Homozygous exonic and intragenic NRXN1 deletion presenting as either West syndrome or autism spectrum disorder in two siblings

Neurexins (NRXNs) are cell-adhesion molecules that play critical roles in establishing and maintaining synaptic connections. Humans have three NRXN genes (NRXN1, NRXN2, NRXN3) and heterozygous intragenic microdeletions involving NRXN1 have been associated with autism spectrum disorder, attention deficit hyperactivity disorder, intellectual disability, seizures, schizophrenia, and bipolar disorder. Bi-allelic loss in NRXN1 produces a recessive and severe phenotype. We would like to describe the clinical, electroencephalographic, and genetic findings of two siblings, one with a neurodevelopmental disorder with infantile spasms and the other with autism spectrum disorder, having homozygous exonic NRXN1 deletion. A suspicious variant was not detected in the whole exome-sequencing but copy number variation analysis revealed NRXN1 exon 2–5 homozygous deletion (chr2:51149007–51255411; 106.404 kb) in both siblings. Neurodevelopmental disorder with infantile spasms and autism spectrum disorder in two siblings with homozygous NRXN1 deletion display intrafamilial phenotypic variation. Bi-allelic/homozygous NRXN1 exonic deletions are responsible for a spectrum from significant intellectual disability to epileptic encephalopathy, even within the same family. Array comparative genomic hybridization should be the first genetic testing in epileptic encephalopathy although we reached the diagnosis with next-generation sequencing and later copy number variation analysis. •Neurexin 1 (NRXN1) has a fundamental role in synaptogenesis and synaptic maintenance.•Heterozygous deletions/mutations in the NRXN1 gene have been associated with psychiatric disorders.•A severe phenotype including hypotonia, severe developmental delay is the result of bi-allelic NRXN1 deficiency.•Two siblings with homozygous intragenic NRXN1 deletion in the present article reveal intrafamilial phenotypic variation.•Copy number variation analysis of next-generation sequencing data is beneficial in bi-allelic NRXN1 deletions’ diagnosis.