endocrine genetics

Question 1

monogenic disorders

Answer 1

single gene aetiology 
6 modes of inheritance: 
- autosomal dominant 
- autosomal recessive
- x linked recessive 
- x linked dominant 
- Y inheritance 
- mitochondrial inheritance

Question 2

polygenic disorders

Answer 2

multi-gene aetiology which often have environmental influences

Question 3

the classic monogenic endocrine tumours that will come up in exams

Answer 3

• MEN 1
• MEN 2A
• MEN 2B
• CARNEY COMPLEX
• MCCUNE- ALBRIGHT SYNDROME
• VON- HIPPEL LINDAU DISEASE
• NEUROFIBROMATOSIS TYPE 1

Question 4

MEN 1 is inherited

Answer 4

autosomal dominantly

Question 5

3 classic tumours occurring in MEN

Answer 5

• Pituitary adenoma
• Parathyroid hyperplasia
• Pancreatic islet cell tumour

Question 6

men 1 is suspected if someone has

Answer 6

2/3 or more of the classic tumours

Question 7

men 1 is caused by a mutation on the

Answer 7

men 1 gene on 11q13.1 on chromosome 11

Question 8

pathophysiology of men 1

Answer 8

men 1 gene codes for a protein called menin which is a tumour suppressor gene

Question 9

men 1 is also known as

Answer 9

warmer syndrome

Question 10

types of pancreatic tumours that occur in men 1

Answer 10

• 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

Question 11

gastronome is also known as

Answer 11

zollinger ellison syndrome

Question 12

is there a genotype phenotype correlation in men 1

Answer 12

no you cannot predict which tumours will occur

Question 13

men 1 tumours are

Answer 13

mostly benign but 50% of those affected die from the disease

Question 14

pituitary tumours that occur in MEN 1

Answer 14

• most commonly is a proclatinoma causing hyperprolactinaemia
• also can be a growth hormone secreting adenoma causing acropmgealy in adults and gigantism in children

Question 15

what causes death in people with men 1

Answer 15

• malignant pancreatic neuroendocrine tumour

- thymic carcinoid

Question 16

monitoring of people with men 1

Answer 16

• prolactin and growth hormone levels
• calcium and parathyroid levels
• gastrin levels
• MRI

Question 17

MEN 2 is inherited

Answer 17

autosomal dominantly

Question 18

men 2 is caused by a mutation on

Answer 18

the RET gene on chromosome 10q11.2 which codes for the RET protein which is a photo-oncogene

Question 19

ret mutation affects

Answer 19

specific cysteine residues most commonly the C634 CODON

Question 20

RET MUTATION REUSLTS IN

Answer 20

activation of receptor tyrosine kinase A

Question 21

is there a genotype phenotype correlation in men 2

Answer 21

yes a very strong one, depends on the mutation you can predict which tumours will occur

Question 22

MEN2A

Answer 22

• parathyroid hyperplasia
• medullary thyroid carcinoma
• pheochromocytoma

Question 23

men 2a also known as

Answer 23

sipple syndrome

Question 24

MEN2B

Answer 24

• mucosal neuromas
• medially thyroid carcinoma
• pheochromocytoma
• marfanoid body habitus (same body shape as marfans disease)

Question 25

management of MEN 2

Answer 25

prophylactic thyroidectomy at the earliest age possible, screen for pheochromocytoma if high risk screen from age 11 if moderate risk screen from age 16

Question 26

Carney complex is inherited

Answer 26

autosomal dominantly

Question 27

carney complex is caused by a mutation in

Answer 27

PRKAR1A GENE

Question 28

PRAKAR1A provides instruction

Answer 28

for making one subunit go the enzyme protein kinase A this leads to excessive protein kinase A signalling causing uncontrolled cell proliferation

Question 29

classic presentation of carney complex

Answer 29

- primary pigmented nodular adrenocortial disease (ACTH independent autonomous hyper secretion of cortisol causing cushings syndrome) - cardiac myxoma - acromegaly due to pituitary adenoma - thyroid carcinoma

Question 30

mccune- albright syndrome is inherited

Answer 30

IT IS NOT INHERITED AND OCCURS SPORADICALLY

Question 31

mccune albright syndrome occur due to a mutation in

Answer 31

GNAS gene which code for G proteins causing excessive cAMP signalling

Question 32

presentation of mccune albright syndrome

Answer 32

- 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

Question 33

von hippel lindau syndrome is inherited

Answer 33

autosomal dominant

Question 34

von hippel lindau syndrome is caused by a mutation in

Answer 34

the VHL gene which is a tumour suppressor gene causing abnormal cell proliferation

Question 35

presentation of von hippel lindau syndrome

Answer 35

- 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

Question 36

neurofibromatosis type 1 is caused by

Answer 36

autosomal dominant inheritance

Question 37

neurofibromatosis type 1 is caused by

Answer 37

mutation in NF1 gene on chromosome 17q11.2

Question 38

presentation of neurofibromatosis type 1

Answer 38

- axillary and inguinal freckling - cafe au lait manuels - lisch nodules - optic gliomas - scoliosis - rarely phaeochromocytomas

Question 39

hereditary peraganglia phaeochromocytoma

Answer 39

- 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