Congenital heart disease

Question 1

What are different causes of congenital heart disease?

Answer 1

• Copy number variation (CNV): whole chromosome, part of chromosome
• Single nucleotide variation: mendelian disorders
• CNV or SNV: charge
• Uncertain: VACTERL
• Multifactorial: isolated CHD
• Teratogens: rubella, alcohol, anti-epileptic drugs, maternal diabetes mellitus

Question 2

Features of down syndrome

Answer 2

• Trisomy 21: 95% maternal non-disjunction (maternal age), 3% translocation, 2% mosaic
• 15% atrio-ventricular septal defects
• Duodenal atresia

Question 3

How does coronary heart disease affect fetuses?

Answer 3

Increases chance of chromosome abnormality

• 19% of fetuses with CHD have abnormal chromosomes
• Associated with cystic hygroma on scan
• Only 13% of newborns with CHD have abnormal chromosomes

Question 4

Features of Turner syndrome

Answer 4

• 30% mosaic, 5% 45,X/46XY
• Coarctation of aorta
• Short stature
• Gonadal dysgenesis
• Puffy hands

Question 5

What is neck webbing

Answer 5

• Excess nuchal folds

- An indicator of prenatal cardiac difficulties

Question 6

What syndromes have neck webbing?

Answer 6

• Turner syndrome
• Noonan syndrome
• CFC syndrome
• Leopard syndrome
• Costello syndrome

Question 7

Features of Noonan syndrome

Answer 7

• Pulmonary stenosis
• Short stature
• Neck webbing
• Cryptorchidism
• Characteristic face
• PTPN11 gene (chr 12)

Question 8

Features of Cardio-facio-cutaneous syndrome (CFC)

Answer 8

• Noonan-like
  Plus:
• Ectodermal problems
• Developmental delay

Question 9

Features of Leopard syndrome

Answer 9

• Noonan-like
  Plus:
• Multiple lentigenes
• Deafness

Question 10

Features of Costello syndrome

Answer 10

- Noonan-like
Plus:
- Thickened skin folds 
- Susceptible to warts 
- Cardiomyopathy 
- Later cancer risk

Question 11

Features of 22q11 deletion syndrome

Answer 11

• C ardiac malformation
• A bnormal facies
• T hymic hypoplasia
• C left palate
• H ypoparathyroidism
• 22 q11 deletion

Renal and Psychiatric

Question 12

What 2 syndromes does 22q11 deletion syndrome encompass?

Answer 12

DiGeorge and Velocardiofacial (Shprintzen) syndromes

Question 13

Features of DiGeorge syndrome

Answer 13

• Thymic hypoplasia
• Hypoparathyroidism
• Outflow tract cardiac malformation
• Usually sporadic

Question 14

Features of Shprintzen syndrome

Answer 14

• Cleft palate/palatal insufficiency
• Outflow tract cardiac malformation
• Characteristic face
• Autosomal dominant

Question 15

Clinical features of 22q11 deletion syndrome

Answer 15

• Speech delay/palatal dysfunction common
• Very variable disorder

If 2 or more clinical features present- test

• Low frequency (1-2%) in unselected CHD
• Only around 25% are familial

Question 16

Psychiatric problems with 22q11 deletion

Answer 16

• 2% schizophrenic patients had 22q11 deletion
• 22% 22q11 deletion patients had schizophrenia
• 40 adults with 22qDS: 25% schizophrenia, 13% depression, 2.5% bipolar affective

Question 17

How is 22q deletion a genomic disease?

Answer 17

• Low copy number repeats

- Predispose to deletion and translocation (e.g. t11;22)

Question 18

Features of Williams syndrome (creepy face)

Answer 18

• Aortic stenosis (supravalvar)
• Hypercalcemia
• 5th finger clinodactyly
• Characteristic face
• Cocktail party manner
• Deletion of elastin on chromosome 7
• Deletion of contiguous genes
• LIM kinase

Question 19

Features of Teratogens

Answer 19

• Fetal alcohol syndrome: ADHD, 3-5 units per week
• Antiepileptic drugs
• Rubella
• Maternal diabetes, Mellitus

Question 20

What is ventricular septal defect associated with?

Answer 20

VSD is associated with folate deficiency

• Periconceptual multivitamin use and nonsyndromic cardiac defects
• MTHFR and CHD