NRXN1 deletion syndrome; phenotypic and penetrance data from 34 families

Eur J Med Genet. 2019 Mar;62(3):204-209. doi: 10.1016/j.ejmg.2018.07.015. Epub 2018 Jul 18.


The spectrum of phenotypes associated with heterozygous deletions of neurexin-1 (NRXN1) is diverse and includes: autism spectrum disorder, attention deficit hyperactivity disorder, intellectual disability, seizures, schizophrenia, mood disorders and congenital malformations. Reduced penetrance and variable expressivity of deletions in this gene remain a challenge for genetic counselling. We clinically reviewed 67 NRXN1 deletions from 34 families to document the phenotype and determine odds ratio. Thirty-four probands (5 adults, 29 children (<16 years)) were initially identified from a cohort clinically referred for arrayCGH. A further 33 NRXN1 deletions (16 with established phenotype) from the families were identified following cascade screening. Speech and language delay was a consistent clinical presentation. Pedigree analysis of the inherited group revealed numerous untested relatives with a history of mental health and developmental issues, most notably in the NRXN1β isoform patients. Our study highlights the complex nature of the NRXN1 phenotype in this population.

Keywords: 2p16.3 microdeletion; Autism spectrum disorder; Copy number variant; NRXN1 Neurexin 1.

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / pathology
  • Adolescent
  • Calcium-Binding Proteins
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Child
  • Child, Preschool
  • Female
  • Gene Deletion*
  • Humans
  • Infant
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Male
  • Mental Disorders / genetics*
  • Mental Disorders / pathology
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Neural Cell Adhesion Molecules
  • Pedigree
  • Penetrance*
  • Syndrome


  • Calcium-Binding Proteins
  • Cell Adhesion Molecules, Neuronal
  • NRXN1 protein, human
  • Nerve Tissue Proteins
  • Neural Cell Adhesion Molecules