Genetics

Question 1

What is the role of paediatric genetics?

Answer 1

• Diagnosis in congenital malformations and learning disability
• Approach to dysmorphic child
• Investigation into developmental delay

Question 2

What conditions is Down syndrome associated with?

Answer 2

• Learning disability
• Congenital heart disease
• Hypothyroidism
• Immunity
• Early onset Alzheimer disease

Question 3

What ethical issues are there surrounding testing for Down syndrome?

Answer 3

• Regarded as standard care in Western world
• Non-invasive testing will soon be available
• Is a world without Down syndrome acceptable?
• Screening leads to termination

Question 4

What does congenital mean?

Answer 4

• Present at birth

- Can be genetic, environmental or both

Question 5

What are the causes of multiple congenital anomaly syndromes?

Answer 5

• 55% unknown
• 30% single gene disorders
• 10% chromosomal
• 5% teratogens

Question 6

What is the epidemiology of congenital anomalies/

Answer 6

• 3% all births
• 20% children’s hospital admissions
• 30% infant deaths

Question 7

Syndrome

Answer 7

A distinct group of symptoms and signs which associated together for a characteristic clinicl picture or entitiy

Question 8

How common are multiple congenital anomalies?

Answer 8

• Individually rare

- Common as a group

Question 9

How do you diagnose a rare intellectual disability or malformation syndrome?

Answer 9

• History
• Description
• Recognition of patterns
• Testing

Question 10

What testing can be performed in diagnosis of a rare intellectual disability or malformation syndrome?

Answer 10

• Microarray standard
• Targeted testing
• Moving to exome and genome

Question 11

What should be looked at when describing a dysmorphic child?

Answer 11

• Position and shape of facial features
• Hands
• Growth of child
• General features

Question 12

What should be looked at regarding the head of a dysmorphic child?

Answer 12

• Shape
• Size: macrocephaly, microcephaly
• Ear position

Question 13

What type of ears suggest lack of maturity?

Answer 13

Low-set, posteriorly rotated

Question 14

What should be looked at regarding the eyes in a dysmorphic child?

Answer 14

Hypertelorism
-Inner canthal distance ICD and inter-pupillary distance IPD increased

Telecanthus / epicanthic folds
-ICD increased

Question 15

What hand measurements should be taken when examining a dysmorphic child?

Answer 15

• Finger length
• Digital abnormalities
• Palmar creases

Question 16

Give examples of syndromes which can affect the hands.

Answer 16

• Marfan syndrome

- Down syndrome

Question 17

How are the hands affected in Marfan’s syndrome?

Answer 17

Middle finger length divided by the total hand length is >44%

Question 18

How can malformation present?

Answer 18

Alone or part of a syndrome

Question 19

Give examples of malformation.

Answer 19

• Polysyndactylty alone (Hox D13 one cause)

- Acrocephalopolysyndatyly (Greig / GLI3)

Question 20

How does acrocephalopolysyndactyly present?

Answer 20

• Tall forehead
• Polydactyly
• Syndactyly

Question 21

Sequence

Answer 21

One abnormality leads to another and can have multiple causes

Question 22

What is Pierre-Robin sequence?

Answer 22

Small chin which leads to cleft palate

Question 23

What are the features of foetal akinesia sequence?

Answer 23

• Reduced foetal movements
• Reduced breathing
• Contractures
• Clefting
• Lung hypoplasia

Question 24

What are deformation and disruption?

Answer 24

Pattern of development normal to start with but becomes abnormal

Deformation: Organ parts are there

Disruption: Parts of organ / body part absent

Question 25

Association

Answer 25

2 features or more that occur together more often than expected by chance though the mechanism is unclear

Question 26

Give an examples of association.

Answer 26

VATER association - Vertebral anomalies - Ano-rectal atresia - Tracheo-oesphageal fistula - Radial anomalies

Question 27

What is the genetics behind Turner syndrome?

Answer 27

45, X

Question 28

How does Turner syndrome present?

Answer 28

- Lymphoedema (Puffy feet, nuchal translucency / cystic hygroma) - Increased carrying angle, low hairline, wide spaced nipples, sandal gap - Short stature, occ. v mild learning difficulties - Coarctation of aorta, hypothyroidism, UTI, osteoporosis & hypertension - Primary amenorrhoea & infertility

Question 29

How can some features of Turner syndrome be mitigated?

Answer 29

Hormone therapy

Question 30

How is learning disability investigated genetically?

Answer 30

- Microarray - Fragile X - Targeted tests driven by phenotype

Question 31

What are the features of 22q11 deletion syndrome?

Answer 31

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

Question 32

What genetic variations are common?

Answer 32

- Copy number variants | - Sequence variation