Genetic Diseases Woot!

1. Genetic Diseases Woot!

2. Adult Polycystic Kidney Disease • Sx: • Path: • Mutation? • Associated with: • Inheritance? • Juvenile polycystic kidney disease is AR! • Pain, hematuria, HTN, renal fail. • Bilaterally large, cystic kidneys • 90% APKD 1 (Chromosome 16) • Polycystic liver disease, BERRY ANEURYSMS, MVP. • Autosomal Dominant

3. Familial Hypercholesterolemia • Sx: • Inheritance? • Elevated LDL due to decreased LDL recep. Hetero: 300, Homo: 700 • Severe atherosclerosis early. • Tendon xanthomas (achilles) • Autosomal Dominant • AKA: hyperlipidemia type IIA

4. Marfan Syndrome • Sx: • Inheritance? • Mutation? • Skeletal abn: tall, long extremities, pectusexcavatum, hyperextensive joints, long fingers/toes (arachnodactyly) • CV: aortic cystic medial necrosis may lead to dissecting aneurysm. Floppy mitral valve. • Eyes: subluxation of lens. • Autosomal Dominant • Fibrillin gene

5. Neurofibromatosis Type 1 • AKA: • Sx: • Inheritance? • Mutation? • Von Recklinghausen’s Disease • Café au lait spots, neural tumors, Lisch nodules (iris hamartomas) • Skeletal: scoliosis • Optic pathway gliomas, pheos, increased tumors. • Autosomal Dominant • Chromosome 17

6. Tuberous Sclerosis • Sx: • Inheritance? • Mutation? • Facial lesions (adenoma sebaceum), • hypopigmented ask leaf spots • cortical/retinal hamartomas • Sz/mr • Renal cysts and angiomyolipomas. • Cardiac rhabdomyomas • Increased astrocytomas • Autosomal Dominant • Incomplete penetrance and variable presentation!

7. Neurofibromatosis Type 2 • Sx: • Inheritance? • Mutation? • Bilat acoustic neuroma, juvenile cataracts • Autosomal Dominant • NF2 gene on Chromosome 22

8. Von Hippel-Lindau Disease • Sx: • Inheritance? • Mutation? • Hemangioblastomas, renal cell carcinomas, • Autosomal Dominant • VHL gene (tumor supressor) on chromosome 3p. • VHL = 3.

9. Huntington’s Disease • Sx: • Inheritance? • Mutation? • Depression • dementia • Choreiform movements • Caudate atrophy • Decreased GABA/ACH levels • Sx btw 20-50 yrs. • Autosomal Dominant • Chromosome 4. • Triplet repeat disorder

10. Familial Adenomatous Polyposis • Sx: • Inheritance? • Mutation? • colon overtaken by adenomatous polyps, total colectomy necessary. • Autosomal Dominant • APC gene on chromosome 5

11. Hereditary Spherocytosis • Sx: • Inheritance? • Spheroid RBCs hemolytic anemia • Autosomal Dominant • Splenectomy cure

12. Achondroplasia • Pathogenesis • Sx: • Inheritance? • Signaling defect of fibroblast growth factor recep 3. • Dwarfism, short limbs with regular head and trunk. • Autosomal Dominant • ? Advanced Paternal age plays a role?

13. Cystic Fibrosis • Inheritance? • Mutation? • Pathophys? • Sx? • Dx? • Tx? • Autosomal Recessive • CTFR channel mutation on chromosome 7, deletion of Phe508. • Normally secretes Cl- in lungs/GI, reabsorbs from sweat. • Defect = abnormally thick mucus that plugs airways, pancreatic duct and liver probs. • Chronic bronchitis, bronchiectasis, pancreatic insufficiency (malabsorption and steatorrhea), meconium ileus in babies. Male infertility due to lack of vas deferens. Fat sol vitamin defs common. • Sweat test measuring Cl- concentration • N-acetyl-cysteine (mucolytic) • MOST COMMON LETHAL GENETIC DISEASE IN CAUCASIANS!

14. Glycogen storage diseases • Alpha 1 antitrypsin • Hereditary spherocytosis • PKU • Thalassemias • Mucopolysaccharidoses • Hunter’s • CF • Hurler’s • Sphingolipidoses • Fabry’s Disease • Albinism • Infant polycystic kidney dz • Adult polycystic kidney dz • Hemochromatosis • Sickle cell anemia • Familial adenomatouspolyposis • Achondroplasia • Huntington’s • Von HippelLindaus • AR • Codominant • AD • AR • AR • Mostly AR (which one no?) • Only MPS that is X-linked R • AR • AR • Mostly AR (which one no?) • Only sphingolipidosis that is X-linked R • AR • AR • AD • AR • AR • AD • AD • AD • AD