Abstract

Patient NM was referred to the Geneticists following an ophthalmology appointment where dysmorphic features were noted.

Patient NM was born at 40 weeks gestation following a normal pregnancy weighing 3220 g (25th centile). His first day check was unremarkable. There is no consanguinity and his female sibling is fit and well. There is a family history of squint.

On examination, he was documented as having the following dysmorphic features: low set ears, hypertelorism, down slanting palpable fissures, broad forehead, short neck, broad chest with wide spaced nipples, foetal fingertip pads and undescended testes.

On auscultation of his chest, patient NM had a pan-systolic murmur but no other stigmata of cardiac disease. An echo showed a tiny low muscular ventricular septal defect which was of no clinical concern.

Developmental examination at 18 months revealed a globally delayed child. Patient NM was unable to walk but had been pulling to stand since 15 months. He did not have any language nor use gestures. He had only recently progressed to textured foods. There was no concern with hearing. He continued to be reviewed by the ophthalmologists for astigmatism, hypermetropia and an alternating divergent squint and he wears a pair of prescription glasses.

Genetic testing of patient NM included a microarray which revealed a 3p duplication including the RAF1 gene and a diagnosis of Noonan Syndrome was made. There is a much higher incidence of hypertrophic cardiomyopathy in patients with RAF1 mutations and therefore this investigation not only confirmed the clinical suspicion but will also determine future monitoring.

An array is a relatively new high resolution test for looking at all 46 chromosomes simultaneously and is slowing replacing the traditional karyotype. It looks for added chromosomes (duplications) or missing chromosomes (deletions) and hence specific genes that are duplicated or deleted can be identified. As in this case, it can help predict phenotype and may prevent further unnecessary investigations.

However, arrays may pick up harmless changes that are common in the general population (copy number variants) which may make interpretation difficult. It is also a more expensive test and takes longer to yield a result.