Principles: Genetics Flashcards
The inheritance of hypophosphatemic rickets is…
X-linked Dominant.
Increased phosphate wasting at the proximal tubule. Rickets-like presentation.
Mothers transmit to 50% of all daughters and sons.
Fathers transmit to 100% of all daughters but no sons.
What type of inheritance presents with “ragged red fibers” on muscl;e biopsy?
Mitochondrial myopathies - myopathy, lactic acidosis, CNS disease secondary to failure in oxidate phosphorylation. Transmited only through the mother.
How does autosomal dominant polycystic kidney disease present?
What chromosome is the defect on?
Bilateral massive enlargement of the kidneys due to multiple large cysts that presents in adulthood.
85% due to PKD1 (chromosome 16, 16 letters in “polycystic kidney”)
Remainder due to mutation in PKD2 (chromosome 4)
How does familial adenomatous polyposis present?
What chromosome?
Colon covered with adenomatous polyps after puberty. Will progress to cancer unless resected.
Mutations on chromosome 5 (APC gene, 5 letters in “polyp”.)
Autosomal Dominant
What is defective in familial hypercholesterolemia?
What is the classic presentation?
Elevated LDL due to defective or absent LDL receptor.
Leads to atherosclerotic disease early in life and tendon xanthomas (classically in the Achilles tendon).
Autosomal Dominant
What is the presentation of hereditary hemorrhagic telangiectasia?
Inherited (autosomal dominant) disorder of blood vessels.
Telangiectasia, epistaxis, skin discolorations, arteriovenous malformations, GI bleeding, hematuria.
AKA Osler-Weber-Rendu syndrome.
What is the issue in Hereditary spherocytosis?
Treatment?
Spheroid erythrocytes due to autosomal dominant spectrin or ankyrin defect; hemolytic anemia.
High MCHC
Treatment: Splenectomy
What is characteristic of Huntington disease?
Where is the genetic defect?
Depression, dementia, choreiform movements, caudate atrophy, decreased levels of GABA and ACh in the brain.
Gene on chromosome 4; trinucleotide repeat disorder (CAG)n.
Increased repeats, reduced age of onset. “Hunting 4 food”.
Autosomal dominant.
What is the gene mutation in Marfan syndrome?
What are some symptoms?
Fibrillin-1 gene mutation, autosomal dominant.
Tall with long extremities, pectus excavatum, hypermobile joints, long tapering fingers and toes (arachnodactyly); cystic medial necrosis of aorta -> aortic incompetence and dissecting aortic aneurysms, floppy mitral valve.
Subluxation of lenses, upward and temporally.
What is the inheritance pattern of MEN diseases?
Autosomal dominant.
How does neurofibromatosis type 1 present?
Where is the genetic defect?
Autosomal dominant, neurocutaneous.
Cafe-au-lait spots and cutaneous neurofibromas. 100% penetrance but variable expression.
Mutations in NF1 gene on chromosome 17. 17 letters in “von Recklinghausen”.
How does neurofibromatosis type 2 present?
Where is the genetic defect?
Bilateral acoustic schwannomas, juvenile cataracts, meningiomas, ependymomas.
Autosomal dominant.
NF2 gene on chromosome 22; type 2 = 22.
How does tuberous sclerosis?
What is its inheritance?
Neurocutaneous disorder with multi-organ system involvement, characterized by numerous benign hamartomas.
Incomplete penetrance, variable expression. Autosomal dominant.
What are symptoms of von-Hippel-Lindau disease?
How is it inherited?
Disorder characterized by development of numerous tumors.
Associated with deletion of VHL gene (tumor suppressor) on chromosome 3. Autosomal dominant.
von-Hippel-Lindau - 3 words for chromosome 3.
What chromosome carries Prader-Willi syndrome and Angelman syndrome?
Where is the defect?
Mutation or deletion on chromosome 15 or uniparental disomy.
Prader-Willi: Paternal gene is deleted/mutated and maternal gene is normally silent. Hyperphagia, obesity, intellectual disability, and hypotonia.
AngelMan syndrome: Maternal gene is deleted/mutated and paternal gene is normally silent. Results in inappropriate laughter (“happy puppet”), seizures, ataxia, and severe intellectual disability.
