Genetics

Question 1

What are the 6 different forms of monogenic inheritance?

Answer 1

Autosomal dominant
Autosomal recessive
Mitochondrial
X-linked dominant
X-linked recessive
Y-linked

Question 2

How many genes are involved in a mendelian disorder?

Answer 2

Only 1 - hence MONOgenic.

Question 3

What is consanguinity?

Answer 3

When a mother and father are related.

This conveys an increased risk of autosomal recessive inheritance.

Question 4

What are Y-linked disorders fairly rare?

Answer 4

They commonly cause infertility - thus, are not passed on.

Question 5

How can a mitochondrial disease be identified?

Answer 5

Mother will be affected, along with ALL of their children.

Question 6

What are the 3 cancer ‘P’s of MEN1 syndrome?

Answer 6

Pituitary
Pancreas
Parathyroid

Question 7

What form of inheritance is observed in MEN1?

Answer 7

Autosomal dominant

Most affected will die due to this condition - often because of malignant pancreatic neuroendocrine tumors.

Question 8

Who should be tested for MEN1?

Answer 8

Those suffering from 2 or more MEN1-associated tumors
Those that have developed neuroendocrine tumors at a young age
Those with an affected relative

Question 9

What form of inheritance is seen in MEN2?

Answer 9

Autosomal dominant

Affects the RET gene

Question 10

What is the most common form of MEN2 synrome?

Answer 10

MEN2A

Question 11

What are the characteristic features of MEN2A?

Answer 11

Medullary thyroid carcinoma
Phaeochromocytoma
Parathyroid tumors

Question 12

What are the characteristic features of MEN2B?

Answer 12

Medullary thyroid carcinoma
Phaeochromocytoma
Marfanoid habitus
Mucosal neuromas

Question 13

What is the primary cause of death in MEN2?

Answer 13

Medullary thyroid carcinoma

Question 14

How is MTC diagnosed?

Answer 14

USS and FNA
Calcitonin levels (acts as a tumor marker as it is produced by C-cells)

Question 15

How is phaeochromocytoma diagnosed?

Answer 15

Elevated urinary/plasma metanephrines

Question 16

What characterises Von-Hippel Lindau syndrome?

Answer 16

Retinal and CNS hemangiomas/hemangioblastomas

Significant risk is also associated with developing clear cell renal carcinoma in these patients.

Question 17

How is Klinefelter’s Syndrome diagnosed?

Answer 17

Karyotyping - look for an additional sex chromosome.

Question 18

How does Klinefelter’s Syndrome present?

Answer 18

Will appear more feminine.

They will be infertile, with small, firm testes.

Increased risk of cryptorchidism, learning difficulties and breast cancer.

Question 19

Aside from genetic causation, what other causes exist for primary hypogonadism?

Answer 19

Medications
Infiltrative disease (e.g. haemochromatosis)
Chemotherapy
Testicular trauma

Question 20

What genetic disorder produces secondary hypogonadism?

Answer 20

Kallmann’s Syndrome

Question 21

How does Kallmann’s Syndrome present?

Answer 21

Isolated GnRH deficiency and hyposmia/anosmia
One kidney only
Red/Green colour blindness
Cleft lip

Question 22

Is Kallmann’s Syndrome or Klinefelter’s Syndrome rarer?

Answer 22

Kallmann’s is less prevalent.

Question 23

What are causes of secondary hypogonadism?

Answer 23

Kallmann’s Syndrome
Prader-Willi Syndrome
Damage to the pituitary
Obesity
Medications
Acute illness
Eating disorder

Question 24

How should a male complaining of infertility be investigated?

Answer 24

Semen analysis

Question 25

At what time of day should testosterone be measured?

Answer 25

Between 8am and 11am.

Question 26

In what individuals is testosterone therapy contraindicated?

Answer 26

Hormone responsive cancer/ prostate cancer diagnosis
Haematocrit >50%
Severe sleep apnoea/heart failure