title: Characterisation of CASPR2 deficiency disorder--a syndrome involving autism, epilepsy and language impairment.
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 found in the normal population. Conversely, homozygous mutations are rare in patient populations and have not been found in any unaffected individuals.
  
  
  METHODS
  We describe a consanguineous family carrying a deletion in CNTNAP2 predicted to abolish function of its protein product, CASPR2. Homozygous family members display 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 and molecular investigations will be crucial for understanding the contribution of CNTNAP2 to normal and disrupted development.
authors: Max Planck Institute for Psycholinguistics, PO Box 310, Nijmegen, 6500, AH, The Netherlands. Pedro.Cuadrado@mpi.nl.
authors: Pedro
authors: P
authors: Rodenas-Cuadrado
authors: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy. nicolapietrafusa@gmail.com.
authors: Nicola
authors: N
authors: Pietrafusa
authors: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy. teresafrancavilla@icloud.com.
authors: Teresa
authors: T
authors: Francavilla
authors: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy. centroepilessia.neurologia@uniba.it.
authors: Angela
authors: A
authors: La Neve
authors: Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, "G. Gaslini" Institute, Genoa, Italy. strianop@gmail.com.
authors: Pasquale
authors: P
authors: Striano
authors: Max Planck Institute for Psycholinguistics, PO Box 310, Nijmegen, 6500, AH, The Netherlands. Sonja.Vernes@mpi.nl.|Donders Centre for Cognitive Neuroimaging, Kapittelweg 29, Nijmegen, 6525, EN, The Netherlands. Sonja.Vernes@mpi.nl.
authors: Sonja C
authors: SC
authors: Vernes
mesh_terms: D001321:Autistic Disorder / Q000235:genetics*; D002675:Child, Preschool; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D007806:Language Disorders / Q000235:genetics; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA; D013577:Syndrome
chemical_list: C403049:CNTNAP2 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins