Autosomal dominant diseases

Question 1

ADPKD

Answer 1

Bilateral, massive enlargement of kidneys due to multiple large cysts, mutation in PKD1 and PKD2

Question 2

Familial adenomatous polyposis

Answer 2

Colon becomes covered with adenomatous polyps after puberty. Progresses to coon cancer unless colon is resected

Mutations on chromosome 5q (APC gene)

Question 3

Familial hypercholesterolemia

Answer 3

Elevated LDL due to defective or absent LDL receptor

Leads to severe atherosclerotic disease in life, corneal arcus, tendon xanthomas (classically Achilles tendon)

Question 4

Hereditary hemorrhagic telangiectasia

Answer 4

Inherited disorder of blood vessels

Branching skin lesions (telangiectasias), recurrent epistaxis, skin discolorations, AV malformations, GI bleeding, hematuria

Osler-Weber-Rendu syndrome

Question 5

Hereditary spherocytosis

Answer 5

Spheroid erythrocytes due to spectrin or ankyrin defect; hemolytic anemia; increase in MCHC and RDW

Tx: splenectomy

Question 6

Huntington disease

Answer 6

Findingsg: depression, progressive dementia, choreiform movements, caudate atrophy
Increased DA, decreased GABA, decreased ACh in the brain. Gene on chromosome 4; trinucleotide repeat disorder: (CAG)n

Demonstrates anticipation

Question 7

Li-Fraumeni syndrome

Answer 7

Abnormalities in TP53, multiple malignancies at an early age. Also known as SBLA cancer syndrome (sarcoma, breast, leukemia, adrenal gland)

Question 8

Marfan snydrome

Answer 8

FBN1 gene mutation on chromosome 15
Defective fibrillin (scaffold for elastin) -> connective tissue disorder affecting skeleton, heart, and eyes.
Tall with long extremities, pectus excavatum, hypermobile joints, and long, tapering fingers and toes. Cystic medial necrosis of aorta, incompetence and dissecting aortic aneurysms; floppy mitral valve. Subluxation of lenses

Question 9

MEN

Answer 9

1, 2A, 2B
Familial tumors of endocrine glands, including those of the pancreas, parathyroid, pituitary, thyroid, adrenal medulla. MEN 1 = MEN1 gene
2A and 2B: RET gene

Question 10

Neurofibromatosis type 1 (von Recklinghausen)

Answer 10

Neurocutaneous disorder characterized by cafe-au-lait spots, cutaneous neurofibromas, optic gliomas, pheochromocytomas, Lisch nodules.

100% penetrance, variable expression, NF1 gene on chromosome 17

Question 11

Neurofibromatosis type 2

Answer 11

Bilateral acoustic schwannomas, juvenile cataracts, meningiomas, ependymoms, gliomas, neurofibromas

NF2 gene on chromosome 22

Question 12

Tuberous sclerosis

Answer 12

Neurocutaneous disorder with multi-organ system involvement, characterized by numerous benign hamartomas. Near-complete penetrance ,variable expression
Ash-leaf spots, intellectual disability, seizures, facial angiofibromas, astrocytomas

Question 13

von Hippel-Lindau disease

Answer 13

Development of numerous tumors, both benign and malignant. Associated with deletion of VHL gene (tumor suppressor)on chromosome 3 (3p)