Genetics of Endocrinology

Question 1

what is a monogenic disorder

Answer 1

single gene aetiology

Question 2

what are the patterns of inheritance of a monogenic disorder

Answer 2

AD, AR, XLD, XLR, Y-linked, mitochondrial

Question 3

what are polygenic disorders

Answer 3

caused by multiple genes often with environmental influences

Question 4

what pattern of monogenic inheritance means males can only pass it on to females

Answer 4

x linked dominant

Question 5

what pattern of monogenic inheritance means females are carriers, males get affected

Answer 5

X linked recessive

Question 6

what pattern of monogenic inheritance means only males are affected

Answer 6

Y linked

Question 7

what pattern of monogenic inheritance means you inherit from mother

Answer 7

mitochondrial (always get mitochondrian DNA from mum)

Question 8

name 3 monogenic endocrine tumour syndromes

Answer 8

MEN 1, MEN 2, von hippel-lindau disease

Question 9

what gene causes MEN 1 syndrome

Answer 9

MEN 1, 11 q

Question 10

what gene causes MEN 1 syndrome

Answer 10

REY

Question 11

what gene causes von hippel lindau syndrome

Answer 11

VHL

Question 12

what tumours associated with MEN 1

Answer 12

pituitary, parathryoid, pancreatic + loads more

Question 13

what tumours are associated with MEN 2

Answer 13

thyroid medullary (C cell), adrenal chromaffin (pheochromocytoma), parathyroid hyperplasia

Question 14

what pattern of inheritance does MEN 1 and 2 follow

Answer 14

autosomal dominant

Question 15

what is the MEN 1 gene

Answer 15

a tumour suppressor

Question 16

what is the RET gene

Answer 16

proto-oncogene

Question 17

what do MEN 1 mutations cause

Answer 17

loss/ reduced protein function

Question 18

what do RET mutations cause

Answer 18

activate activation of tyrosine kinase

Question 19

why is MEN 1 so important

Answer 19

premature morbidity and mortality (50%)
considerable psychological burden
dealing with incertainty

Question 20

what are the leading causes of death in MEN 1

Answer 20

malignant pancreatic neuroendocrine tumour

thymic carcinoids

Question 21

what does mutation analysis of

MEN 1 allow

Answer 21

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

Question 22

what is the treatment for MEN 2

Answer 22

Medullary Thyroid Cancer
-Prophylactic thyroidectomy

Screening for Pheochromocytoma

screening for parathyroid disease

Question 23

where is the mutation in carney complex

Answer 23

protein kinase PKA

Question 24

what are the clinical features of carney complex

Answer 24

PPNAD (adrenal glands make excess cortisol - cushings)
acromegaly (GH producing adenoma)
thyroids carcinoma

Question 25

what are the features of mccune albright syndrome

Answer 25

Café-au-lait skin pigmentation

Precocious puberty (typically females)

Thyroid nodules
Pituitary – GH excess

Cushing’s syndrome (adrenal)

Question 26

what is the inheritance of von hippel lindau

Answer 26

autosomal dominant

Question 27

what does von hippel lindau cause

Answer 27

range of vascular tumours

Question 28

what are the features of neurofibromatosis

Answer 28

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

Question 29

where is the mutation in neurofibromatosis type 1

Answer 29

NF1 gene

Question 30

what are SDH B, C and D

Answer 30

Key mitochondial enzymes involved in succinate metabolism and Kreb’s cycle

Question 31

describe SDHD

Answer 31

causes head and neck paragangliomas

get it from Dad

Question 32

decscribe SDHB

Answer 32

causes malignant paragangliomas

B for Bad