Genetics

Question 1

examples of monogenic endocrine tumour syndromes

Answer 1

1. MEN1
2. MEN2a/b
3. NF1
4. Von Hippel Lindau
5. Carney Complex
6. McCune-Albright syndrome

Question 2

presentation of MEN1

Answer 2

3 P’s
parathyroid
pancreatic
pituitary tumours

Question 3

genetics of MEN1

Answer 3

AD condition in 11q13 (tumour suppressor)

Question 4

when is genetic testing indicated in MEN1?

Answer 4

first-degree relatives from age 5

Question 5

management of MEN1

Answer 5

expectant approach

Question 6

genetics of MEN2

Answer 6

AD mutation in RET gene in 10q (proto-oncogene)

Question 7

presentation of MEN2a

Answer 7

medullary thyroid cancer
phaeochromoctyoma
parathyroid tumours

Question 8

presentation of MEN2b

Answer 8

MTC
phaeochromocytoma
associated with marfanoid habitus, mucosal neuromas, etc.

Question 9

presentation of MEN2

Answer 9

masses
diarrhoea/flushing (mets)
paraneoplastic syndromes

Question 10

diagnosis of MEN2

Answer 10

genetics
USS-FNA
calcitonin
CEA
metanephrines
imaging

Question 11

presentation of NF1

Answer 11

axillary freckling
cafe au lait patches
neurofibromas
optic gliomas
scoliosis
learning difficulties
phaeochromocytoma

Question 12

cause of NF1

Answer 12

mutation in NF1 gene

Question 13

presentation of VHL

Answer 13

multiple vascular tumours

Question 14

genetics of VHL

Answer 14

AD mutation in VHL gene

Question 15

presentation of Carney Complex

Answer 15

spotty pigmentation of skin with many tumours

Question 16

presentation of McCune-Albright syndrome

Answer 16

cafe au lait pigmentation (Coast of Maine)
polyostotic fibrous dysplasia in bones
precocious puberty (females)
thyroid nodules
pituitary GH excess
Cushing's syndrome (adrenal)

Question 17

genetic cause of McCune-Albright syndrome

Answer 17

post-zygotic GNAS mutation leading to constitutive adenylyl cyclase signalling and overproduction of several hormones

mosaicism