title: The complex behavioral phenotype of 15q13.3 microdeletion syndrome.
abstract: Chromosome 15q13.3 represents a hotspot for genomic rearrangements due to repetitive sequences mediating nonallelic homologous recombination. Deletions of 15q13.3 have been identified in the context of multiple neurological and psychiatric disorders, but a prospective clinical and behavioral assessment of affected individuals has not yet been reported.
  
  
  
  Eighteen subjects with 15q13.3 microdeletion underwent a series of behavioral assessments, along with clinical history and physical examination, to comprehensively define their behavioral phenotypes.
  
  
  
  Cognitive deficits are the most prevalent feature in 15q13.3 deletion syndrome, with an average nonverbal IQ of 60 among the patients studied. Autism spectrum disorder was highly penetrant, with 31% of patients meeting clinical criteria and exceeding cutoff scores on both ADOS-2 and ADI-R. Affected individuals exhibited a complex pattern of behavioral abnormalities, most notably hyperactivity, attention problems, withdrawal, and externalizing symptoms, as well as impairments in functional communication, leadership, adaptive skills, and activities of daily living.
  
  
  
  The 15q13.3 deletion syndrome encompasses a heterogeneous behavioral phenotype that poses a major challenge to parents, caregivers, and treating providers. Further work to more clearly delineate genotype-phenotype relationships in 15q13.3 deletions will be important for anticipatory guidance and development of targeted therapies.Genet Med 18 11, 1111-1118.
authors.affiliation: Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Ziats
authors.affiliation: Autism Center, Texas Children's Hospital, Houston, Texas, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Robin P
authors.initials: RP
authors.lastname: Goin-Kochel
authors.affiliation: Autism Center, Texas Children's Hospital, Houston, Texas, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Leandra N
authors.initials: LN
authors.lastname: Berry
authors.affiliation: Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.|Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas, USA.
authors.forename: May
authors.initials: M
authors.lastname: Ali
authors.affiliation: Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Ge
authors.affiliation: Dan L. Duncan Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Danielle
authors.identifier: 0000-0003-3721-614X
authors.initials: D
authors.lastname: Guffey
authors.affiliation: Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Jill A
authors.identifier: 0000-0001-5664-7987
authors.initials: JA
authors.lastname: Rosenfeld
authors.affiliation: Northeast Indiana Genetics, Fort Wayne, Indiana, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Bader
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Michael J
authors.identifier: 0000-0001-6501-4962
authors.initials: MJ
authors.lastname: Gambello
authors.affiliation: Section of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Varina
authors.initials: V
authors.lastname: Wolf
authors.affiliation: Department of Pediatrics, IWK Health Centre, Halifax, Nova Scotia, Canada.
authors.forename: Lynette S
authors.initials: LS
authors.lastname: Penney
authors.affiliation: Section of Medical Genetics, Department of Pediatrics, SUNY Upstate Medical University, Syracuse, New York, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Miller
authors.affiliation: Section of Medical Genetics, Department of Pediatrics, SUNY Upstate Medical University, Syracuse, New York, USA.
authors.forename: Robert Roger
authors.initials: RR
authors.lastname: Lebel
authors.affiliation: 'Specially for Children Medical Group, Austin, Texas, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kane
authors.affiliation: Department of Pediatrics, Geisinger Medical Center, Danville, Pennsylvania, USA.
authors.forename: Kristine
authors.initials: K
authors.lastname: Bachman
authors.affiliation: University of Missouri, Columbia, Missouri, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Troxell
authors.affiliation: Section of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Clark
authors.affiliation: Dan L. Duncan Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Charles G
authors.identifier: 0000-0003-4631-6943
authors.initials: CG
authors.lastname: Minard
authors.affiliation: Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Pawel
authors.initials: P
authors.lastname: Stankiewicz
authors.affiliation: Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Beaudet
authors.affiliation: Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.|Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Christian P
authors.identifier: 0000-0002-2148-7490
authors.initials: CP
authors.lastname: Schaaf
mesh_terms: D000203:Activities of Daily Living; D000293:Adolescent; D000328:Adult; D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics* / Q000503:physiopathology; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D060825:Cognitive Dysfunction / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D010375:Pedigree; D012640:Seizures / Q000235:genetics* / Q000503:physiopathology