The complex behavioral phenotype of 15q13.3 microdeletion syndrome

Background: Chromosome 15q13.3 represents a hotspot for genothic 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. Methods: 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. Results: 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. Conclusions: 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.