title: Autism spectrum disorder in Phelan-McDermid syndrome: initial characterization and genotype-phenotype correlations.
abstract: BACKGROUND
  Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder associated with a terminal deletion affecting chromosome 22 (22q13) that results in the loss of function of the SHANK3 gene. SHANK3 has also been identified in gene-linkage studies to be associated with autism spectrum disorder (ASD). Diagnosis of ASD in individuals with PMS is complicated by the presence of moderate to profound global developmental delay/intellectual disability as well as other co-morbid systemic and neurological symptoms.
  
  
  METHODS
  The current study aimed to characterize the symptoms of ASD in patients with PMS and to do a preliminary exploration of genotype-ASD phenotype correlations. We conducted a standardized interview with 40 parents/guardians of children with PMS. Further, we conducted analyses on the relationship between disruption of SHANK3 and adjacent genes on specific characteristic symptoms of ASD in PMS in small subset of the sample.
  
  
  RESULTS
  The majority of PMS participants in our sample displayed persistent deficits in Social communication, but only half met diagnostic criteria under the restricted, repetitive patterns of behavior, interests, or activities domain. Furthermore, logistic regressions indicated that general developmental delay significantly contributed to the ASD diagnosis. The analyses relating the PMS genotype to the behavioral phenotype revealed additional complex relationships with contributions of genes in both deleted and preserved SHANK3 regions to the ASD phenotype and other neurobehavioral impairments.
  
  
  CONCLUSIONS
  There appears to be a unique behavioral phenotype associated with ASD in individuals with PMS. There also appears to be contributions of genes in both deleted and preserved SHANK3 regions to the ASD phenotype and other neurobehavioral impairments. Better characterization of the behavioral phenotype using additional standardized assessments and further analyses exploring the relationship between the PMS genotype and behavioral phenotype in a larger sample are warranted.
authors: Department of Neurology, Boston Children's Hospital, and Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA. loberman@lifespan.org.|Neuroplasticity and Autism Spectrum Disorder Program, E.P. Bradley Hospital and Warren Alpert Medical School of Brown University, 1011 Veterans Memorial Parkway, East Providence, RI, 02915, USA. loberman@lifespan.org.
authors: Lindsay M
authors: LM
authors: Oberman
authors: JC Self Research Institute, Greenwood Genetic Center, 113 Gregor Mendel Circle, Greenwood, SC, 29646, USA. lboccuto@ggc.org.
authors: Luigi
authors: L
authors: Boccuto
authors: JC Self Research Institute, Greenwood Genetic Center, 113 Gregor Mendel Circle, Greenwood, SC, 29646, USA. lcascio@ggc.org.
authors: Lauren
authors: L
authors: Cascio
authors: JC Self Research Institute, Greenwood Genetic Center, 113 Gregor Mendel Circle, Greenwood, SC, 29646, USA. ssarasua@ggc.org.
authors: Sara
authors: S
authors: Sarasua
authors: Department of Neurology, Boston Children's Hospital, and Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA. Walter.Kaufmann@childrens.harvard.edu.
authors: Walter E
authors: WE
authors: Kaufmann
mesh_terms: D000293:Adolescent; D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype