Genetics - AD diseases

Cell-signaling defect of FGF-R 3. Results in dwarfism; short limbs, but head and trunk are normal size. Assoc. with advanced paternal age

ALWAYS bilateral. massive enlargement of kidneys d/t multiple large cysts. Patients present with flank pain, hematuria, HTN, progressive kidney failure. 90% d/t APKD1 gene mutation on chromosome 16.
Assoc. with berry aneurysm, polycystic liver disease, MVP.

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

Elevated LDL d/t defective or absent LDL receptor. Heterozygous ~300 mg/dL; homozygous rare ~700 mg/dL; severe atherosclerotic disease early in life, tendon xanthomas (classically in Achilles tendon), MI may develop before 20

Inherited disorder of blood vessels.
Findings: telangiectasia, recurrent epistaxis, skin discoloration, AVM

d/t spectin, ankyrin defect; amolytic anemia, inc. MCHC. splenectomy curative

Findings: depression, progressive dementia, choreiform mvts, caudate atrophy, dec. levels GABA and ACh. Usu. btwn 20-50. Chromosome 4, CAG repeats

Fibrillin gene mutatin --> connective tissue disorder affecting skeleton, heart and eyes.
Findings: tall with long extremities, pectus excavatum, hyperextensive joints, long tapering fingers and toes (arachnodactyly), cytic medial necrosis of aorta --> aortic incompetence and dissecting aortic aneurysms, floppy mitral valve. Sublaxation of lenses, HF, scoliosis, bacterial endocarditis.

Type 2A, 2B assoc with ret gene

Findings: cafe-au-lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas), skeletal disorders (e.g. scoliosis), optic pathway gliomas.
Long arm of Chromosome 17

bilateral acoustic neuromas/schwannomas, juvenile cataracts,
chromosome 22

Findings: facial lesions (adenoma sebaceum), hypopigmented "ash leaf spots" on skin, cortical and retinal hamartomas, seizures, mental retardation, renal cysts, renal angiomyolipomas, cardiac rabdomyomas, inc. incidence of astrocytomas.
Incomplete penetrance, variable presentation

Findings: hemagioblastomas of retinal/cerebelllum/medulla, about 1/2 of affected pts develop multiple bilateral renal cell carcinomas and other tumors.
Assoc. with deleted of VHL gene (tumor suppressor) on chromosome 3p. Results in constitutive expression of HIF (transcription factor) and activation of angiogenic growth factors.