Genodermatoses

P R E S E N T E D B Y
D R R A V I N D R A M A H A N T H I
1 S T M D S
D E P T O F O R A L P A T H O L O G Y & M I C R O B I O L O G Y
Genodermatoses

contents
 Introduction
 Classificati0n
 Ectodermal Dysplasia
 White Sponge Nevus
 Hereditary Benign Intraepithelial Dyskeratiosis
 Xeroderma Pigmentosum
 Hereditary Mucoepithelial Dysplasia
 Darier’s Disease
 Peutz-jeghers syndrome
 Hereditary Hemorrhagic Telangiectasia
 Ehlers-danlos Syndromes
 Tuberous Sclerosis
 Multiple Hamartoma Syndrome
 Epidermolysis Bullosa
 Conclusion

Introduction
 Genodermatoses are an inherited skin disorder
associated with structure and function.
 Several genodermatoses present with multisystem
involvement lead to increased morbidity and
mortality.
 accompanied by various systemic manifestations.

Genokeratoses:
Some of the systemic manifestations are characterized
particularly by alterations in the normal
keratinization process. These have been specifically
referred to as Genokeratoses.

Classification
 There is no universally accepted classification of
these dermatologic disorders.
Based on etiology:
 Chromosomal
 Single gene
 Polygenetic

ECTODERMAL DYSPLASIA
 A group of inherited conditions in which two or more
ectodermally derived anatomic structures fail to
develop
 Classified based on clinical features
 Hypohydrotic ED -X linked recessive
 Hydrotic ED-autosomal dominant
The various types of this disorder may be
inherited in anyone of several genetic patterns.

Hypohidrotic ectodermal dysplasia:
 X-linked - mapped in the proximal area of the long
arm of band Xq-12-q13.1
 Decreased expression of the epidermal growth factor
receptor. Gene ED1 is responsible.
 Autosomal recessive - phenotypically
indistinguishable from the X-linked form.
 Gene is located at dl (downless) locus

Hidrotic ectodermal dysplasia
 GJB6 is the causative gene.
 This encodes for connexin 30.
 Located at pericentromeric region of chromosome 13q.
 For patients with cleft lip/palate-mutation PVRL 1,
encoding a cell to cell adhesion molecule/herpes virus
receptor.
 Reduction in number of sweat gland, hair follicle, and
sebaceous gland. Salivary glands may show ectasia of
ducts and inflammatory changes.

CLINICAL FEATURES:
 A male predominance is usually seen. (X-linked
inheritance pattern).
 Affected individuais typically dispiay heat
intolerance because of a reduced number of sweat
glands.
 Rarely death results from the markedly elevated
body temperature.

 Fine, sparse blonde hair,
 Reduced density of eyebrow
and eyelash hair
 The periocular skin may
show a fine wrinkling with
hyperpigmentation
 Midface hypoplasia resulting
in protuberant lips.
 Xerostomia (because the
salivary glands are
ectodermally derived)
 The nails may also appear
dystrophic and brittle.

ORAL MANIFESTATIONS:
 Oligodontia or hypodontia.
 Anodontia has also been
reported, but this appears to be
uncommon.
 Characteristically abnormal
crown shapes
 The incisor crowns usually
appear tapered, conical or
pointed.
 The molar crowns are reduced in
diameter.

Histologic features:
 shows a decreased number of sweat glands and hair
follicles
 adnexal structures are hypoplastic and malformed
Treatment:
 genetic counseling for parents and the patient •
dental problems are managed by prosthetic
replacement of dentition

WHITE SPONGE NEVUS
 CANNON’S DISEASE;
 FAMILIAL WHITE FOLDED DYSPLASIA
Etiology:
 Autosomal dominant trait, described by cannon in
1935
 Defect in normal keratinization of oral mucosa.
 Keratin 4 and keratin 13 is specifically expressed in
the spinous layer.
 Mutations in either of these Keratin genes
responsible for the clinical manifestations.

Clinical features :
 Lesions appear at birth or in
early age
 symmetric, thickened,
white, corrugated or velvety
diffuse plaques affect the
buccal mucosa bilaterally
 ragged white areas which
can be removed by gentle
rubbing without bleeding
 Patients are asymptomatic

Histopathologic features:
 Prominent
hyperparakeratosis.
 Marked acanthosis with
intracellular edema of the
spinous layer.
 Parakeratin plugging
running deep into the
spinous layer.

Exfoliative cytology
 An eosinophilic
condensation in the
perinuclear region of the
cells in the superficial
layers of the epithelium.
 Tangled masses of keratin
tonofilaments.
Treatment and Prognosis
 Because this is a benign
condition, no treatment is
necessary. The prognosis is
good.

HEREDITARY BENIGN INTRAEPITHELIAL
DYSKERATOSIS
 Witkop Von Sallman Syndrome
 rare autosomal dominant genodermatosis
 affects descendants of native American, black and
white people who originally lived in North Carolina.
 Autosomal dominant transmission.
 A segment of DNA localized at 4q35 is duplicated
resulting in triple alleles for 2 linked markers
suggesting that gene duplication is responsible for
the disorder develop during childhood.

Clinical features
 Lesions usually develop during childhood, affect oral
and conjunctival mucosa.
 Oral lesions - similar to white sponge nevus

 Most interesting feature of
HBID- ocular lesions, which
begin to develop very early in
life.
 Thick, opaque, gelatinous
plaques affecting the bulbar
conjunctiva adjacent to the
cornea.
 Patients may experience
tearing, photophobia, and
itching of the eyes.
 Blindness may result from the
induction of vascularity of the
cornea.

Histopathologic features
 prominent parakeratin
production in addition to
marked acanthosis.
 peculiar dyskeratotic process,
similar to that of Darier’s
disease,
 With this dyskeratotic process,
an epithelial cell appears to be
surrounded or engulfed by an
adjacent epithelial cell,
resulting in the so-called “cell-
within- a- cell” phenomenon.

 Because HBID is a benign condition, no treatment is
generally required or indicated for the oral lesions.
 If superimposed candidiasis develops ,an antifungal
medication can be used.
 Patients with symptomatic ocular lesions should be
referred to an ophthalmologist.
 Typically the plaques that obscure vision must be
surgically excised.
 This procedure, however, is recognized as a temporary
measure because the lesions often recur.

PACHYONYCHIA CONGENITA
 A group of rare genodermatoses
 Usually inherited as an autosomal dominant trait.
 Mutations of genes that encode for keratin 6a, 6b,16
or 17.
 Specific mutations in the keratin 16 gene-
Jadassohn–Lewandowsky type. Mutations of the
keratin 17 gene are associated with the Jackson-
Lawler form.

Clinical features
 The nails are dramatically affected in most patients.
 The free margins of the nails are lifted up because of
an accumulation of keratinaceous material in the nail
beds.
 The oral lesions are seen in the Jadassohn–
Lawandowsky form.
 Whitish plaques on the mucosa of the cheeks,
tongue.

 Marked hyperparakeratosts and acanthosis with
perinuclear clearing of the epithelial cells.
 Because the oral lesions of pachyonychia congenita
show no apparent tendency for malignant
transformation, no treatment is required.
 The nails are often lost or may need to be surgically
removed because of the deformity.
 Patients should receive genetic counseling;

DYSKERATOSIS CONGENITA
 COLE-ENGMAN SYNDROME
 ZINSSER-COLE-ENGMAN SYNDROME
 a rare genodermatosis
 usually inherited as an X- linked recessive trait.
 Mutations in the DKC1 gene.
 The mutated gene appears to disrupt the normal
maintenance of telomerase.

Clinical features
 Striking male predilection. (X-linked recessive trait)
 Skin hyper pigmentation develops, affecting the face,
neck, and upper chest.
 Dysplastic changes of the nails.
 Intraorally, the tongue and buccal mucosa develop
bullae; these are followed by erosions and eventually
leukoplakic lesions.
 The leukoplakic lesions are considered to be
premalignant.
 Thrombocytopenia is usually the first hematologic
problem that develops. Followed by anemia. Ultimately
aplastic anemia develops.

 Hyperorthokeratosis with epithelial atrophy.
 As the lesions progress, epithelial dysplasia develops until
frank squamous cell carcinoma evolves.
Treatment and Prognosis:
 The discomfort of the oral lesions is managed
symptomatically.
 And careful periodic oral mucosal examinations are
performed to check for evidence of malignant transformation.
Routine medical evaluation is warranted to monitor the
patient for the development of aplastic anemia.
 Selected patients may be considered for allogeneic bone
marrow transplantation once the aplastic anemia is identified.

XERODERMA PIGMENTOSUM
 A rare genodermatosis in which numerous cutaneous
malignancies develop at a very early age.
 Inherited as an autosomal recessive trait
 Caused by defects in the excision repair and /or post
-replication repair mechanism of dna.
 Mutations in the epithelial cells occur, leading to the
development of skin cancer.
 Inability of the epithelial cells to repair ultraviolet
(UV) light-induced damage.
 Markedly increased tendency to sunburn.

Clinical features:
 Increased tendency to sunburn.
 Skin changes-atrophy, freckled pigmentation, and patchy
depigmentation
 Early childhood-actinic keratoses develop
 Lesions quickly progress to squamous cell carcinoma, with
basal cell carcinoma also appearing
 Non-melanoma skin cancer develops during the first decade
of life.
 Melanoma- about 5% of patients, but it evolves at a later time.
 Oral manifestations-occur before 20 years of age- squamous
cell carcinoma of the lower lip ,tip of the tongue.

 Histopathologic features of xeroderma pigmentosum are
relatively nonspecific
 Cutaneous premalignant lesions and malignancies that
occur are microscopically indistinguishable from those
observed in unaffected patients.
Treatment
 To avoid sunlight and unfiltered fluorescent light
 To wear appropriate protective clothing and sunscreens
 Topical chemotherapeutic agents (e.G. 5- fluorouracil)
may be used to treat actinic keratoses.

Hereditary Mucoepithelial Dysplasia
 Rare disorder
 autosomal dominant trait
 Mucosal cells do not develop in a normal fashion –
hence the name dysplasia
 No increased risk of malignancy

Clinical features
 Both cutaneous and mucosal
abnormalities present
 Sparse, coarse hair with non
scarring alopecia
 Ocular lesions-
Photophobia,cataracts,ker
atitis,nystagmus,impaired vision
 Rough ,dry skin,prominent
perineal rashes appearing in
infancy
 Pulmonary complications-
recurrent pneumonia,
cavitations of lung parenchyma

Oral manifestations
 striking , well demarkated
fiery red erythema of hard
palate
 Attached gingiva, tongue
mucosa-Less involved
 Mucosal alterations
typically asymptomatic
 Nasal,conjunctival,vaginal
cervical,urethral mucosa
involved

Histopathology
 Shows epithelium with minimal keratinisation and
disorganized maturisation pattern
 Relatively high N/C ratio of epithelial cells
 No significant nuclear or cellular pleomorphism
 Cytoplasmic vacuolations seen as grey inclusions,
more in cytologic smears
 Ultrastructurally ,lesional cells have reduced no. of
desmosomes and gap junctions

DARIER’S DISEASE
 KERATOSIS FOLLICULARIS ,DYSKERATOSIS
FOLLICULARIS; DARIER-WHITE DISEASE.
 Uncommon genodermatosis
 Striking skin involvement and relatively subtle oral
mucosal lesions.
 Inherited as an autosomal dominant trait
 mutations in atp2a2 gene
 lack of cohesion among the surface epithelial cell
characterizes this disease
 Mutation of a gene that encodes an intracellular calcium
pump- cause for abnormal desmosomal organization in
the affected epithelial cells.

Clinical features
 Erythematous, pruritic, papules on
skin of trunk and the scalp
 Develop during the second decade of
life
 Accumulation of keratin, producing a
rough texture
 A foul odor may be present as a result
of bacterial degradation of the keratin
 Palms and soles often exhibit pits and
keratoses
 Nails show longitudinal lines, ridges,
or painful splits and sub ungual
keratosis

oral lesions
 Asymptomatic, discovered on routine
examination.
 consist of multiple, normal- colored
or white, flat topped papules
 result in a cobblestone mucosal
appearance
 affect the hard palate and alveolar
mucosa
 buccal mucosa or tongue may be
involved
 palatal lesions may resemble
inflammatory papillary hyperplasia or
nicotine stomatitis

 Shows a dyskeratotic process
 Characterized by central keratin
plug that overlies epithelium
exhibiting a suprabasilar cleft.
 Intraepithelial clefting
phenomenon, known as
acantholysis.
 Rete ridges appear narrow,
elongated, and “test tube” shaped.
 Epithelium reveals varying
numbers of two types of
dyskeratotic cells,
 Corps ronds (round bodies) or
grains (resemble cereal grains).

 the condition is not premalignant or otherwise life
threatening, genetic counseling is appropriate.
 Photosensitive patients should use a sunscreen, and all
patients should minimize unnecessary exposure to hot
environments.
 For relatively mild cases, keratolytic agents may be the
only treatment required.
 For more severely affected patients, systemic retinoids
are often beneficial

PEUTZ-JEGHERS SYNDROME
 relatively rare but well recognized condition, having
a prevalence of approximately 1 in 20,000 births.
 The syndrome is generally inherited as a n autosomal
dominant trait, although 35 % of cases represent new
mutations.
 Mutation of a gene known as LKBI, which encodes
for a serine/ threonine kinase.

Clinical Features
 Usually develop early in childhood and involve the
periorificial areas (e.g., mouth, nose, anus, genital
region
 The lesions resemble freckles , but they do not wax
and wane with sun exposure.
 The intestinal polyps (The jejunum and ileum are
most commonly affected.)
 Gastrointestinal adenocarcinoma develops in 2%
to 3% of affected patients.

Oral lesions
 essentially represent an
extension of the perioral
freckling.
 These 1- to 4-mm brown to
blue-gray macules primarily
affect the vermilion zone, the
labial and buccal mucosa , and
the tongue and are seen in
more than 90 % of these
patients.
 The number of lesions and the
extent of involvement can vary
markedly from patient to
patient

Histopathologic Features
 Slight acanthosis of the epithelium with elongation
of the rete ridges.
 No apparent increase in melanocyte number is
detected by electron microscopy.
 But the dendritic processes of the melanocytes are
elongated.
 Furthermore the melanin pigment appears to be
Retained in the melanocytes rather than being
transferred to adjacent keratinocytes.

 Patients with Peutz-Jeghers syndrome should be
monitored for development of intussusception or
tumor formation.
 Genetic counseling is also appropriate.

Hereditary Hemorrhagic Telangiectasia
 OSLER-WEBER-RENDU SYNDROME
 Uncommon mucocutaneous disorder
 HHTI -caused by a mutation of endoglin gene on
chromosome 9
 HHT2- ALK-1 (activin receptor-like kinase-1)
mutation
 HHT1 -more pulmonary involvement, HHT2 -
milder disease of later onset.

Clinical features
 Diagnosed initially because of epistaxis.
 Nasal and oropharyngeal mucosa exhibit numerous scattered
red papules
 Small collections of dilated capillaries (telangiectasias) close
to the surface of the mucosa.
 Found on the vermilion zone of the lips, tongue, buccal
mucosa
 Lesions distributed throughout the gastrointestinal mucosa,
the genitourinary mucosa, conjunctival mucosa
 Chronic iron-deficiency anemia
 Arteriovenous fistulas in the lungs, liver, or brain
 Predisposition to brain abscess

Oral manifestations
 These telangiectatic vessels are most frequently
found on the vermilion zone of the lips, tongue, and
buccal mucosa.
 Although any oral mucosal site may be affected.
 Superficially located collection of thin walled
vascular spaces.

 a superficially located collection of thin-walled vascular
spaces that contain erythrocytes.
 For mild cases of HHT. no treatment may be required.
 Moderate cases may be managed by selective cryosurgery
or electrocautery of the most bothersome of the
telangiectatic vessels.
 More severely affected patients. particularly those
troubled by repeated episodes of epistaxis may require a
surgical procedure at the nasal septum(septal
dermoplasty).

EHLERS-DANLOS SYNDROMES
 A group of heterogeneous inherited connective tissue
disorders
 Problems attributed to the production of abnormal
collagen.

Types of EHLERS-DANLOS SYNDROMES

 Defects of type I,III and V collagen
 Hyper elasticity of the skin and cutaneous fragility
 Vascular type of ehlers-danlos (ecchymotic type)-
extensive bruising that occurs with everyday trauma
 Ehlers-danlos syndrome (type VIII) -dental
manifestations as a hallmark feature
 Marked periodontal disease activity at a relatively
early age

unusual healing
response occurs with
relatively minor injury
to the skin termed
papyraceous scarring
(resembles crumpled
cigarette paper)

oral manifestations
 Include the ability of 50% of these patients to touch
the tip of their nose with their tongue (gorlin sign)
 Easy bruising and bleeding during minor
manipulations of the oral mucosa
 Oral mucosal friability is present
 Tendency for recurrent subluxation of TMJ

 the various types of this syndrome show a variety of
inheritance patterns,
 So an accurate diagnosis is required so that
appropriate genetic counseling can be provided.

TUBEROUS SCLEROSIS
 EPILOIA; BOURNEVILLE-PRINGLE SYNDROME
 Uncommon syndrome
 Classically characterized by mental retardation,
seizure disorders, and angiofibromas of the skin.
 Two thirds of the cases are sporadic

 Facial angiofibromas appear as
multiple, smooth-surfaced
papules and occur primarily in
the nasolabial fold area.
 Similar lesions, called ungula
or periungual fibromas, are
seen around or under the
margins of the nails.
 Two other characteristic skin
lesions are
 Connective tissue hamartomas
–shagreen patches
 Ovoid areas of
hypopigmentation -ashleaf
spots.

CNS manifestations
 include seizure disorders and mental retardation
 rare tumor of the heart muscle- cardiac
rhabdomyoma
 hamartomatous proliferations in the CNS develop
into the potato-like growths “tubers” seen at autopsy.
 angiomyolipoma -Another hamartomatous type of
growth related to this disorder occurs primarily in
the kidney.

Oral manifestations
 Include developmental
enamel pitting on the facial
aspect of the anterior
permanent dentition
 Fibrous papules seen on the
anterior gingival mucosa
 Lips, buccal mucosa, palate,
and tongue may be involved
 Radiolucencies of the jaws
that represent dense fibrous
connective tissue
proliferations

Radiologic features-
 radio lucent jaw lesions consist of dense fibrous
connective tissue -resembles desmoplastic fibroma
or simple type of central odontogenic fibroma.

Histopathologic features:
 Shows a nonspecific fibrous hyperplasia.
 A benign aggregation of delicate fibrous connective tissue
 Characterized by plump, uniformly spaced fibroblasts
with numerous interspersed thin-walled vascular
channels
Treatment and prognosis
 The management of the seizure disorder with
anticonvulsant agents.
 Periodic mri of the head may be done to screen for intra
cranial lesions, whereas ultrasound evaluation is
performed for evaluation of kidney involvement.

MULTIPLE HAMARTOMA SYNDROME
 COWDEN SYNDROME
 A rare condition has important implications for the
affected patient
 Malignancies develop in a high percentage of these
individuals.
 Inherited as autosomal dominant
 Mutation of the pten (phosphate and tensin homolog
deleted on chromosome 10) gene

Cutaneous manifestations
 develop during the second decade of life
 skin lesions appear as multiple, small papules, primarily
on the facial skin, especially around the mouth, nose, and
ears
 Microscopically these papules represent hair follicle
hamartomas -trichilemmomas
 acral keratosis- a warty appearing growth that develops
on the dorsal surface of the hand
 palmoplantar keratosis- a prominent callus like lesion
on the palms or soles.

Diagnosis
 The diagnosis is based on the finding of two of the
following three signs:
 Multiple facial trichilemmomas
 Multiple oral papules
 Acral keratoses A positive family history is also
helpful in confirming the diagnosis.

 Histopathologic features of the oral lesions are rather
nonspecific, essentially representing fibroepithelial
hyperplasia
 Other lesions associated with this syndrome have
their own characteristic histopathologic findings,
depending on the hamartomatous or neoplastic
tissue origin.

oral lesionsoral lesions
 Mutiple papules affecting the gingiva, dorsal tongue,
and buccal mucosa.
 Other oral findings -higharched palate, periodontitis,
 Extensive dental caries
Treatment and Prognosis:
Some investigators recommend bilateral prophylactic
mastectomies as early as the third decade of life for
female patients because of the associated increased
risk of breast cancer.

EPIDERMOLYSIS BULLOSA
 A heterogeneous group of inherited blistering
mucocutaneous disorders.
 A specific defect in the attachment mechanisms of the
epithelial cells, either to each other or to the underlying
connective tissue.
 Depending on the defective mechanism of cellular
cohesion, there are four broad categories:
 EB Simplex- Keratin 5,14
 EB Junctional- α3, β3,r2
 EB Dystrophic -Oral lesions are most common, type VIII collagen
 EB Hemidesmosome- plectin,type XVII collagen, α6β38

Clinical features
 Dystrophic forms of epidermolysis
bullosa -an autosomal dominant
 Initial lesions are vesicles or bullae
 Seen early in life and develop on
areas exposed to low-grade, chronic
trauma, such as the knuckles or
knees.
 The bullae rupture, resulting in
erosions or ulcerations that
ultimately heal with scarring.
 Appendages such as fingernails may
be lost.

 Generalized recessive dystrophic epidermolysis bullosa
represents one of the more debilitating forms of the
disease.
 Vesicles and bullae form with even minor trauma.
 Hand function is often greatly diminished resulting in
fusion of the fingers into a mitten like deformity.
 Bulla and vesicle formation is induced by virtually any
food having some degree of texture.
 Even with a soft diet, the repeated cycles of scarring often
result in microstomia and ankyloglossia.
 Carious destruction of the dentition at an early age is
common

oral manifestations
 Typically mild
 Gingival erythema and tenderness
 Gingival recession and reduction in the depth of the
buccal vestibule.

 Features of epidermolysis bullosa
vary with the type being examined
 Simplex form shows intraepithelial
clefting by light microscopy.
 Junctional and dystrophic forms
show subeptithelial clefting.
 Electron microscopy-reveals
clefting at the level of the lamina
lucida of the basement membrane
in the junctional forms
 Below the lamina densa of the
basement membrane in dystrophic
forms.

Treatment and prognosis:
 Treatment of epidermolysis bullosa varies with the type.
 For milder cases no treatment other than local wound
care may be needed.
 Sterile drainage of larger blisters and the use of topical
antibiotics.
 For the more severe cases Intensive management with
oral antibiotics may be necessary if cellulitis develops
 Despite intensive medical care, some patients die as a
result of infectious complications.

Conclusion
 The genetic mysteries underlying several common
genodermatoses solved by gene identification strategies.
 Some innovative methods need to be elucidated at the
molecular level.
 The study of dermatoses affecting oral cavity is important
because of the role which the dentist plays in the
diagnosis, and treatment of these lesions.
 It is especially important for the dentist to recognize
dermatoses that exhibit concomitant lesions of the oral
mucous membrane.
 The dentist should be familiar with them so that he may
either institute appropriate treatment or refer the patient
to the proper therapist.

REFFERENCES
 Neville, Oral and Maxillofacial Pathology, First south
asia edition.
 Shafer`s textbook of oral pathology 6th edition.
 Gnananandar G, Rajesh E, Babu N, Krupaa J.
Genodermatoses. Journal of Pharmacy and Bioallied
Sciences. 2015;7(5):205.

Genodermatoses

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