Toward better characterization of restricted and repetitive behaviors in individuals with germline heterozygous PTEN mutations. American journal of medical genetics. Part A Uljarevic, M., Frazier, T. W., Rached, G., Busch, R. M., Klaas, P., Srivastava, S., Martinez-Agosto, J. A., Sahin, M., Eng, C., Hardan, A. Y., Developmental Synaptopathies Consortium 2021


This study aimed to further our understanding of restricted and repetitive behaviors (RRB) among individuals with germline pathogenic mutations in PTEN by providing multimethod characterization and comparison of key RRB subdomains across individuals with PTEN mutations with autism spectrum disorder (ASD) (PTEN-ASD), with PTEN mutations without ASD (PTEN-No ASD) and with ASD and macrocephaly but without PTEN mutations (Macro-ASD). Of 86 total research participants, 38 had PTEN-ASD (Mage =8.93years, SDage =4.75), 25 Macro-ASD (Mage =11.99years; SDage =5.15), and 23 PTEN-No ASD (Mage =8.94years; SDage =4.85). The Repetitive Behavior Scale-Revised (RBS-R) and the Autism Diagnostic Interview-Revised (ADI-R) were used as measures of distinct RRB domains. There were significant group differences in the RBS-R repetitive motor behaviors (RMB; F=4.52, p=0.014, omega2 =0.08), insistence on sameness (IS; F=4.11, p=0.02, omega2 =0.05), and circumscribed interests (CI; F=7.80, p=0.001, omega2 =0.14) scales. Post hoc comparisons showed that the PTEN-No ASD group had significantly lower RMB, IS, and CI scores compared to both PTEN-ASD and Macro-ASD groups. Importantly, PTEN-No ASD group still showed elevated RRB levels. Furthermore, there was a portion of individuals in PTEN-No ASD group whose Full-Scale Intelligence Quotient (FSIQ) was >70 that did not show floor level scores in the RMB domain. After adjusting for age and FSIQ scores, group differences were no longer statistically significant. RMB, IS, and CI domains showed distinct association patterns with sex, age, and FSIQ. This investigation provides the largest and most comprehensive characterization of distinct RRB domains in individuals with PTEN mutations to date. Despite the limitations, our findings have important assessment and treatment implications.

View details for DOI 10.1002/ajmg.a.62458

View details for PubMedID 34423884