title: Delineating the 15q13.3 microdeletion phenotype: a case series and comprehensive review of the literature.
abstract: OBJECTIVE
  Recurrent 15q13.3 deletions are enriched in multiple neurodevelopmental conditions including intellectual disability, autism, epilepsy, and schizophrenia. However, the 15q13.3 microdeletion syndrome remains ill-defined.
  
  
  METHODS
  We systematically compiled all cases of 15q13.3 deletion published before 2014. We also examined three locally available cohorts to identify new adults with 15q13.3 deletions.
  
  
  RESULTS
  We identified a total of 246 cases (133 children, 113 adults) with deletions overlapping or within the 15q13.3 (breakpoint (BP)4-BP5) region, including seven novel adult cases from local cohorts. No BP4-BP5 deletions were identified in 23,838 adult controls. Where known, 15q13.3 deletions were typically inherited (85.4%) and disproportionately of maternal origin (P < 0.0001). Overall, 198 cases (121 children, 77 adults; 80.5%) had at least one neuropsychiatric diagnosis. Accounting for ascertainment, developmental disability/intellectual disability was present in 57.7%, epilepsy/seizures in 28.0%, speech problems in 15.9%, autism spectrum disorder in 10.9%, schizophrenia in 10.2%, mood disorder in 10.2%, and attention deficit hyperactivity disorder in 6.5%. By contrast, major congenital malformations, including congenital heart disease (2.4%), were uncommon. Placenta previa occurred in the pregnancies of four cases.
  
  
  CONCLUSIONS
  The 15q13.3 microdeletion syndrome is predominantly characterized by neuropsychiatric expression. There are implications for pre- and postnatal detection, genetic counseling, and anticipatory care.
authors: 1] Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors: Chelsea
authors: C
authors: Lowther
authors: Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors: Gregory
authors: G
authors: Costain
authors: 1] Cytogenetics Laboratory, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada [2] Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, Ontario, Canada.
authors: Dimitri J
authors: DJ
authors: Stavropoulos
authors: Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors: Rebecca
authors: R
authors: Melvin
authors: 1] Division of Cardiology, Department of Medicine, University Health Network, Toronto, Ontario, Canada [2] Division of Obstetric Medicine, Medical Disorders of Pregnancy Program, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors: Candice K
authors: CK
authors: Silversides
authors: 1] Division of Neurology, Toronto Western Hospital, Toronto, Ontario, Canada [2] Krembil Neurosciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors: Danielle M
authors: DM
authors: Andrade
authors: 1] Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, Ontario, Canada [2] Department of Clinical Genetics, Lakeridge Health Oshawa, Oshawa, Ontario, Canada.
authors: Joyce
authors: J
authors: So
authors: The Fred A. Litwin and Family Centre in Genetic Medicine, University Health Network and Mount Sinai Hospital, Toronto, Ontario, Canada.
authors: Hanna
authors: H
authors: Faghfoury
authors: 1] The Centre for Applied Genomics and Program in Genomics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada [2] Department of Molecular Genetics and McLaughlin Centre, University of Toronto, Toronto, Ontario, Canada.
authors: Anath C
authors: AC
authors: Lionel
authors: 1] The Centre for Applied Genomics and Program in Genomics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada [2] Department of Molecular Genetics and McLaughlin Centre, University of Toronto, Toronto, Ontario, Canada.
authors: Christian R
authors: CR
authors: Marshall
authors: 1] Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada [2] The Centre for Applied Genomics and Program in Genomics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada [3] Department of Molecular Genetics and McLaughlin Centre, University of Toronto, Toronto, Ontario, Canada.
authors: Stephen W
authors: SW
authors: Scherer
authors: 1] Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada [3] Division of Cardiology, Department of Medicine, University Health Network, Toronto, Ontario, Canada [4] Department of Psychiatry, University of Toronto and University Health Network, Toronto, Ontario, Canada.
authors: Anne S
authors: AS
authors: Bassett
mesh_terms: D000328:Adult; D000368:Aged; D056905:Chromosome Breakpoints; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology*; D002884:Chromosomes, Human, Pair 15; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D006720:Homozygote; D006801:Humans; D040582:Inheritance Patterns; D008607:Intellectual Disability / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D010923:Placenta Previa; D011247:Pregnancy; D015995:Prevalence; D012640:Seizures / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology*