Abstracts

Rationale: The NDE1 gene on Chromosome 16p13.11 has been associated with a wide range of phenotypes of epilepsy and neuropsychiatric disorders, including most recently fetal-brain disruption sequence, which includes agenesis of the corpus callosum and severe microcephaly. Aicardi syndrome (OMIM 304050) has classically been linked to Chromosome Xp22 without a known candidate gene. Here we present a novel case of a child with classic Aircardi Syndrome with 1.7 Mb deletion covering the NDE1 gene.Methods: The patient was followed clinically and the full phenotype was identified through clinical reports and investigations completed through the Neurology, Clinical Genetics and Ophthalmology clinics. Chromosomal microarray for this patient was completed using Agilent Oligo Array - EmArray Cyto6000 Custom Design, containing approximately 44,000 oligos. Confirmation with FISH analysis was done using BAC clone RP11-585P8.Results: The now-3 year old female patient presented in early infancy with refractory epilepsy, developing infantile spasms, with ongoing seizures and profound global developmental delay. She has bilateral microophthalmia with retinal lacunae. MRI brain imaging revealed agenesis of the corpus callosum and multiple cortical malformations. The chromosomal microarray revealed a deletion at chromosome region 16p13.11 with an estimated size of 1.706 Mb. The deletion results in the loss of one copy of three OMIM morbid map genes: NDE1(609449), ABCC6 (OMIM 603234) and MYH11 (OMIM 160745). FISH-analysis of the parental chromosome confirmed a de novo deletion.Conclusions: This case suggests a role for NDE1 gene deletions in the presentation of classic Aicardi syndrome. ABCC6 and MYH11 genes are not known to be involved in neurological disorders. This may be through gene interaction or due to haploinsufficiency with a second mutation. The likelihood of this causal association is strengthened by the recent evidence of another patient with agenesis of the corpus callosum with both a NDE1 deletion and frame shift mutation, in addition to the diverse epilepsy and neuropsychiatric phenotypes associated with NDE1 gene mutations. Further genetic studies of children with classic Aicardi syndrome are warranted.