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Abstract

Background Heterozygous mutations in CNTNAP2 have been identified in patients with a range of complex phenotypes including intellectual disability, autism and schizophrenia. However heterozygous CNTNAP2 mutations are also common in the normal population. Conversely, homozygous mutations are rare and have not been found in unaffected individuals. Case presentation We describe a consanguineous family carrying a deletion in CNTNAP2 predicted to abolish function of its protein product, CASPR2. Affected family members show epilepsy, facial dysmorphisms, severe intellectual disability and impaired language. We compared these patients with previously reported individuals carrying homozygous mutations in CNTNAP2 and identified a highly recognisable phenotype. Conclusions We propose that CASPR2 loss produces a syndrome involving early-onset refractory epilepsy, intellectual disability, language impairment and autistic features that can be recognized as CASPR2 deficiency disorder. Further screening for homozygous patients meeting these criteria, together with detailed phenotypic investigations will be crucial for understanding the contribution of CNTNAP2 to normal and disrupted development.