The Phenotypic Spectrum of 15q13.3 Region Duplications: Report of 5 Patients

Abstract

Chromosome 15q13.3 microduplications are associated with a wide spectrum of clinical presentations ranging from normal to different neuropsychiatric conditions, such as developmental delay (DD), intellectual disability (ID), epilepsy, hypotonia, autism spectrum disorders (ASD), attention-deficit hyperactivity disorder, and schizophrenia. The smallest region of overlap for 15q13.3 duplications encompasses the Cholinergic Receptor Nicotinic Alpha 7 Subunit (CHRNA7) gene, a strong candidate for the behavioral abnormalities. We report on a series of five patients with 15q13.3 duplications detected by chromosomal microarray. The size of the duplications ranged from 378 to 537 kb, and involved the CHRNA7 gene in all patients. The most common clinical features, present in all patients, were speech delay, autistic behavior, and muscle hypotonia; DD/ID was present in three patients. One patient presented epileptic seizures; EEG anomalies were observed in three patients. No consistent dysmorphic features were noted. Neuroimaging studies revealed anomalies in two patients: Dandy–Walker malformation and a right temporal cyst. 15q13.3 duplications are associated with various neuropsychiatric features, including speech delay, hypotonia, ASD, and ID, also present in our patient group. Our study brings detailed clinical and molecular data from five ASD patients with 15q13.3 microduplications involving the CHRNA7 gene, contributing to the existing knowledge about the association of 15q13.3 duplications with neuropsychiatric phenotypes.