Autosomal Dominant Diseases

Question 1

Autosomal Dominant Polycystic Kidney Disease

Answer 1

Bilateral, massive enlargment of kidneys due to multiple large cysts; Due to mutations in PKD1 (chr. 16) or PKD2 (chr. 4)

Question 2

Familial Adenomatous Polyposis

Answer 2

Mutations in APC gene on chr. 5q

Question 3

Hereditary Hemorrhagic Telangiectasia

Answer 3

Inherited disorder of blood vessels
Findings: branching skin lesions (telangiectasias), recurrent epistaxis, skin discolorations, arteriovenous malformations, GI bleeding, hematuria

Question 4

Hereditary Spherocytosis

Answer 4

Spheroid erythrocytes due to spectrin or ankyrin defect; hemolytic anemia; increased MCHC, increased RDW
Tx: splenectomy

Question 5

Li-Fraumeni Syndrome

Answer 5

Abnormalities in TP53 –> multiple malignancies at an early age; Sarcoma, breast, leukemia, adrenal gland

Question 6

Marfan Syndrome

Answer 6

FBN1 gene mutation (chr. 15) –> defective fibrin (scaffold for elastin) –> connective disorder affecting skeleton, heart, and eyes
Findings: tall with long extremities, pectus excavatum, hypermobile joints and long, tapering fingers and toes (archnodactyly); Cystic medial necrosis of aorta –> aortic incompetence and dissecting aneurysms; Floppy mitral valves; Subluxation of lenses, typically upward and temporally

Question 7

NF1

Answer 7

Neurocutaneous disorder characterized by cafe-au-lait spots, cutaneous neurofibromas, optic gliomas, pheochromocytomas, Lisch nodules (pigmented iris hamartomas)
NF1 gene chr. 17

Question 8

NF2

Answer 8

Bilateral acoustic schwannomas, juvenile cataracts, meningiomas and ependymomas; NF2 gene on chr. 22

Question 9

Tuberous Sclerosis

Answer 9

Numerous benign hamartomas; Incomplete penetrance, variable expression