Brodsky, Michael C.

Purpose To document the association of CAD-related disorder (EIEE-50) with cortical visual impairment. Observations An 8-month-old Caucasian boy with whole genome sequencing confirming 2 variants in the gene CAD, who presented with severe seizures, microcephaly, hyperreflexia, hypotonia, anemia, and severe cortical visual impairment. Magnetic resonance imaging (MRI) of the brain noted thickened cortical gray matter along the right calcarine fissure as well as changes suggesting malformation of cortical development. Empiric uridine monophosphate supplementation has significantly improved seizure activity, hypotonia, and development and has led to resolution of anemia. Conclusions and Importance CAD-related disorder is treatable and may affect visual cortical development causing severe secondary cortical visual impairment, a newly described clinical manifestation.

Abstract: Over the past 50 years, our understanding of optic nerve hypoplasia has advanced in a series of waves, with each wave producing a paradigm shift in clinical diagnosis and management. First was the recognition that optic nerve hypoplasia is a condition distinct from optic atrophy and is a frequent cause of blindness in children. Second was the identification of associated brain malformations. Third was the realization that many children with optic nerve hypoplasia have hypopituitarism. Fourth was the identification of segmental forms of optic nerve hypoplasia. Fifth was the recognition that some children are at risk for sudden death, which can often be prevented with preemptive measures. Last was the identification of additional systemic accompaniments. Genetic studies have been largely unfruitful and, for most cases, the cause remains unknown.