Genetics Flashcards
6 categories of monogenic inheritance?
Autosomal dominant Autosomal recessive X-linked dominant X-linked recessive Y-linked Mitochondrial
Describe a pattern of mitochondrial inheritance?
Mother affected and every child is also affected as it is the mother who passes on mitochondrial DNA.
4 reasons you would do genetic testing?
- Childhood/ early onset of disease
- Severe clinical phenotype out with normal
- Family history of relevant disease
- Clinical features consistent with genetic syndrome or associated with increased risk of germline mutation
Majority of monogenic diseases are caused by…
single nucleotide variants- missense, nonsense, splice site mutation
small insertions or deletions
Genetics of MEN type 1 vs type 2?
Type 1: Autosomal dominant disorder- loss of tumour suppressor gene, then lose functioning copy and get condition. Mutations can occur anywhere in the coding region so doesn’t help predict clinical manifestations.
Type 2: Autosomal dominant specific mutations in RET proto-oncogene resulting in activation of an oncogene. Where the mutation is will predict clinical manifestations and potential age of onset.
Describe what tumours MEN 1 are at risk of?
3Ps: More than 95% develop hyperparathyroisim and parathyroid tumours however the leading cause of death is malignant pancreatic neuroendocrine tumours. Pituitary tumours are also common. Lots of other manifestations.
Describe management of MEN 1?
Management of established tumours is same as treatment for similar tumours occurring sporadically. Serum calcium is a good screening test, in established cases need to screen via blood tests and imaging.
Describe what tumours MEN 2 are at risk of?
MEN 2A and B both get medullar thyroid cancer and pheochromocytoma. 2A also gets parathyroid tumours and 2B marfinoid habitus (syndrome resembling marfans), mucosal neuromas, medullated corneal fibres, intestinal autonomic ganglion dysfunction. MTC is usually first presentation.
Management of MEN 2?
Management of established tumours is same as treatment for similar tumours occurring sporadically. In those with high risk mutations prophylactic thyroidectomy should potentially be considered.
Genetics of neurofibromatosis type 1?
Autosomal dominant condition usually due to mutations in NF1
What are early signs of neurofibromatosis type 1?
Cafe au lait patches and axillary freckling
What are later signs of neurofibromatosis type 1?
Learning difficulties, skeletal dysplasia, fleshy skin tags, neurofibromas which can progress to cover the skin completely.
Although rare what endocrine disorders are associated with neurofibromatosis type 1?
Pheochromocytoma, acromegaly and Addisons disease
