Phenotypic Description of Autism Spectrum Disorder and Psychopathology in Maternal 15q Duplication Syndrome

Maternal 15q11-q13 duplication syndrome (Dup15q) has been associated with 0.5% of all cases of autism spectrum disorder (ASD). There is no established protocol for the neuropsychiatric evaluation of individuals with this syndrome. This study aims to define a protocol incorporating gold standard assessments. Six individuals with Dup15q underwent assessment of cognitive and adaptive functioning (Leiter-3, Adaptive Behavior Assessment System-Second Edition), autistic traits (Autism Diagnostic Observation Schedule-2 [ADOS-2], Autism Diagnostic Interview-Revised [ADI-R], Social Communication Questionnaire, Social Responsiveness Scale, Repetitive Behaviors Scale-R), co-occurring psychopathology (Kiddie Schedule for Affective Disorders and Schizophrenia, Child Behavior Checklist, Swanson, Nolan, and Pelham-Forth Edition, Sleep Disturbance Scale for Children), and family functioning (Parenting Stress Index-Short Form, PedsQL). Parents were required to fill the Symptom Checklist 90 (SCL-90) and Autism-Spectrum Quotient (AQ) to gather information about their psychiatric co-occurrences and autistic traits. A molecular analysis was performed to confirm the genetic alteration. Two siblings inherited the duplication through maternal transmission, whereas 4 individuals had a de novo maternal duplication. No participant exhibited preserved cognitive abilities; 4 of 5 showed below average adaptive functioning and 2 of 6 received a diagnosis of ASD. ADOS-2 revealed greater difficulties in the Social Affect domain compared with the Repetitive and Restricted Behaviors domain (p < 0.05), findings confirmed by ADI-R (p < 0.05). K-SADS indicated clinical scores in 5 individuals, with anxiety disorder in 3 participants. High levels of parental stress and a poor quality of life were reported. The mother carrier of the duplication showed clinical scores on the "Positive Symptom Total" of the SCL-90 and on the AQ. Individuals with an in tandem 15q-11q13 duplication seems to exhibit cognitive and adaptive difficulties along with psychiatric co-occurrences and autistic traits. Parents, with or without the duplication, may experience psychopathological difficulties and impaired family functioning.