Paediatric Genetics

Question 1

What are some conditions that patients suffering from down sydrome are perdisposed to?

Answer 1

Congenital heart disease

Weakened immunity

Early onset Alzheimer’s

Hypothyroidism

Question 2

What are some worrying head features that may be seen in children with developmental abnormalities?

Answer 2

abnormal shape of the head

Macro / microcephaly

Ear position is abnormal - low set and posteriorly roated indicates lack of maturity

Question 3

What are some commonly seen eye abnormalities in children with genetic syndromes?

Answer 3

Hypertelorism - increased space between eyes

Telecanthus / epicanthic folds -

Hypotelorism

Question 4

What are some commonly seen hand abnormalities in children with genetic syndromes? What syndromes may cause these abnormalities?

Answer 4

Finger length abnormalities
- arachnodactyly (long) / brachydactyly (short)
Digital abnormalities
Palmar crease number abmormality

Downs / Marfans

Question 5

What is polysyndactyly?

Answer 5

More digits than you should have (6+) with some of the digits being stuck togethet

poly - more
syn - stuck together
dactyly - fingers

Question 6

What is acrocephalopolysyndactyly?

Answer 6

Syndrome consisting of:

• Tall forehead
• More digits than normal
• Some of the digits stuck together

Question 7

What is fetal akinesia?

Answer 7

Fetal akinesia deformation sequence (FADS) is a condition characterized by decreased fetal movement (fetal akinesia) as well as intra-uterine growth restriction (IUGR), multiple joint contractures (arthrogryposis), facial anomalies, underdevelopment of the lungs (pulmonary hypoplasia) and other developmental abnormalities

Question 8

What are deformation & disruption with regards to genetic abnormalities?

Answer 8

Deformation - part of the organ are there but underdeveloped / incorrectly developed

Disruption - parts of the organ / body are absent

Question 9

What is aplasia?

Answer 9

The failure of an organ or tissue to develop correctly

Question 10

What is VATER syndrome?

Answer 10

Syndrome composed of:

• Vertebral abnormalities
• Ano-rectal atresia
• Treacheo-oesophageal fistula
• Radial anomalies (aplasia)

Question 11

What is atresia?

Answer 11

Where an orifice or passage in the body is abnormally closed or absent

Question 12

What genetic abnormality results in Turner syndrome?

Answer 12

Presence of an X but no Y chromosome

also called 45 X

Question 13

What are some of the cardinal features of Turner syndrome?

Answer 13

Lymphoedema (puffy feet, nuchal translucency, cystic hygroma)

Short stature, mild learning difficulty

Low hairline at the back, increased space between nipples

Sandal gap deformity

Question 14

What are some conditions that are closely associated with Turner syndrome?

Answer 14

Coarctation of the aorta

Hypothyroidism

** Primary amenorrhoea and infertility

UTI / osteoporosis / hypertension

Question 15

What are the first steps towards investigating a suspected learning disability?

Answer 15

Microarray (chromosome # and complement)

Fragile X gene analysis

• From there proceed to targetted tests determined by the phenotype of the child

Question 16

How does 22q11 syndrome tend to present?

Answer 16

CATCH 22:

• Cleft palate
• Abnormal facies
• Thymic hypoplasia / immune deficiency
• Calcium abnormalities
• Heart problems

Question 17

If you’re struggling to make a diagnosis based on the syndrome and you don’t know which specific tests to do, what broad genetic testing options are out there?

Answer 17

Trio based exome sequencing (exome - parts that code for proteins)

Trio based genome sequencing

Question 18

How can you narrow down which genes are negatively affecting the patient with genome / exome sequencing?

Answer 18

1. Sequence the genome and find variants
2. Compare with database to find which variants are rare
3. Of those variants, which code for proteins?
4. Of the protein coding ones, which mutations are present in child and not parents?
5. Which of these genes are mutated in known disorders?

Question 19

With regards to diagnosing genetic syndromes, what is the main role of the doctor?

Answer 19

Establishing a comprehensive phenotype description through examination and investigations