Congenital anomalies and dysmorphic newborn assessment — formative SAQs

SAQ 1 (10 marks)

A term newborn is noted to be hypotonic with a flat facial profile, upslanting palpebral fissures, and a single palmar crease. On day two the baby begins to vomit green fluid. [3]

1. What is the most likely syndromic diagnosis, and which chromosomal abnormality underlies it? (2) [3]
2. Outline the immediate management of the bilious vomiting. (4) [3]
3. List four associated conditions this baby must be screened for during the neonatal period. (4) [3]

Model answer

1. The clinical picture is Down syndrome (Trisomy 21). The flat facial profile, upslanting palpebral fissures, hypotonia, and single palmar crease form the recognisable pattern; the underlying cause is a third copy of chromosome 21, usually from non-disjunction. [3]

2. Bilious (green) vomiting in a newborn is a surgical emergency. Make the baby nil-by-mouth, pass a nasogastric tube on free drainage, establish intravenous access, and correct fluid and electrolyte losses. In Trisomy 21 the classic cause is duodenal atresia (the "double bubble" on an abdominal X-ray), so obtain urgent imaging and refer to paediatric surgery. [3]

3. Four conditions to screen for: an atrioventricular septal defect or other congenital heart disease (echocardiogram on every baby), congenital hypothyroidism, congenital hearing loss (hearing screen), and duodenal or gastrointestinal atresia. Ongoing surveillance also covers developmental delay and atlanto-axial instability later in childhood. [3]

SAQ 2 (10 marks)

A dysmorphic newborn has multiple congenital anomalies with no obvious syndromic diagnosis at the bedside. The baby is clinically stable. [1] [2]

1. Justify the choice of chromosomal microarray as the first-tier genetic test over a standard karyotype. (3) [2]
2. Outline the circumstances under which you would escalate to rapid whole-genome or exome sequencing. (4) [11]
3. Describe how you would counsel the parents about the meaning of a normal microarray result. (3) [1]

Model answer

1. Chromosomal microarray detects sub-microscopic copy-number variants — deletions and duplications — that a standard karyotype cannot resolve. For a child with multiple congenital anomalies of unknown cause, microarray has a higher diagnostic yield than karyotype and is recommended as a first-tier test by consensus guidelines. Karyotype is reserved for cases where a whole-chromosome aneuploidy is clinically suspected. [2]

2. Escalate to rapid exome or genome sequencing when the infant is critically ill in a neonatal intensive care setting with a suspected monogenic disorder, when the microarray is unrevealing, and when a timely molecular diagnosis could change acute management. The NSIGHT1 trial showed that rapid whole-genome sequencing increases the proportion of infants receiving an etiologic diagnosis within a clinically useful timeframe. [11]

3. A normal microarray reduces but does not eliminate the probability of a genetic cause, because it does not detect single-nucleotide variants or balanced rearrangements. Explain to the parents that the most common copy-number causes have been excluded, that further testing (such as exome or genome sequencing) may be considered as it becomes available, and that ongoing clinical and developmental follow-up remains important. Keep the door open for re-analysis as the phenotype evolves and testing improves. [1] [2]