Genetics of Endocrinology Flashcards
what is a monogenic disorder
single gene aetiology
what are the patterns of inheritance of a monogenic disorder
AD, AR, XLD, XLR, Y-linked, mitochondrial
what are polygenic disorders
caused by multiple genes often with environmental influences
what pattern of monogenic inheritance means males can only pass it on to females
x linked dominant
what pattern of monogenic inheritance means females are carriers, males get affected
X linked recessive
what pattern of monogenic inheritance means only males are affected
Y linked
what pattern of monogenic inheritance means you inherit from mother
mitochondrial (always get mitochondrian DNA from mum)
name 3 monogenic endocrine tumour syndromes
MEN 1, MEN 2, von hippel-lindau disease
what gene causes MEN 1 syndrome
MEN 1, 11 q
what gene causes MEN 1 syndrome
REY
what gene causes von hippel lindau syndrome
VHL
what tumours associated with MEN 1
pituitary, parathryoid, pancreatic + loads more
what tumours are associated with MEN 2
thyroid medullary (C cell), adrenal chromaffin (pheochromocytoma), parathyroid hyperplasia
what pattern of inheritance does MEN 1 and 2 follow
autosomal dominant
what is the MEN 1 gene
a tumour suppressor
what is the RET gene
proto-oncogene
what do MEN 1 mutations cause
loss/ reduced protein function
what do RET mutations cause
activate activation of tyrosine kinase
why is MEN 1 so important
premature morbidity and mortality (50%)
considerable psychological burden
dealing with incertainty
what are the leading causes of death in MEN 1
malignant pancreatic neuroendocrine tumour
thymic carcinoids
what does mutation analysis of
MEN 1 allow
Identification of ‘at risk’ individuals
Contact tracing of additional family members
Reassurance to those without the familial MEN1 mutation
Periodic screening and early tumour detection in those at risk
Appropriate genetic counselling
what is the treatment for MEN 2
Medullary Thyroid Cancer
-Prophylactic thyroidectomy
Screening for Pheochromocytoma
screening for parathyroid disease
where is the mutation in carney complex
protein kinase PKA
what are the clinical features of carney complex
PPNAD (adrenal glands make excess cortisol - cushings)
acromegaly (GH producing adenoma)
thyroids carcinoma
what are the features of mccune albright syndrome
Café-au-lait skin pigmentation
Precocious puberty (typically females)
Thyroid nodules
Pituitary – GH excess
Cushing’s syndrome (adrenal)
what is the inheritance of von hippel lindau
autosomal dominant
what does von hippel lindau cause
range of vascular tumours
what are the features of neurofibromatosis
Axillary freckling Café-au-lait patches Neurofibromas Optic gliomas Scoliosis (learning difficulties in some)
Phaeochromocytoma (rare)- secrete
high levels od adrenaline/ noradrenaline
which can cause hypertension
where is the mutation in neurofibromatosis type 1
NF1 gene
what are SDH B, C and D
Key mitochondial enzymes involved in succinate metabolism and Kreb’s cycle
describe SDHD
causes head and neck paragangliomas
get it from Dad
decscribe SDHB
causes malignant paragangliomas
B for Bad
