Autosomal Dominant Diseases

Question 1

Achondroplasia

Answer 1

Cell-signaling defect of fibroblast growth factor (FGF) receptor 3. Results in dwarfism; short limbs, larger head, but trunk size normal. Associated with advanced PAternal age

Question 2

Autosomal-dominant polycystic kidney disease (APKD)

Answer 2

Massive enlargement of kidneys due to multiple cysts.
Presents w/ flank pain, hematuria, HTN, progressive renal failure.
85% due to mutation in PKD1- chromosome 16
Associated with polycystic liver disease, berry aneurysms, mitral valve prolapse.

Question 3

Familial adenomatous polyposis

Answer 3

Colon covered with adenomatous polyps after puberty.
Progresses to colon cancer unless colon resected.
Mutation on chromosome 5 - APC gene

Question 4

Familial hypercholesterolemia (hyperlipidemia type IIA)

Answer 4

Elevated LDL due to defective or absent LDL receptor.
Heterozygotes have LDL- 300mg/dL, Homozygotes 700- usually die early
Tendon xanthomas (classically in Achilles), MI before age 20

Question 5

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)

Answer 5

Disorder of blood vessels.

Telangiectasia, recurrent epistaxis, skin discolorations, arteriovenous malformations

Question 6

Hereditary spherocytosis

Answer 6

Spheroid erythrocytes due to spectrin or ankyrin defect.
Hemolytic anemia; increased MCHC
Splenectomy = curative

Question 7

Huntington’s disease

Answer 7

Trinucleotide repeat disorder (CAGCAG…) on chromosome 4.
Depression, progressive dementia, choreiform movements, caudate atrophy, and decreased GABA and ACh
Sx onset = 20-50yo

Question 8

Marfan’s syndrome

Answer 8

Fibrillin-1 gene mutation
Affects skeleton, heart, eyes= tall w/ long extremities, pectus excavatum, hypermobile joints, long, tapering fingers & toes (arachnodactyly)
Cystic medial necrosis of aorta= aortic incompetence = dissection
Floppy mitral valve, subluxation of lenses

Question 9

Multiple endocrine neoplasias

Answer 9

Familial tumors of endocrine glands

Only MEN 2A and 2B are associated with ret gene, NOT MEN1

Question 10

Neurofibromatosis type I (von Recklinghausen’s disease)

Answer 10

Gene mutation on chromosome 17
Café-au-lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas), scoliosis, optic pathway gliomas

“4 yo boy found to have several pigmented nodules on his irises and shows several light-brown macules on his trunk 1-3cm”

Question 11

Neurofibromatosis type 2

Answer 11

NF2 gene mutation on chromosome 22

Bilateral acoustic schwannomas, juvenile cataracts

Question 12

Tuberous sclerosis

Answer 12

Mutations of TSC1 (chromosome 9) and TSC2 (chromosome 16).
Affects cell functions early in development.
Facial lesions (adenoma sebaceum), hypopigmented "ash leaf spots" on skin
cortical and retinal hamartomas, seizures, mental retardation, renal cysts, and renal angiomyolipomas, cardiac rhabdomyomas, increased incidence of astrocytomas.
Incomplete penetrance, variable expression

Question 13

von Hippel-Lindau diease

Answer 13

Deletion of VHL gene (tumor suppressor) on chromosome 3 = constitutive expression of HIF (transcription factor) that activates angiogenic growth factors
Hemangioblastomas of retina/cerebellum/medulla
Multiple bilateral renal cell carcinomas

Question 14

Myotonic dystrophy

Answer 14

Trinucleotide repeats on myotonia-protein kinase gene
Sustained muscle contraction with weakness and atrophy
Cataracts, frontal balding, and gonadal hypertrophy