Autosomal Dominant Diseases

Question 1

Familial Adenomatous Polyposis

Answer 1

Autosomal Dominant

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

Mutations on chromosome 5q (APC gene)

Question 2

Familial Hypercholesterolemia

Answer 2

Autosomal Dominant

Elevated LDL due to defective or absent LDL receptor. Leads to severe atherosclerotic disease early in life, corneal arcus, tendon xanthomas (classically in achilles), xanthelasmas.

Question 3

Autosomal Dominant Polycystic Kidney Disease

Answer 3

Autosomal Dominant (I know its in the name but its just a reminder)

Bilateral, massive enlargement of kidneys due to multiple large cyts.

85% due to PKD1 mutation on chromosome 16, remaining due to PKD2 on chromosome 4

Question 4

Hereditary Hemorrhagic Telangectasia

Answer 4

Autosomal Dominant

Inherited disorder of blood vessels. Branching skin lesions (telangiectasias), recurrent epistaxis, skin discolorations, AVM, GI bleeding, hematuria. Also known as osler-weber-rendu syndrome.

Question 5

Hereditary Spherocytosis

Answer 5

Autosomal Dominant

Spheroid erythrocytes due to spectrin or ankryin defect; hemolytic anemia. Inc MCHC, Inc RDW. Tx splenectomy.

Question 6

Huntingtons Disease

Answer 6

Autosomal Dominant

Findings: Depression, progressive dementia, choreiform movements, caudate atrophy. Inc DA, Dec GABA, Dec ACh in brain.

Gene on chromosome 4, CAG trinucleotide repeat disorder. Demonstrates anticipation: inc repeats –> dec age of onset.

Question 7

Li-Fraumeni syndrome

Answer 7

Autosomal Dominant

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

Question 8

Marfan Syndrome

Answer 8

Autosomal Dominant

FBN1 gene mutation on chromosome 15 –> defective fibrillin scaffolding –> connective tissue disorder affecting skeleton, heart, eyes.

Findings: tall w/long extremeties, pectus excavatum, hypermobile joints, long tapering fingers and toes. Cystic medial necrosis of aorta –> aortic incompetence and dissecting aortic aneurysms. Floppy mitral valve, upward and temporal subluxation of lens.

Question 9

Multiple endocrine neoplasias (MEN)

Answer 9

Autosomal Dominant

MEN1 = men1 gene

MEN 2a and 2b = RET gene

Question 10

NF1 (von Recklinghousen)

Answer 10

Autosomal dominant, 100% penetrance with variable expression

Neurocutaneous disorder: cafe-au-lait spots, cutaneous neurofibromas, optic gliomas, pheochromocytomas, lisch nodules (pigmented iris hamartomas).

Mutations in NF1 gene on chromosome 17

Question 11

NF2

Answer 11

Autosomal dominant

Findings: bilateral acoustic schwannomas, juvenile cataracts, meningiomas, ependymomas.

NF2 gene on chromosome 22

Question 12

Tuberous Sclerosis

Answer 12

Autosomal Dominant, incomplete penetrance, variable expression

pnemonic is HAMARTOMAS, look in neuro section for it

Question 13

VHL disease

Answer 13

Autosomal dominant

VHL gene, chromosome 3

Numerous tumors both benign and malignant, Common cause of renal cell carcinoma.