Paediatric Genetics

Question 1

What can multiple congenital anomalies occur due to?

Answer 1

Multiple congenital anomaly syndromes can occur:

• Single gene disorders 30%
• Chromosomal 10%
• Teratogens 5%
• Unknown 55%

These individually are rare, but common as a group

Question 2

What is a syndrome?

Answer 2

Syndrome = pattern of clinical features occurring together

Question 3

Multiple congenital anamaly syndromes - epidemiology

(prevalence of births)

Answer 3

• 3% of all births

Question 4

How many genes are there?

Answer 4

22,000

Question 5

What is the diagnosis of rare genetic conditions done by?

Answer 5

• History
• Description
• Recognition of patterns
• Testing
  
  • Standard
    
    • Biochemical, chromosome structure (microarray standard)
  • Targeted testing
  • Moving to trio-based exome/genome

Question 6

How do you describe a dysmorphic child?

Answer 6

• Position and shape of facial features
  
  • Head – shape, size (macrocephaly, microcephaly), ear position (low set, posteriorly rotated)
  • Eyes – hypertelorism (eyes distant from each other), telecanthus/epicanthic folds
• Hands (examples down syndrome, marfan syndrome)
  
  • Finger length
  • Digital abnormalities
  • Palmar creases
• Growth of child
• Growth features

Question 7

What is the medical term for eyes distant from each other?

Answer 7

Hypertelorism

Question 8

What is a malformation?

Answer 8

Can occur alone or part of a syndrome

Examples:

• Polysyndactylty alone
  
  • Hox D13 one cause
• Or acrocephalopolysyndatyly
  
  • Greig/GLI3

Question 9

What are examples of malformation?

Answer 9

• Polysyndactylty alone
  
  • Hox D13 one cause
• Or acrocephalopolysyndatyly
  
  • Greig/GLI3

Question 10

What is a sequence?

Answer 10

Is where one abnormality leads to another, can have multiple causes

Examples:

• Pierre-Robin sequence
  
  • Small chin to cleft palate
• Fetal akinesia sequence
  
  • Reduced fetal movement
  • Reduced breathing
  • Contractures
  • Clefting
  • Lung hypoplasia

Question 11

What are examples of sequences?

Answer 11

• Pierre-Robin sequence
  
  • Small chin to cleft palate
• Fetal akinesia sequence
  
  • Reduced fetal movement
  • Reduced breathing
  • Contractures
  • Clefting
  • Lung hypoplasia

Question 12

What is deformation and disruption?

Answer 12

Pattern of development normal to start with but becomes abnormal

Question 13

What is the meaning of:

• deformation
• disruption

Answer 13

Deformation = organ parts there

Disruption = parts of organ/body missing

Question 14

What is an example of a deformation and disruption?

Answer 14

• Amniotic bands

Question 15

What is an association?

Answer 15

Two features or more occur together more often than expected by change through an unclear mechanism

Examples are VATER:

• Vertebral anomalies
• Ano-rectal atresia
• Tracheo-oesophageal fistula
• Radial anomalies

Question 16

What is an example of an association?

Answer 16

Examples are VATER:

• Vertebral anomalies
• Ano-rectal atresia
• Tracheo-oesophageal fistula
• Radial anomalies

Question 17

What is a syndrome?

Answer 17

A distinct group of symptoms and signs which, associated together, form a characteristic clinical picture or entity

Question 18

What are common syndromes?

Answer 18

• Down syndrome (Trisomy 21)
• Trisomy 13
• Trisomy 18
• Turner’s syndrome (45X)

Question 19

Down syndrome - aetiology

Answer 19

• Trisomy 21

Question 20

Down syndrome - presentation

Answer 20

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

Question 21

Turner’s syndrome - aetiology

Answer 21

• Genetic
  
  • 45, X

Question 22

Turner’s syndrome - features

Answer 22

• Increased carrying angle, low hairline, wide sp nipples, sandal gap
• Short stature
• Occasionally mild learning disability
• Coarctation of aorta, hypothyroidism, UTI, osteoporosis and hypertension
• Primary amenorrhoea

Question 23

Turner’s syndrome - treatment

Answer 23

• Hormonal therapy mitigates some features

Question 24

What ivnestigations are done for learning disability syndromes?

Answer 24

• Microarray
• Fragile X
• Targeted tests driven by phenotype
• Trio based exome vs trio-base genome analysis
  
  • Funding an issue

Question 25

What is an example of a learning disability syndrome?

Answer 25

* 22q11 deletion

Question 26

22q11 deletion syndrome - features

Answer 26

* Cleft palate * Abnormal facies * Trymic hypoplasia/immune deficiency * Calcium * Heart problems * Caused by 22 deletion

Question 27

Why is phenotyping important?

Answer 27

In genetic analysis, most of the variations do not have clinical manifestations: * Need to focus on ones that do * Can be done by comparing genome to parents * Phenotyping (accurate description of features)