD syndrome is:A. ATMB. KIP2C. PTPN11 Correct ChoiceD. PRKAR1AE. Neurofibromin 34
  35. 35. PTPN11 gene is mutated in LEOPARD syndrome. This syndrome consists of the complex ofLentigines, EKG abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia,Retardation of growth and Deafness. PRKAR1A is associated with the Carney complex of diseases.KIP2 is found in 15% of cases of Beckwith-Wiedermann syndrome. ATM is mutated in ataxiatelangectasia syndrome and Neurofibromin in Neurofibromatosis type I.122) Hereditary Hemorrhagic Telangiectasia syndrome is transmitted in an autosomal dominantfashion and can have two variants. Type I is linked to defects in HHT1, the endoglin gene. Type II islinked to defects in HHT2, the ALK1 gene. What feature that differentiates type I from type IIclinically?A. Type I families have an increase incidence of pulmonary arteriovenous fistulasCorrect ChoiceB. None of the answers are correctC. Type I families have an increased incidence of hepatic arteriovenous malformationsD. Type II families have an increased incidence of pulmonary arteriovenous fistulasE. Type II families have a decreased incidence of hepatic arteriovenous malformationsThere is an increased incidence of pulmonary arteriovenous fistulas in HHT type I. Type II has anincreased incidence of hepatic arteriovenous malformations.123) Connexin 30 (GJB6 gene) is defective in which of the following syndromes?A. Vohwinkel syndromeB. Erythrokeratoderma variabilisC. Clouston syndromeCorrect ChoiceD. KID syndromeE. Vohwinkel syndrome variantClouston syndrome is associated with a defect in Connexin 30 (GJB6 gene). Findings includepalmoplantar keratoderma with transgradiens, dystrophic nails, sparse hair with absent body,eyelash, eyebrow hair after puberty. KID syndrome and Vohwinkel syndrome are associated with adefect in Connexin 26 (GJB2). Vohwinkel syndrome variant is associated with a loricrin defect.Erythrokeratoderma variabilis has mutations in Connexin 31 (GJB3) and 30.3(GJB4).124) What protein is deficient in the condition shown?A. Desmoglein 3B. SPINK5C. Calcium ATP’ase IIA2D. Calcium ATP’ase IIC1Correct ChoiceE. PEX-7The picture shown is Hailey-Hailey disease. This is an autosomally dominant condition with a defectin Calcium ATP’ase IIC1. On H&E stain, an acantholytic “dilapidated brick wall” appearance is seen.Calcium ATP’ase IIA2 is defective in Darier’s Disease, PEX-7 in autosomal recessive type Conradi-Hunermann disease, SPINK5 in Netherton’s disease and Desmoglein 3 in pemphigus vulgaris 35