title: Subtypes in 22q11.2 deletion syndrome associated with behaviour and neurofacial morphology.
abstract: 22q11.2 deletion syndrome (22q11DS) has a complex phenotype with more than 180 characteristics, including cardiac anomalies, cleft palate, intellectual disabilities, a typical facial morphology, and mental health problems. However, the variable phenotype makes it difficult to predict clinical outcome, such as the high prevalence of psychosis among adults with 22q11DS (~25-30% vs. ~1% in the general population). The purpose of this study was to investigate whether subtypes exist among people with 22q11DS, with a similar phenotype and an increased risk of developing mental health problems. Physical, cognitive and behavioural data from 50 children and adolescents with 22q11DS were included in a k-means cluster analysis. Two distinct phenotypes were identified: Type-1 presented with a more severe phenotype including significantly impaired verbal memory, lower intellectual and academic ability, as well as statistically significant reduced total brain volume. In addition, we identified a trend effect for reduced temporal grey matter. Type-1 also presented with autism-spectrum traits, whereas Type-2 could be described as having more 22q11DS-typical face morphology, being predominately affected by executive function deficits, but otherwise being relatively high functioning with regard to cognition and behaviour. The confirmation of well-defined subtypes in 22q11DS can lead to better prognostic information enabling early identification of people with 22q11DS at high risk of psychiatric disorders. The identification of subtypes in a group of people with a relatively homogenous genetic deletion such as 22q11DS is also valuable to understand clinical outcomes.
authors.affiliation: School of Medicine and Public Health, University of Newcastle, New South Wales, Australia. Brooke.Sinderberry@newcastle.edu.au
authors.forename: Brooke
authors.initials: B
authors.lastname: Sinderberry
authors.forename: Scott
authors.initials: S
authors.lastname: Brown
authors.forename: Peter
authors.initials: P
authors.lastname: Hammond
authors.forename: Angela F
authors.initials: AF
authors.lastname: Stevens
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schall
authors.forename: Declan G M
authors.initials: DG
authors.lastname: Murphy
authors.forename: Kieran C
authors.initials: KC
authors.lastname: Murphy
authors.forename: Linda E
authors.initials: LE
authors.lastname: Campbell
mesh_terms: D000293:Adolescent; D001921:Brain / Q000473:pathology; D002648:Child; D002653:Child Behavior Disorders / Q000453:epidemiology / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22; D016000:Cluster Analysis; D015331:Cohort Studies; D004062:DiGeorge Syndrome / Q000145:classification* / Q000453:epidemiology / Q000473:pathology*; D056344:Executive Function; D005145:Face / Q000473:pathology; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000453:epidemiology / Q000235:genetics; D008297:Male; D001523:Mental Disorders / Q000453:epidemiology / Q000235:genetics*; D009483:Neuropsychological Tests; D010641:Phenotype; D015995:Prevalence; D012307:Risk Factors; D012919:Social Behavior