Genodermatoses

Question 1

Genodermatoses

Answer 1

• Inherited skin conditions due to genetic disorders

- Often involves many organ systems

Question 2

Albinism

Answer 2

• Hypopigmentation, autosomal recessive
• Variable deficiency in melanin
• 3 types (most to least severe): tyrosinase negative (type I), P gene/P protein negative (type II), tyrosinase related protein negative (type III)
• Most severe have lowest melanin levels, least severe have higher melanin levels
• Type III albinos can still produce pheomelanin, but not eumelanin

Question 3

Peutz-Jeghers syndrome

Answer 3

• Periorifacial lentiginosis (sun spots) and GI polyps, risk for various malignancies
• Autosomal dominant but often spontaneous mutations
• Deficiency in tumor suppressor gene (serine/threonine kinase, STK11)
• See pigmented macules early on in life (usually mucosal surfaces and extremities)
• Polyps begin in 1st-3rd decade of life, usually in small intestine
• Can develop abdominal pain/bleeding and anemia, followed by obstruction
• Adenocarcinoma may develop
• Other common cancers: breast, ovarian, pancreatic

Question 4

Gardner’s Syndrome

Answer 4

• Autosomal dominant, mutation in tumor suppressor gene (APC)
• Develop epidermal cysts (lots of them), osteomas, odontomas (dental tissue), congenital hypertrophy of retinal pigment epithelium (CHRPE)
• Very high risk of colon cancer (prophylactic colectomy)

Question 5

Xeroderma Pigmentosum

Answer 5

• Autosomal recessive, defective DNA excision repair, DNA helicase, or DNA BP for repair and transcription
• Acute sun sensitivity, photoditributed blisters and erythema
• Young children begin to look old; mottling and freckling of skin, narrowing of nares and mouth
• 1000x increased risk of skin cancer (all 3 types)
• Eyes and CNS have problems as well (degenerate quickly)

Question 6

Neurofibromatosis I

Answer 6

• Autosomal dominant, 50% due to somatic mutation (on chrom 17: name has 17 letters)
• Early signs: hyperpigmented patches at young age (cafe-au-lait macules, large)
• Neurofibromas become more numerous and disfiguring over time. Have buttonhole phenomenon
• Axillary and inguinal freckling (crowe’s sign) are early detection
• Plexiform neurofibromas (large bag of worms) potential for malignant degeneration
• Lisch nodules: melanocytic hamartomas of the iris in most patients after age 6
• Have bending of bones, optic gliomas
• Dx requires at least 2 or more of the previous findings

Question 7

Neurofibromatosis II

Answer 7

• Autosomal dominant (chrom 22) causing bilateral acoustic neuromas
• Schwann cell neoplasm around cranial nerve 8 (hearing)
• Cutaneous features: neurofibromas (no cafe-au-lait, no freckling)
• Neurofibromas are peripheral nerve sheath tumors

Question 8

Tuberous sclerosis

Answer 8

• autosomal dominant, but half due to spontaneous mutation
• clinical triad: adenoma sebaceum, mental deficiency, epilepsy
• adenoma sebaceum: symmetric yellow-red papules on cheek, nose, and forehead. Not associated w/ sebaceous gland (actually angiofibromas)
• Shagreen patch: connective tissue nevus (excess collagen)
• Koenen’s tumor: small periungal (near nail) fibromas
• Hypomelanotic macules
• CNS, kidneys, cardiac, and pulmonary systems affected

Question 9

Marfan’s syndrome

Answer 9

• Autosomal dominant, deficiency of fibrillin (microfibril sheath around elastin in dermis)
• Involves skin, eyes, MSK, CV (aortic aneurysm)
• Cutaneous features: stretch marks (striae), elastosis perforans serpiginosa (elastic connective tissue come off)
• Disproportionate extremities size w/ body size

Question 10

Dystrophic epidermolysis bullosa

Answer 10

• Severe supepidermal blisters, both recessive and dominant types
• Defect of col type 7 (component of anchoring fibrils)
• Epidermis is not attached to dermis (extremely fragile skin)
• Severe scars with milia, “mitten deformity” (scarring replaces fingers)
• Also involves mucosa (esophagus)
• Increased risk of SCC

Question 11

Ehlers-Danlos syndrome

Answer 11

• Connective tissue disorders
• Excessively stretching and fragility of the skin
• Have hyper flexible joint, atrophic scaring (fish mouth appearance)
• Gorlin’s sign: can touch tongue to nose
• Mulluscoid pseudotumors
• Mitten deformity, SCC risk

Question 12

Fabry’s disease

Answer 12

• X-linked recessive, heterozygous females have variable expression, lysosomal storage disease
• Deficiency in galactosidase A
• Accumulation of globotriacylceramide (glycolipid) in vascular endothelium, vascular smooth muscle, arrector pili, myocardium, corneal epithelia, others
• Produce angiokeratomas: symmetrical growths btwn umbilicus and knees, on oral mucosa, conjunctiva
• Can have hypo/anhidrosis (reduced sweating-> over heating)
• PNS, CV, kidney, CNS, eyes, and ears also are affected