Repro 15 - Genetic Disorders: AD And Trinucleotide Repeats Flashcards
What are the features of Autosomal Dominant Polycystic Kidney Disease? What is the cause?
Multiple large cysts not only in kidneys but possible in liver, pancreas, brain and arterial blood vessels. Always bilateral. Presents w/ flank pain, hematuria, hypertension, progressive renal failure. Due to APKD1 on chromosome 16. Associated w/ Berry aneurysms.
What is Achondroplasia? What is the cause?
Dwarfism. Due to FGF receptor 3 being turned on. Associated w/ advanced paternal age. Autosomal Dominant, more of a sporadic mutation.
What is Familial Adenomatous Polyposis? What is the cause?
Colon covered w/ polyps after puberty. Progresses to colon cancer unless those polyps are removed. Due to mutation of APC gene. Autosomal Dominant.
What is Gardner’s syndrome? What is the cause of it?
Autosomal dom. Causes polyps in the colon and tumors outside the colon. Osteomas, lipomas, sebaceous cysts, colon polyps, colon cancer. Caused by mutation of the APC gene.
What is Familial Hypercholesterolemia? What is the cause of it?
Type IIA hyperlipidemia. Huge LDL. Caused by defective or absent LDL receptor. Heterozygotes have LDL above 300. Homozygotes have LDLs over 700.
What is Hereditary Hemorrhagic Telangiectasia?
Osler-Weber Rend syndrome. Causes Abnormal blood vessel formation: skin, mucous membranes, organs. This causes telangiectasia, recurrent epistaxis, Skin discoloration, Arteriovenous malformation (AVMs), Chronic GI tract bleeding.
What is Hereditary Spherocytosis and what is the cause?
Autosomal Dom. Defect in structural framework for RBCs caused by Spectrin defect or ankyrin defect. This causes round-shaped RBCs, increasing blood viscosity, more prone to hemolysis (hemolytic anemia and jaundice). Worsens w/ viral infections. MCHC is elevated: due to membrane loss and red cell dehydration.
What is MCHC?
Mean cell hemoglobin concentration, measures the concentration of hemoglobin in a given volume of RBCs.
How do we diagnose Hereditary Spherocytosis? How do we treat it?
Dx: Hemolytic anemia, Spherocytes, abnormal osmotic fragility test. Tx: splenectomy.
What are the finding of Huntington’s disease in MRI?
Atrophy of caudate nucleus. Enlarged lateral ventricles. Defined sulci. Atrophy of putamen.
What is Huntington’s disease?
Autosomal Dom. The 7 C’s of Huntington disease: CAG repeat. Cognitive decline. Caudate atrophy. Chorea. Chromosome “Cuatro”. Cuarenta. acetylCholine decrease. It also causes Depression, decreased level of GABA and acetylcholine in the brain.
What is Marfan syndrome and what is the cause of it?
Autosomal Dom, a connective tissue disorder. They are tall, pectus excavatum, long extremities, hyperextendible joints. Due to fibrillin gene mutation. Can also cause cystic medial necrosis of the aorta, causing aortic regurgitation, aortic aneurysm, aortic dissection. Floppy mitral valve that can lead to MVP. Subluxation of the lenses.
What gene is associated w/ MEN1?
MEN1 gene.
What gene is associated w/ MEN2A and MEN2B?
RET gene.
What is MEN?
Autosomal dom. Multiple endocrine Neoplasia. Causes tumors of hormone producing glands.
What are the symptoms of MEN1?
The 3 P’s. Pituitary adenomas. Parathyroid adenomas. Pancreatic tumors.
What are the symptoms of MEN2A?
[MPP] Medullary thyroid carcinoma. Parathyroid adenomas. Pheochromocytoma.
What are the symptoms of MEN2B?
[MMP] Medullary thyroid carcinoma. Mucosal tumors. Pheochromocytoma.
What is Neurofibromatosis Type 1 and what is the cause?
AKA von Recklinghausen’s disease. Autosom dom. Caused by mutation of a gene on chrom 17 that is responsible for control of cell division. Cafe-aulet spots, neural tumors, Lysch nodules (pigmented iris hamartomas), scoliosis.
What type of Neurofibromatosis is associated w/ bilateral acoustic neuromas?
Neurofibromatosis type 2.
What is Neurofibromatosis type 2 and what is the cause?
Hearing loss, tinnitus, balance problems. Cataracts and other neurologic tumors and cutaneous manifestations. Bilateral Caused by mutation on chromosome 22. [On chromosome 2, causes two-ning problems, two sides]
What is Tuberous Sclerosis? What is the cause?
Non-malignant tumors in the brain and other organs. Facial lesions (adenoma sebacium). Hypopigmented ashleaf spots on skin. Cortical and retinal hamartomas, causing seizures. Causes intellectual disability. Associated with cardiac rhabdomyomas and astrocytomas. Caused by Mutated hamartin (or tuberin) gene. It has imcomplete penetrance and variable presentation.
What is von Hippel-Lindau disease? What is the cause?
An autosomal dom. Causes multiple types of tumors: Hemangioblastomas in retina, cerebellum, medulla. Half of patients develop multiple bilateral renal cell carcinomas. Pheochromocytomas. Associated w/ deletion of the VHL gene, resulting in constant expression of HIF, a transcription factor, which causes activation of angiogenic growth factors, causing the hemangioblastomas.
What are the 4 important trinucleotide repeat diseases?
[Hunting for My Fried X] Huntington (CAG). Myotonic dystrophy (CTG). Friedreich ataxia (GAA). Fragile X syndrome (CGG).
