Autosomal Dominant Diseases Flashcards
Autosomal dominant polycystic kidney disease is also known as
Adult polycystic kidney disease
Autosomal dominant disease are often
PLEIOTROPIC
Autosomal dominant polycystic kidney disease is due to
- PKD1 on ch 16 (85%)
2. PKD2 on ch 4 (15%)
Autosomal dominant polycystic kidney disease is bilateral or unilateral / morphology
Always bilateral
Massive enlargement of kidneys due to multiple large cysts
Familial adenomatous polyposis(FAP) morphology
Colon becomes covered with adenomatous polyps after puberty
Familial adenomatous polyposis age of appearance
After puberty
Familial adenomatous polyposis is due to
APC gene (ch5) mutation
Chromosome of APC
5
Familial hypercholesterolemia pathophysiology
Elevated LDL due to defective or absent LDL receptor
Familial hypercholesterolemia leads to:
- Severe atherosclerotic disease early in life
2. Tendon xanthomas (classically in the Achilles tendon)
Hereditary spherocytosis is due to
Spectrin or ankyrin defect
Hereditary hemorrhagic telengiectasia is also known as
Olser - Weber - Rednu
Hereditary spherocytosis main finding
Hemolytic anemia with increased MCHC and increased RDW
What is hereditary hemorrhagic telangiectasia
Inherited (AD) disorder of blood vessels
Tuberous sclerosis
Neurocutaneous disorder with multi-organ system involvement, characterized by numerous bening HAMARTOMAS
Finding of hereditary hemorrhagic telangiectasia
- branching skin lesions (Telangiectasia) 2. Recurrent epistaxis 3. Skin discoloration 4. Arteriovenous malformations 5. GI bleeding 6. Hematuria
Tuberous sclerosis phenotype expression features
Incomplete penetrance and variable expression
Von hippel-lindau is characterized by development of
Numerous tumors (both benign and malignant)
Von Hippel-Lindau disease pathophysiology (genes)
Deletion of VHL gene (tumor suppressor - ch 3)
Huntington symptoms / morphology
- Depression
- Progressive dementia
- Choreiform movments
- aggression
morphology: caudate atrophy
NF2 findings
- Bilateral acoustic schwannomas
- Juvenile cataracts
- Meningiomas
- Ependymomas
Huntington lab findings
Low levels of GABA and ACH
high levels of dopamine
NF2 chromosome
22
NF1 - AKA
Von Recklinghausen disease
Neurofibromatosis type 1 (von Recklinghausen disease) inheritance features
100% penetrance
Variable expression
Neurofibromatosis type 1 (von Recklinghausen disease) - presentation
- cafe-au-lait spots
- cutaneous neurofibromas
- optic glioma
- pheochromocytomas
- Lisch nodules (pigmented iris hamartomas)
Neurofibromatosis type 1 (von Recklinghausen disease) is caused by
Mutations in NF1 gene in ch 17
Marfan syndrome - comective tissue disorder affecting:
Skeleton, heart, eyes
Cardiovascular/ marfan
- Floppy mitral valve
2. Dissecting aortic aneurysm (cystic medial necrosis of aorta)
Marfnan pathophysiology
Fibrillin 1 gene mutation (FBN1) ON CHROMOSOME 15 –> defective fibrillin (scaffold for elastin) –> connective tissue disorder
Marfan eyes
Subluxation of lenses, typically upward and temporally
Marfan skeleton
- Tall with long extremities
- Pectus excavactum
- Hypermobile joints
- Long tapering fingers and toes (arachnodactyly)
APC ch
5
NF1 ch
17
NF2 ch
22
VHL ch
3
Huntington chromosome
Repeated trinucleotide disorder
4 CAG
Marfan gene and chromosome
FBN1 gene on ch15
Li-Fraumeni syndrome - mechanism
Abnormalities in TP53 –> multiple malignanciesin TP53
Li-Fraumeni syndrome - presentation
multiple malignanciesin TP53 –> AKA SBLA –> sarcoma, breast, leukemia, adrenal gland
