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The purpose of this study is to determine cross-sectional and longitudinal medical, behavioral, and cognitive differences between PTEN ASD and other groups, as well as to identify cognitive, neural systems, and molecular biomarkers specific to PTEN ASD. In addition, this study will be creating and maintaining a biorepository and linked phenotypic database for PTEN ASD.


PTEN, ASD, Autism, Macrocephaly, PTEN Hamartoma Tumor Syndrome

Recruitment Status


Detailed Description

Autism spectrum disorders (ASD) are a set of neurodevelopmental disorders characterized by social communication/interaction impairments and restricted/repetitive behaviors. ASD associated with germline heterozygous PTEN mutations (PTEN ASD) is a genetically defined sub-group that, may be one of the more prevalent genetic disorders contributing to ASD (0.5-2%). The purpose of this research study is to carefully track the phenotypic and molecular characteristics of PTEN ASD and identify biomarkers for intervention studies. Individuals with PTEN ASD, with macrocephalic ASD without a PTEN mutation (macro-ASD), healthy controls, and individuals with PTEN mutations without ASD (PTEN no-ASD) will be asked to participate in this study if they are 18 months and older. Both males and females will be asked to participate. Additionally, to be eligible for study participation, individuals' primary communicative language must be English. The study involves 3 on site visits over the course of two years. Study visits will vary in length from about 4 hours to 6 hours. Study visits involve a physical exam, medical history questions, neuropsychological assessments, and a blood draw done for laboratory studies. A subset of participants between the ages of 2 and 11 years old will take part in the EEG portion of the study. Individuals who have a clinically indicated MRI will have an option to provide routine clinical scans for analysis.

Eligibility Criteria

Inclusion Criteria

Individuals above the age of 18 months old at the time of consent who have documentation of a clinical diagnosis of autism spectrum disorder and/or a verified PTEN mutation from a medical or mental health professional for inclusion in the PTEN ASD, PTEN no-ASD or ASD macrocephaly groups.
Macrocephaly (head circumference greater than or equal to 98th percentile) for inclusion in the ASD macrocephaly group.
For youths, consent from parents or legal guardian. For adults, consent from self or legal guardian.
Youths who are able (some young or severely impaired participants may not be able to provide assent) will be asked to provide assent as per IRB guidelines.
Families with multiple children who meet the above inclusion criteria will be permitted to have as many children participate as they wish. A separate consent form will be filled out for each child enrolled in the study.
Primary communicative language must be English

Exclusion Criteria

Unwilling or unable to comply with study procedures and assessments
Clinically significant medical disease that would prohibit participation in the study procedures.
For subjects ELIGIBLE FOR OPTIONAL imaging biomarker assessment: contraindications to 3T MRI scanning, such as metal implants/non-compatible medical devices or medical conditions, including vagus nerve stimulator.
For subjects ELIGIBLE FOR EEG/ERP biomarker assessment: contraindications to EEG/ERP, such as uncooperative or destructive behaviors preventing lead placement or capture by ERP/VEP equipment. Under age 2 or over 11 at the time of enrollment.



Min Age

18 Months

Max Age


Download Date

November 13, 2023

Principal Investigator

Mustafa Sahin

Primary Contact Information

Rajna Filip-Dhima, MS


For more information on this trial, visit


For more information and to contact the study team:

Natural History Study of Individuals With Autism and Germline Heterozygous PTEN Mutations NCT02461446 Rajna Filip-Dhima, MS 617-919-7068