Week 4 - E - Endocrine genetics - paul newy

Question 1

Monogenic disorders are inheritance patterns due to single gene disorders What are the 6 forms of monogenic inheritance?

Answer 1

Autosomal dominant

Autosomal recessive

X-linked dominant

X-linked recessive

Y-linked

Mitochondrial

Question 2

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Answer 2

Autosomal recessive

Question 3

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Answer 3

Autosomal dominant

Question 4

If most of the offsrping affected by a disease are male, is it thought to be an autosomal or x-linked recessive inheritance?

Answer 4

Thought to be an x-linked recessive inheritance

Question 5

What chromosomes do autosome affect vs what chromosomes do x/y-linked conditions affect?

Answer 5

Autosomal conditions can affect any chromosome that is not a sex-chromosome

x/y-linked chromosomes affect the sex chromosomes

Question 6

What type of marriage do children with autosomal recessive appear?

Answer 6

Appears more frequently among the children of consanguine marriages (inbred)

Question 7

In an autosomal dominant condition, can the person be a carrier yet not be affected?

Answer 7

NO

Question 8

Can an x-linked recessive disorder be carried on from father to son?

In y-linked inheritance disorders, what sex is affected?

Answer 8

NEVER

Male

Question 9

When a female has a mutation in the mitochondrial DNA, is the trait inherited by all first pedigree offspring? What about second degree offspring?

Answer 9

in the first pedigree, you will see that when a female has the trait, all of her offspring have the trait, but in the second pedigree, this is not necessarily the case.

The expression of mitochondrial conditions is variable.

Inside each cell, there are several mitochondria.

Question 10

In mitochondrial inheritance, if a male has the trait and his spouse doesnt, will the offspring have the trait?

Answer 10

NO

Question 11

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Answer 11

X-linked dominant

X-linked cannot be carried from father to son

Question 12

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Answer 12

X-linked recessive

Question 13

There can be no carriers in an x-linked dominant or an autosomal dominant condition, therefore when there when one carrier passes on to a male and the male then is affected by the trait, is this x-lined recessive or autosomal recessive?

Answer 13

X-linked recessive as the male only has one x chromosome

Question 14

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Answer 14

Y-linked inheritance - only males affected

Question 15

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Answer 15

Mitochondiral inheritance - all offspring from affected mother have trait

Offsrping from affected father do no carry trait

Question 16

What is the name of the conditions causing benign or malignant tumours to various parts of the endocrine system?

Answer 16

MEN - multiple endocrine neoplasia

Question 17

What are the 3common tumours expressed in MEN 1?

Answer 17

The 3 common tumours are the 3Ps

Pituitary tumour

Parathyroid tumour

Pancreatic tumour

Question 18

What gene causes MEN1 and what is the mode of inheritance? What type of gene is it?

Answer 18

MEN1 gene - classical tumour suppresor gene

Autosomal dominant

Question 19

Both MEN2a and MEN2b have pheochromocytomas (tumours of the adrenal medulla) What are the tumours/features that differentiates MEN2a from MEN2b?

Answer 19

MEN2a

• Medullary thyroid cancers (Increased calcitonin)
• Parathyroid tumour,
• Pheochromocytoma

MEN2b

• Mucosal neuromas (usually on tongue or gums),
• marfinoid habitus
• Parathyroid tumour ,
• Pheochromocytoma

Question 20

What gene is affected in MEN2?

Answer 20

RET gene - classical proto-ongo gene

Autosomal dominant

Question 21

What percentage of individuals will die as a direct result of MEN1?

Answer 21

50% will die as a direct result

Question 22

Carcinoid is a rare tumour that begins in cells in the neuroendocrine system What is the neuroendocrine secretory protein used as a tumour marker for carcinoid tumours?

Answer 22

Chromagranin A - raised when there are neuroendocrine tumours

Question 23

When a child is identified to have an MEN1 mutation, what protocols are taken?

Answer 23

Reassurance to those without the familial MEN1 mutation

Periodic screening and early tumour detection in those at risk

Appropriate genetic counselling

Question 24

What is the biochemical test for an insulinoma and a gastrinoma?

Answer 24

Insulinoma - measure insuin levels whilst glucose fasting (usually 8hours without food or liquid except water)

Gastrinoma - measure gastrin levels

Question 25

In MEN2, what treatment is carried out prophylactically if there is a high risk RET mutation?

Answer 25

Prophylactic thyroidectomy due to the medullary thyroid cancer risk

Question 26

What hormonal excesses are possible in MEN1? What is the name for a gastrin secreting tumour?

Answer 26

Pituitary tumour - prolactin, IGF-1, ACTH Parathyroid - PTH Pancreatic - insulinoma, gastrinoma, glucagonoma Gastrin secreting tumour (gastrinoma) - zollinger ellison syndrome

Question 27

What hormonal excesses are usually found in MEN2?

Answer 27

Medullary thyroid cancer - C-cell cancer therefore raised calcitonin Parathyroid tumour (MEN2a)- raised PTH Pheochromocytoma - raised catecholamines (adrenaline and noradrenaline)

Question 28

Carney complex is an autosomal dominant syndrome associated with spotty pigmentation of the skin, endocrinopathy, and endocrine and nonendocrine tumors Where is the spotty pigmentation on the skin most commonly found?

Answer 28

Spotty pigmentation - lips, eyes, canthi (outer and inner corners of where upper and lower eyelid meet), penis and vagina

Question 29

What can happen due to the growth hormone secreting pituitary adenoma in carney complex and what are the locations of the myxomas? What is a myxoma?

Answer 29

Person can get acromegaly Can get heart, cutaneous and breast myxoma usually A myxoma is a benign tumour of the connective tissue

Question 30

What in the Carney complex causes cushing syndrome?

Answer 30

PPNAD - primary pigmented nodular adrenocortical disease causes the adrenal glands to produce excess cortisol leading to cushing's sydrome

Question 31

What is the gene that becomes mutated in Carney complex?

Answer 31

PRKAR1 gene

Question 32

What three factors usually make you consider a MCuney-Alright syndrome?

Answer 32

Hyperfunctioning endocrine disease Cafe-au lait skin pigmentation Fibrous dysplasia

Question 33

What does the hyperfunctioning endocrine system cause? (eg symptoms, names of conditions) What gene is mutated in McCune Albright?

Answer 33

Excess pituitary hormone prodcution Leading to - increased thyroid hormone, cortisol, estrogen and growth hormone GNAS1 mutation

Question 34

Both the mutation in Carney complex and McCune Albright cause increased C-amp signalling What is the difference in the skin symptoms between the two?

Answer 34

Carney complex causes skin pigmentation eg blue naevia spots in lips, eyes and genitalia McCune-Albright causes cafe-au lait skin and fibrous dysplasia

Question 35

Von Hippel-Lindau syndrome (VHL) is a hereditary condition associated with blood vessel tumors of the brain, spinal cord, and eye What are these tumours known as? What is the more specific name for the tumours of the eye?

Answer 35

haemangioblastomas Eye tumours are the retinal haemangiomas

Question 36

Where are the two common locations for cysts to present in Von-Hippel Lindau syndrome?

Answer 36

Pancreatic and kidney cysts

Question 37

The mutation in the VHL gene leads to accumualtion of what in VHL?

Answer 37

Gene mutation leads to accumulation of HIF proteins and stimulation of cellular proliferation

Question 38

Axillary freckling, Café-au-lait patches, Neurofibromas, Optic gliomas, Scoliosis. What are these all signs of? What is the gene that mutates in this condition?

Answer 38

Neurofibromatosis type 1 Mutated gene is NF1 gene

Question 39

What can rarely happen in NF type 1 causing sweating attacks?

Answer 39

Pheochromoctyoma can occur

Question 40

What 4 characteristics together are strongly suggestive of a pheochromocytoma?

Answer 40

headaches, palpitations, and diaphoresis (excessive sweating) in association with severe hypertension

Question 41

What conditions discussed in this flaschard set can pheochromocytoma occur in? Include the gene mutation

Answer 41

NF1 - NF1 gene mutation VHL - VHL gene mutation MEN2 - RET gene mutation

Question 42

What diseases mentioned can cause an increase in growth hormone production?

Answer 42

Carney complex McCune Albright syndrome Just a growth hormone secreting tumour causing acromegaly