Abstract

Background: Recurrent microdeletions and microduplications of ~555kb at 16p11.2 confer susceptibility to autism spectrum disorder (ASD) in up to 1% of ASD patients. No physical or behavioral features have been identified that distinguish these individuals as having a distinct ASD subtype, but clinical data are limited.

Methods: We report five autistic probands identified by microarray analysis with copy number variation (CNV) of 16p11.2 (three deletions, two duplications). Each patient was assessed for ASD and dysmorphic features. We also describe a deletion-positive 26-month old female who has developmental delay (DD) and autistic features.

Results: Proband 1 (female with ASD, de novo deletion) is not dysmorphic. Proband 2 (male with autism, de novo deletion) and proband 3 and his brother (males with autism, inherited deletions) are dysmorphic, but the two probands do not resemble one another. Proband 3’s mother has mild mental retardation (MR), minor dysmorphism and meets the criteria for ASD. Proband 4 (dysmorphic autistic male, de novo duplication) had a congenital diaphragmatic hernia. Proband 5 (non-dysmorphic ASD female with a duplication) has two apparently healthy duplication-positive relatives. Probands 1 and 2 have deletion-negative siblings with ASD and Asperger syndrome, respectively. The 6th proband (a female with DD and an inherited duplication) is dysmorphic, but has oligohydramnios sequence.

Conclusions: The phenotypic spectrum associated with CNV at 16p11.2 includes ASD, MR/DD and/or possibly other primary psychiatric disorders. Compared with the microduplications, the reciprocal microdeletions are more likely to be penetrant and to be associated with non-specific major or minor dysmorphism. There are deletion-positive ASD probands with a less severe phenotype than deletion-negative ASD siblings underscoring the significant phenotypic heterogeneity.