Genetics of Endocrine Disorders Flashcards
Mitochondrial disorders are inherited from which parent?
Mother
(Mitochondria from the Mother)
Which gene is related to multiple endocrine neoplasia type 1?
MEN1
Which gene is releated to multiple endocrine neoplasia type 2?
RET
The MEN1 gene is a _________ ____________ gene
The MEN1 gene is a tumour suppressor gene
Multiple endocrine neoplasia is inherited as an autosomal __________ condition
Multiple endocrine neoplasia is inherited as an autosomal dominant condition
What are the most common places for MEN type 1 to manifest?
- Parathyroid (95%)
- Pituitary (70%)
- Pancreas (50%) e.g. insulinoma, gastrinoma
- Adrenals
- Thyroid
- Bronchial
What is the most common presentation of MEN type 1?
Hypercalcaemia
(due to hyperparathyroidism)
What are the most common tumours to be associated with MEN2a?
- Medullary thyroid cancer
- Parathyroid
- Phaeochromocytoma
What are the two most common tumours associated with MEN2B?
- Medullary thyroid cancer
- Phaeochromocytoma
What are two key clinical features of MEN2B?
- Marfanoid body habitus
- Neuromas
MEN1 mutations are which type of mutations?
Loss of function
or
Reduced protein production
MEN2 mutations are which type of mutation?
Mutations which result in the activation of receptor tyrosine kinase
MEN1 mutations occur throughout the coding region
True or false?
True
RET mutations occur throughout the coding region
True or false?
False
Mutations affect specific cysteine residues
Which type of MEN has a clear phenotype/genotype correlation?
MEN2
Why is MEN1 so crucially important?
50% of patients will die as a result of the condition
What are the two leading causes of death in patients with MEN1?
- Malignant pancreatic neuroendocrine tumour
- Thymic carcinoids
What are the most common places for MEN2A to manifest?
- Parathyroid
- Medullary thyroid carcinoma
- Phaeochromocytoma (adrenal)
What are the most common places for MEN2B to manifest?
- Medullary thyroid carcinoma
- Phaeochromocytoma (adrenal)
As well as carcinoma, what are two other distinctive characteristics of MEN2B?
- Mucosal neuromas
- Marfanoid body habitus
In patients with MEN2, what is the treatment if there is a high risk RET mutation?
Prophylactic thyroidectomy
(to avoid development of medullary thyoid carcinoma)
In patients with MEN2, when is the highests risk for medullary thyroid cancer development?
< 1 year old
What is Carney Complex?
A hereditary condition associated with spotty skin pigmentation, myxomas, and benign or cancerous tumors
Why does Carney Complex often lead to the development of Cushing’s syndrome?
Craney complex manifests with primary pigmented nodular adrenocortical disease (PPNAD) - a form of bilateral adrenocortical hyperplasia
PPNAD causes adrenal glands to produce excess cortisol
In Carney Complex, it is a mutation in __________ ________ _ which leads to uncontrolled proliferation and adrenocortical hyperplasia
In Carney Complex, it is a mutation in protein kinase A which leads to uncontrolled proliferation and adrenocortical hyperplasia
What are the key clinical features of McCune-Albright Syndrome?
- Cafe-au-lait pigmentation (often in coast of Maine appearance)
- Polyostotic fibrous dysplasia (bones)
- Precocious puberty (females)
- Thyroid nodules
- GH excess (pituitary)
- Cushing’s syndrome (adrenal)
Neurofibromatosis type 1 is due to a mutation in which gene?
NF1
What are the key clinical signs and symptoms of neurofibromatosis type 1?
- Axillary freckling and cafe-au-lait patches
- Neurofibromas
- Optic gliomas
- Scoliosis
- Learning difficulties
- Phaeochromocytomas (rare)
