Genetics of Endocrine Disorders

Question 1

Mitochondrial disorders are inherited from which parent?

Answer 1

Mother

(Mitochondria from the Mother)

Question 2

Which gene is related to multiple endocrine neoplasia type 1?

Answer 2

MEN1

Question 3

Which gene is releated to multiple endocrine neoplasia type 2?

Answer 3

RET

Question 4

The MEN1 gene is a _________ ____________ gene

Answer 4

The MEN1 gene is a tumour suppressor gene

Question 5

Multiple endocrine neoplasia is inherited as an autosomal __________ condition

Answer 5

Multiple endocrine neoplasia is inherited as an autosomal dominant condition

Question 6

What are the most common places for MEN type 1 to manifest?

Answer 6

1. Parathyroid (95%)
2. Pituitary (70%)
3. Pancreas (50%) e.g. insulinoma, gastrinoma
4. Adrenals
5. Thyroid
6. Bronchial

Question 7

What is the most common presentation of MEN type 1?

Answer 7

Hypercalcaemia

(due to hyperparathyroidism)

Question 8

What are the most common tumours to be associated with MEN2a?

Answer 8

1. Medullary thyroid cancer
2. Parathyroid
3. Phaeochromocytoma

Question 9

What are the two most common tumours associated with MEN2B?

Answer 9

1. Medullary thyroid cancer
2. Phaeochromocytoma

Question 10

What are two key clinical features of MEN2B?

Answer 10

1. Marfanoid body habitus
2. Neuromas

Question 11

MEN1 mutations are which type of mutations?

Answer 11

Loss of function

or

Reduced protein production

Question 12

MEN2 mutations are which type of mutation?

Answer 12

Mutations which result in the activation of receptor tyrosine kinase

Question 13

MEN1 mutations occur throughout the coding region

True or false?

Answer 13

True

Question 14

RET mutations occur throughout the coding region

True or false?

Answer 14

False

Mutations affect specific cysteine residues

Question 15

Which type of MEN has a clear phenotype/genotype correlation?

Answer 15

MEN2

Question 16

Why is MEN1 so crucially important?

Answer 16

50% of patients will die as a result of the condition

Question 17

What are the two leading causes of death in patients with MEN1?

Answer 17

1. Malignant pancreatic neuroendocrine tumour
2. Thymic carcinoids

Question 18

What are the most common places for MEN2A to manifest?

Answer 18

1. Parathyroid
2. Medullary thyroid carcinoma
3. Phaeochromocytoma (adrenal)

Question 19

What are the most common places for MEN2B to manifest?

Answer 19

1. Medullary thyroid carcinoma
2. Phaeochromocytoma (adrenal)

Question 20

As well as carcinoma, what are two other distinctive characteristics of MEN2B?

Answer 20

1. Mucosal neuromas
2. Marfanoid body habitus

Question 21

In patients with MEN2, what is the treatment if there is a high risk RET mutation?

Answer 21

Prophylactic thyroidectomy

(to avoid development of medullary thyoid carcinoma)

Question 22

In patients with MEN2, when is the highests risk for medullary thyroid cancer development?

Answer 22

< 1 year old

Question 23

What is Carney Complex?

Answer 23

A hereditary condition associated with spotty skin pigmentation, myxomas, and benign or cancerous tumors

Question 24

Why does Carney Complex often lead to the development of Cushing’s syndrome?

Answer 24

Craney complex manifests with primary pigmented nodular adrenocortical disease (PPNAD) - a form of bilateral adrenocortical hyperplasia

PPNAD causes adrenal glands to produce excess cortisol

Question 25

In Carney Complex, it is a mutation in __________ \_\_\_\_\_\_\_\_ _ which leads to uncontrolled proliferation and adrenocortical hyperplasia

Answer 25

In Carney Complex, it is a mutation in **protein kinase A** which leads to uncontrolled proliferation and adrenocortical hyperplasia

Question 26

What are the key clinical features of McCune-Albright Syndrome?

Answer 26

1. Cafe-au-lait pigmentation (often in coast of Maine appearance) 2. Polyostotic fibrous dysplasia (bones) 3. Precocious puberty (females) 4. Thyroid nodules 5. GH excess (pituitary) 6. Cushing's syndrome (adrenal)

Question 27

Neurofibromatosis type 1 is due to a mutation in which gene?

Answer 27

NF1

Question 28

What are the key clinical signs and symptoms of neurofibromatosis type 1?

Answer 28

1. Axillary freckling and cafe-au-lait patches 2. Neurofibromas 3. Optic gliomas 4. Scoliosis 5. Learning difficulties 6. Phaeochromocytomas (rare)