genetic

Question 1

what are the clinical features of Down’s syndrome?

Answer 1

• face: upslanting palpebral fissures, epicanthic folds, Brushfield spots in iris, protruding tongue, small low-set ears, round/flat face
• flat occiput
• single palmar crease, pronounced ‘sandal gap’ between big and first toe
• hypotonia
• congenital heart defects (40-50%, see below)
• duodenal atresia
• Hirschsprung’s disease

Question 2

what are the cardiac complications in Down’s syndrome?

Answer 2

• multiple cardiac problems may be present
• endocardial cushion defect (most common, 40%, also known as atrioventricular septal canal defects)
• ventricular septal defect (c. 30%)
• secundum atrial septal defect (c. 10%)
• tetralogy of Fallot (c. 5%)
• isolated patent ductus arteriosus (c. 5%)

Question 3

what are the later complications of Down’s syndrome?

Answer 3

• 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
• learning difficulties
• short stature
• repeated respiratory infections (+hearing impairment from glue ear)
• acute lymphoblastic leukaemia
• hypothyroidism
• Alzheimer’s disease
• atlantoaxial instability

Question 4

A 10-year-old boy is found to have haemophilia A following investigation for a haemoarthrosis. Which one of his relatives is most likely to have the condition?

Answer 4

Mother’s brother

X-linked recessive conditions are only seen in males

male to male transmission is not seen

Question 5

what is the genetic condition associated with Hirschsprung’s disease?

Answer 5

Down’s syndrome

section of bowel with abnormal nervous supply –> reduces normal peristaltic motion –> delayed passage of meconium + chronic constipation in childhood

Question 6

chromosome 5q deletion and typically presents with a high-pitched cry in infancy?

Answer 6

Cri du chat sydnrome

Question 7

small jaw, low-set ears, rocker-bottom feet and overlapping fingers?

Answer 7

Edward’s syndrome, trisomy 18

Question 8

mild-moderate learning difficulty, a long and narrow face, large ears, flexible fingers and large testicles?

Answer 8

Fragile-X syndrome

caused by a trinucleotide repeat expansion and is inherited in an X-linked dominant fashion

Question 9

webbed neck, pectus excavatum, short stature and pulmonary stenosis?

Answer 9

Noonan syndrome

autosomal dominant inheritance

Question 10

microcephaly, small eyes, cleft lip/palate, polydactyly and scalp lesions?

Answer 10

Patau’s syndrome (trisomy 13)

Question 11

cleft palate, posterior displacement of the tongue and a small jaw

the underlying cause of this syndrome remains poorly defined, although oligohydramnios, connective tissue disorder and genetic defects have been postulated.

Answer 11

Pierre-Robin syndrome

Question 12

spontaneous deletion on chromosome 5 in the majority of cases. Typical features include hypogonadism, hypotonia and obesity.

Answer 12

Prader-Willi syndrome

Question 13

• presence of only one X chromosome, resulting in a 45,X0 genotype.
• Patients are genetically and phenotypically female.
• presents with multiple overlapping features with Noonan syndrome although is more associated with bicuspid aortic valve and coarctation of the aorta.

Answer 13

Turner’s syndrome

Question 14

most commonly caused by a random genetic deletion on chromosome 7. Typical features include mild to moderate learning difficulty and a friendly, extroverted personality.

Answer 14

William’s syndrome

Question 15

what is the mode of inherintance for Duchenne muscular dystrophy?

Answer 15

X-linked recessive

Question 16

what are the features of Duchenne muscular dystrophy?

Answer 16

1. progressive proximal muscle weakness from 5 years
2. calf pseudohypertrophy
3. Gower’s sign: child uses arms to stand up from squatted position

Question 17

what is Duchenne muscular dystrophy associated with?

Answer 17

• dilated cardiomyopathy
• intellectual impairment (30%)

Question 18

what are dystrophinopathies due to?

Answer 18

mutation in the gene encoding dystrophin, dystrophin gene on Xp21

dystrophin is a part of a large membrane associated protein in muscle which connects the muscle membrane to actin, part of the muscle cytoskeleton

Question 19

what is the milder form of muscular dystrophy and what are its features?

Answer 19

Becker muscular dystrophy

• develops after age of 10
• intellectual impairment much less common