Genetics

Question 1

Name 3 diseases with AD inheritance.

Answer 1

1. ADPKD.
2. HD.
3. Marfan’s.

Question 2

Give 6 characteristics of AD inheritance.

Answer 2

1. both homozygotes and heterozygotes manifest disease (there is no carrier state)
2. both males and females affected
3. only affected individuals can pass on disease
4. disease is passed on to 50% of children
5. normally appears in every generation (although see below)
6. risk remains same for each successive pregnancy

Question 3

Give 3 characteristics of AR inheritance.

Answer 3

1. Both parents must be carriers.
2. Often only one generation is affected.
3. 2 carrier parents have a 1 in 4 risk of having an unaffected child.

Question 4

Name 3 diseases with AR inheritance.

Answer 4

1. CF.
2. Sickle cell.
3. Haemochromatosis.

Question 5

Give an example of an X linked recessive disease.

Answer 5

Duchenne and Becker muscular dystrophy.

Question 6

Give 3 characteristics of X linked inheritance.

Answer 6

1. Male > female affected.
2. No male to male transmission.
3. Each male child of a heterozygous female carrier has a 50% chance of being affected whilst each female child of a heterozygous female carrier has a 50% chance of being a carrier.

Question 7

Give 4 examples of non-mendelian inheritance.

Answer 7

1. Multifactorial e.g. neural tube defects.
2. Mitochondrial.
3. Genomic imprinting.
4. Gonadal mosaicism.

Question 8

What is gonadal mosaicism?

Answer 8

Gonadal mosaicism is when there are two different populations of cells in the gonads. One population is normal and the other is mutated. All gametes from the mutated line are affected.

Question 9

What are the cardiac complications of Down’s syndrome?

Answer 9

1. endocardial cushion defect (most common, 40%, also known as atrioventricular septal canal defects)
2. ventricular septal defect (c. 30%)
3. secundum atrial septal defect (c. 10%)
4. tetralogy of Fallot (c. 5%)
5. isolated patent ductus arteriosus (c. 5%)

Question 10

What are some other complications on top of cardiac ones in Down’s syndrome?

Answer 10

1. subfertility: males are almost always infertile due to impaired spermatogenesis. Females are usually subfertile, and have an increased incidence of problems with pregnancy and labour
2. learning difficulties
3. short stature
4. repeated respiratory infections (+hearing impairment from glue ear)
5. Increased risk ofacute lymphoblastic leukaemia
6. Increased risk of hypothyroidism
7. Alzheimer’s disease
8. Risk of atlantoaxial instability
9. Epilepsy

Question 11

List 4 features of Patau Syndrome (trisomy 13).

Answer 11

Microcephalic, small eyes
Cleft lip/palate
Polydactyly
Scalp lesions

Question 12

List 4 features of Edward’s syndrome (trisomy 18).

Answer 12

Micrognathia
Low-set ears
Rocker bottom feet
Overlapping of fingers

Question 13

List 5 features of Fragile X.

Answer 13

Learning difficulties
Macrocephaly
Long face
Large ears
Macro-orchidism

Question 14

List 4 features of Pierre-Robin syndrome.

Answer 14

Micrognathia
Posterior displacement of the tongue (may result in upper airway obstruction)
Cleft palate

Question 15

List 3 features of Prader-Willi syndrome.

Answer 15

Hypotonia
Hypogonadism
Obesity

Question 16

List 5 features of William’s syndrome.

Answer 16

Short stature
Learning difficulties
Friendly, extrovert personality
Transient neonatal hypercalcaemia
Supravalvular aortic stenosis

Question 17

Give 9 features of CF.

Answer 17

1. neonatal period (around 20%): meconium ileus
2. recurrent chest infections (40%)
3. malabsorption (30%): steatorrhoea, failure to thrive
4. short stature
5. diabetes mellitus
6. delayed puberty
7. rectal prolapse (due to bulky stools)
8. nasal polyps
9. male infertility, female subfertility

Question 18

List 13 features of Turner syndrome.

Answer 18

1. short stature
2. shield chest, widely spaced nipples
3. webbed neck
4. congenital heart defects- bicuspid aortic valve (15%), coarctation of the aorta (5-10%)
5. primary amenorrhoea
6. cystic hygroma (often diagnosed prenatally)
7. high-arched palate
8. short fourth metacarpal
9. multiple pigmented naevi
10. lymphoedema in neonates (especially feet)
11. gonadotrophin levels will be elevated
12. hypothyroidism is much more common in Turner’s
13. horseshoe kidney: the most common renal abnormality in Turner’s syndrome
14. spoon-shaped nails
15. delayed puberty
16. recurrent otitis media

There is also an increased incidence of autoimmune disease (especially autoimmune thyroiditis) and Crohn’s disease.