Abstract
A 5-month-old boy was referred to the ophthalmology outpatient service after it was noted he was not making eye contact or fixing and following. He had a past medical history of bilateral hearing loss and had been born at the 0.4th centile with soft non-specific dysmorphic signs and poor feeding, but with no diagnosis. A normal ocular examination was observed apart from bilaterally sluggish pupil reactions and nystagmus with severe sight impairment. A provisional diagnosis of Leber Congenital Amaurosis was made for which genetic testing was requested.
To our surprise, the whole genome sequencing (WGS) showed a heterozygous mutation of the PEX1 gene, consistent with Zellweger Spectrum Disorder; a rare spectrum of genetic conditions grouped by a lack of functional peroxisomes. Characteristic dysmorphic features are observed in affected infants in the majority of cases. This case highlights that infants with ZSD may present with profound disability such as significant visual or auditory impairment in the absence of typical dysmorphic features. ZSD should be considered a rare differential diagnosis in the infant with significant visual impairment but a normal physical ocular examination. WGS is not yet commissioned for the diagnosis of ZSD but was pivotal for diagnosis in this patient’s case; there is a case for its inclusion to the national genome test directory.
