endocrine genetics Flashcards
monogenic disorders
single gene aetiology 6 modes of inheritance: - autosomal dominant - autosomal recessive - x linked recessive - x linked dominant - Y inheritance - mitochondrial inheritance
polygenic disorders
multi-gene aetiology which often have environmental influences
the classic monogenic endocrine tumours that will come up in exams
- MEN 1
- MEN 2A
- MEN 2B
- CARNEY COMPLEX
- MCCUNE- ALBRIGHT SYNDROME
- VON- HIPPEL LINDAU DISEASE
- NEUROFIBROMATOSIS TYPE 1
MEN 1 is inherited
autosomal dominantly
3 classic tumours occurring in MEN
- Pituitary adenoma
- Parathyroid hyperplasia
- Pancreatic islet cell tumour
men 1 is suspected if someone has
2/3 or more of the classic tumours
men 1 is caused by a mutation on the
men 1 gene on 11q13.1 on chromosome 11
pathophysiology of men 1
men 1 gene codes for a protein called menin which is a tumour suppressor gene
men 1 is also known as
warmer syndrome
types of pancreatic tumours that occur in men 1
- insulomas cause excessive insulin secretion causing hypoglycaemia
- gastrinomas cause excessive gastrin secretion causing petit ulcers
- VIPomas cause excesssive vasoactive intestinal peptide secretion causing severe diarrhoea
gastronome is also known as
zollinger ellison syndrome
is there a genotype phenotype correlation in men 1
no you cannot predict which tumours will occur
men 1 tumours are
mostly benign but 50% of those affected die from the disease
pituitary tumours that occur in MEN 1
- most commonly is a proclatinoma causing hyperprolactinaemia
- also can be a growth hormone secreting adenoma causing acropmgealy in adults and gigantism in children
what causes death in people with men 1
- malignant pancreatic neuroendocrine tumour
- thymic carcinoid
monitoring of people with men 1
- prolactin and growth hormone levels
- calcium and parathyroid levels
- gastrin levels
- MRI
MEN 2 is inherited
autosomal dominantly
men 2 is caused by a mutation on
the RET gene on chromosome 10q11.2 which codes for the RET protein which is a photo-oncogene
ret mutation affects
specific cysteine residues most commonly the C634 CODON
RET MUTATION REUSLTS IN
activation of receptor tyrosine kinase A
is there a genotype phenotype correlation in men 2
yes a very strong one, depends on the mutation you can predict which tumours will occur
MEN2A
- parathyroid hyperplasia
- medullary thyroid carcinoma
- pheochromocytoma
men 2a also known as
sipple syndrome
MEN2B
- mucosal neuromas
- medially thyroid carcinoma
- pheochromocytoma
- marfanoid body habitus (same body shape as marfans disease)
management of MEN 2
prophylactic thyroidectomy at the earliest age possible, screen for pheochromocytoma if high risk screen from age 11 if moderate risk screen from age 16
Carney complex is inherited
autosomal dominantly
carney complex is caused by a mutation in
PRKAR1A GENE
PRAKAR1A provides instruction
for making one subunit go the enzyme protein kinase A this leads to excessive protein kinase A signalling causing uncontrolled cell proliferation
classic presentation of carney complex
- primary pigmented nodular adrenocortial disease (ACTH independent autonomous hyper secretion of cortisol causing cushings syndrome)
- cardiac myxoma
- acromegaly due to pituitary adenoma
- thyroid carcinoma
mccune- albright syndrome is inherited
IT IS NOT INHERITED AND OCCURS SPORADICALLY
mccune albright syndrome occur due to a mutation in
GNAS gene which code for G proteins causing excessive cAMP signalling
presentation of mccune albright syndrome
- cafe au last skin (coast of main appearance)
- polyostotic fibrous dysplasia ( scar like fibrous tissue in the bones)
- early puberty in females
- thyroid nodules
- pituitary adenoma
- cushings syndrome
von hippel lindau syndrome is inherited
autosomal dominant
von hippel lindau syndrome is caused by a mutation in
the VHL gene which is a tumour suppressor gene causing abnormal cell proliferation
presentation of von hippel lindau syndrome
- CNS haemangioblastomas
- retinal haemangiobalstomas
- endolymphatic sac tumours of the middle ear
- pheochromocytoma and clear cell renal carcinoma
- pancreatic cysts, serous cyst adenomas, tumours
- epididymal (male) or broad ligament (females) cystadenomas
neurofibromatosis type 1 is caused by
autosomal dominant inheritance
neurofibromatosis type 1 is caused by
mutation in NF1 gene on chromosome 17q11.2
presentation of neurofibromatosis type 1
- axillary and inguinal freckling
- cafe au lait manuels
- lisch nodules
- optic gliomas
- scoliosis
- rarely phaeochromocytomas
hereditary peraganglia phaeochromocytoma
- autosomal dominant inheritance
- benign tumour of the pre ganglia of the adrenal gland resulting in overproduction of adrenaline and noradrenaline
- caused by mutation in SDHD GENE
