Differences Between the Pattern of Developmental Abnormalities in Autism Associated With Duplications 15q11.2-q13 and Idiopathic Autism

• DOI: 10.1097/nen.0b013e318251f537
• Publication Date: 2012-04-06T16:38:32Z
• Authors: Jerzy Wegiel; N. Carolyn Schanen; Edwin H. Cook; Marian Sigman; W. Ted Brown; Izabela Kuchna; Krzysztof Nowicki; Jarek Wegiel; Humi Imaki; Shuang Yong Ma; Elaine Marchi; Teresa Wierzba-Bo...; Abha Chauhan; Ved Chauhan; Ira L. Cohen; Eric London; Michael Flory; Boleslaw Lach; Thomas Wisniewski
• Keywords: Adult; Male; Chromosomes, Human, Pair 15; Adolescent; Developmental Disabilities; Brain; Chromosome Mapping; Organ Size; Choristoma; Statistics, Nonparametric; Cohort Studies; Young Adult; 03 medical and health sciences; 0302 clinical medicine; Child, Preschool; Karyotyping; Chromosome Duplication; Humans; Female; Autistic Disorder; Child

The purposes of this study were to identify differences in patterns of developmental abnormalities between the brains of individuals with autism of unknown etiology and those of individuals with duplications of chromosome 15q11.2-q13 (dup[15]) and autism and to identify alterations that may contribute to seizures and sudden death in the latter. Brains of 9 subjects with dup(15), 10 with idiopathic autism, and 7 controls were examined. In the dup(15) cohort, 7 subjects (78%) had autism, 7 (78%) had seizures, and 6 (67%) had experienced sudden unexplained death. Subjects with dup(15) autism were microcephalic, with mean brain weights 300 g less (1,177 g) than those of subjects with idiopathic autism (1,477 g; p<0.001). Heterotopias in the alveus, CA4, and dentate gyrus and dysplasia in the dentate gyrus were detected in 89% of dup(15) autism cases but in only 10% of idiopathic autism cases (p < 0.001). By contrast, cerebral cortex dysplasia was detected in 50% of subjects with idiopathic autism and in no dup(15) autism cases (p<0.04). The different spectrum and higher prevalence of developmental neuropathologic findings in the dup(15) cohort than in cases with idiopathic autism may contribute to the high risk of early onset of seizures and sudden death.