Paediatric genetics

Question 1

Down syndrome

Answer 1

• Trisomy 21
• Learning disability
• Congenital heart disease
• Hypothyroidism
• Immunodeficiency
• Early onset Alzheimer’s disease
• Detected via non-invasive prenatal test

Question 2

Congenital birth defect

Answer 2

• Present at birth (literally means with birth)
• Genetic or environmental or both

Question 3

Multiple Congenital Anomaly Syndromes

Answer 3

• Single gene disorders → 30%
• Chromosomal → 10%
• Teratogenic → 5%
• Idiopathic → 55%

Question 4

Diagnosis of congenital diseases (intellectual disability/ malformation syndrome)

Answer 4

• History
• Description
• Recognition of patterns
• Testing
  
  • Biochemical, chromosomal structure
  • Targeted testing
  • Trio-based exome/ genome

Question 5

Describing dysmorphic child

Answer 5

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

Question 6

Head

Answer 6

• Shape
• Size: macrocephaly and microcephaly
• Ear position → low set, posteriorly rotated

Question 7

Eyes

Answer 7

• Hypertelorism
  
  • Inner cantonal distance (ICD) and inter-pupillary distance (IPD) increased
• Telecanthus/ epicanthic fold

Question 8

Hand measurements

Answer 8

• Finger lengths
• Digital abnormalities
• Palmar creases
• Marfan syndrome, Down syndrome

Question 9

Finger descriptions

Answer 9

• Arachnodactyly → abnormally long fingers
• Brachydactyly → abnormally short fingers

Question 10

Malformations

Answer 10

• Alone or part of a syndrome

Question 11

Polysyndactyly

Answer 11

• Multiple toes contained within a single skin envelope

Question 12

Acrocephalopolysyndactylyly

Answer 12

• Tall forehead
• Polydactylyl
• Syndactylyl

Question 13

Sequence

Answer 13

• One abnormality leads to another → can have many causes
• Pierre-robin sequence → small chin to cleft palate
• Fetal akinesia sequence
  
  • Reduced foetal movement
  • Reduced breathing
  • Contractures
  • Clefting
  • Lung hypoplasia

Answer 14

• One abnormality leads to another → can have many causes
• Pierre-robin sequence → small chin to cleft palate
• Fetal akinesia sequence
  
  • Reduced foetal movement
  • Reduced breathing
  • Contractures
  • Clefting
    
    • Lung hypoplasia

Question 15

Definition of deformation and disruption

Answer 15

• Pattern of development normal start but become abnormal
• Deformation → organ parts are there
• Disruption → parts of organ/ body absent
• E..g amniotic bands

Question 16

Definition of association

Answer 16

• Two or more unrelated features occur together more than expected by change
• Unclear mechanism
• E.G VATER
  
  • Vertebral anomalites
  • Ano-rectal atresia
  • Tracheo-oesophangeal fistula
  • Radial anomalies

Question 17

Definition of syndrome

Answer 17

• Distinct group of signs and symptoms
• Often associated together and form a distinct clinical picture
• Cause may or may not be unknown

Question 18

Turner syndrome

Answer 18

• Also called 45, X → absent Y chromosome

Question 19

Clinical features of Turner’s syndrome

Answer 19

• Lymphoedema → puffy feet, nuchal translucency, cystic hygroma
• Increased carrying angle, low hairline, wide spaced nipples, sandal gap
• Short stature, occluded veins, mild learning difficulty
• Coarctation of aorta, hypothyroidism, UTI, osteoporosis and hypertension
• Primary amenorrhea and infertility

Question 20

Management of Turner syndrome

Answer 20

• Only symptomatic
• Hormonal replacement therapy to mitigate features

Question 21

Genetic investigations of learning disability

Answer 21

• Microarray
• Fragile X
• Targeted tests driven by phenotype
• Trio based exam vs trio-based genomic analysis

Question 22

22q11 deletion syndrome

Answer 22

• Cleft palate
• Abnormal facies
• Thymic hypoplasia/ immune deficiency
• Calcium abnormalities
• Heart problems
• CATCH 22 Syndrome

Question 23

Importance of phenotyping

Answer 23

• Key to assessment of clinical relevant
• Important to give accurate description of clinical features
• Diagnosis allows for future planning for family
• Help future pregnancy planning, clinical care and treatment

Answer 24

• Cleft palate
• Abnormal facies
• Thymic hypoplasia/ immune deficiency
• Calcium abnormalities
• Heart problems
• CATCH 22 Syndrome