Genodermatoses

Question 1

What are the characteristics of Albinism?

Answer 1

• hypopigmentation/depigmentation disorder
• gene: variable deficiency of melanin
• Three types, Type III has most pigment because still produces pheomelanin since defect is in TYRP1. Type I defect in tyrosinase, makes no melanin

Question 2

What are the characteristics of Peutz-Jeghers syndrome?

Answer 2

AKA Periorificial lentiginosis-pigmented macules on mucosal surfaces
Gastrointestinal polyps: 1st-3rd decade of life, more in small intestines
Risk for various malignancies: pancreas, ovaries, breast
Autosomal dominant
40% spontaneous mutations
1:25,000-50,000
Gene defect: STK11/LKB1 gene, tumor suppressor gene

Question 3

What are the characteristics of Gardner’s Syndrome?

Answer 3

Autosomal dominant
M=F 1:14,000
Gene defect: APC-adenomatous polyposis coli gene, tumor suppressor gene
Clinical features
-Lots of Epidermal cysts
-Osteomas –abnormal bone growth where its not supposed to be
-Odontomas-abnormal dental issues, supernumerary teeth
-Congenital hypertrophy of retinal pigment epithelium (CHRPE)
-Colon Cancer: Very high risk!
-Children with multiple cysts and FH of colon cancer should be eval with eye exam, stool guaiacs, sigmoidoscopy/colonoscopy
-Actual indication for prophylactic colectomy

Question 4

What are the characteristics of xeroderma pigmentosum?

Answer 4

a. Autosomal recessive, M=F
b. Rare in Europe and USA, more common in Japan
c. Gene defect: XPA, B, C, D, E, F, G
i. Defective DNA excision repair, DNA helicase, or DNA binding protein for repair and transcription
d. Clinical features
i. First sign of disease: acute sun sensitivity
ii. Photodistributed blisters and erythema
iii. Early signs of disease: mottling and freckling on the face of toddler
iv. Further progression: narrowing of nares and mouth. Looks like old person
v. 1000x risk of skin cancer
vi. 8 years old=avg age of first skin cancer
vii. Eyes: progessive photophobia, conjunctivitis, ectropion, corneal vascularization, opacification, BCC, melanoma
viii. Neurologic (20%): progressive degradation

Question 5

What are the characteristics of neurofibromatosis I?

Answer 5

a. Autosomal dominant, 50% due to somatic mutation
b. 1:2500-3500 births
c. gene: neurofibromin, c17
d. clinical features
i. café au lait macules: hyperpigmented patches, non-specific
ii. neurofibromas
more numerous with age
disfiguring
buttonhole phenomenon: push in, it will retract and can feel the nerve defect at the center
iii. Crowe’s sign: axillary and inguinal freckling
iv. Plexiform Neurofibromas:
“Bag of worms”
potential for malignant degeneration
v. Lisch Nodules
Melanocytic harmartomas of the iris
Often need a slit-lamp exam to visualize
Present in 94% of patients after age 6, can be helpful in diagnosis
vi. Optic gliomas: benign CNS tumor
vii. Osseous changes: thinning of the long bone cortex, leading to anterior tibial bowing and pseudoarthrosis, sphenoid wing dysplasia, kyphoscoliosis
e. Diagnositic criteria, need two or more of:
6+ café au lait macules
axillary/inguinal freckling
2+ NFs or one plexiform NF
optic glioma
osseous lesions
2+relatives

Question 6

What are the characteristics of neurofibromatosis II?

Answer 6

a. Autosomal dominant
b. Gene: Schwannomin or merlin: c22
c. Bilateral acoustic neuromas
d. Cutaneous features
i. NFs
ii. Rare café au lait macules
iii. No freckling

Question 7

What are the characteristics of Tuberous Sclerosis?

Answer 7

Autosomal dominant
50% are due to spontaneous mutation
Gene defect: TSC-1 (hamartin), TSC-2 (tuberin)
-Clinical Triad: Adenoma sebaceum, Mental deficiency, Epilepsy
-Adenoma sebaceum: symmetric yellow to reddish papules on cheek, nose, forehead
-Shagreen patch: Connective tissue nevus in lumbosacral area
-Koenen’s tumors: small periungal fibromas
-hypomelanotic macules: ash leaf shape
CNS system, renal, cardiac, pulmonary also involved

Question 8

What are the characteristics of Marfan’s Syndrome?

Answer 8

Autosomal Dominant
defect: Fibrillin- component of microfibril sheath around elastin in dermis
skin: strae distensae, elastosis perforans serpiginosa
MS: tall, long arms, arachynodactyly, sternum caves in or out, high arched palate, loose jointedness
CV: ascending aortic aneurysms, mitra valve prolapse
ocular: myopia, retinal detachement, ectopia lentis

Question 9

What are the characteristics of dystrophic epidermolysis bullosa (EB)?

Answer 9

defect: type VII collagen, autosomal dom and recessive
Gene: COL7A1
Severe subepidermal blistering disease
extremely fragile skin, scars with milia, “mitten deformity”, mucosal involvement–>esophageal stenosis and strictures
avg age SCC: 20

Question 10

What are the characteristics of Ehlers-Danlos Syndrome?

Answer 10

Defect: collagen III
-excessive stretching and fragility of skin
-hyperextensible joints
-Gorlin’s sign: tongue to nose
-Molluscoid pseudotumors: fish mouth appearance of scars
-

Question 11

What are the characteristics of Fabry’s Disease?

Answer 11

X linked recessive
gene defect: a-galactosidase A, Accumulation of globotriacyclceramide-neutral glycosphingolipid
-angiokeratomas
-hypo/anhidrosis: lack of sweating
-PNS: painful crises on hands and feet
-CV problems
-Kidney: end stage renal disease by 30, maltese crosses (lipid globules in urine)
Also CNS, eye, ear, problems