Natural History Study of Individuals With Autism and Germline Heterozygous PTEN Mutations

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 (ages 3 to 21), 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. 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 5 visits (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 and neuropsychological assessments and a blood draw done for
laboratory studies. Individuals who have a clinically indicated MRI will have their scan
extended for 15 minutes as part of this study.

Inclusion Criteria:

- Individuals ages 3 to 21 years old at the time of consent who have documentation of a
clinical diagnosis of autism spectrum disorder diagnosis 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.

- Youth ages 3-17 and adults age 18-21 who do not have an autism spectrum disorder or a
PTEN mutation for inclusion in the control group.

- Consent from parents or guardians or an adult with or suspected of having an autism
spectrum disorder that does not require a legal guardian or an adult who is the
healthy sibling of an individual with an autism spectrum disorder.

- Youths who are able (some young or severely impaired participants may not be able to
provide assent) will be asked to provide assent.

- 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:

- Clinically significant medical disease that would prohibit participation in the study
procedures.

- Individuals with contraindication to MRI will be excluded from the MRI portion of the
study such as:

1. Cardiac pacemaker.

2. Intracranial aneurysm clips, metallic implants or external clips within 10 mm of
the head.

3. Implanted metallic devices such as pumps or neuro-stimulator devices.

4. Metallic foreign material within the orbits.

5. Pregnancy.

6. Claustrophobia.

- No history of significant brain lesions or pathology including:

1. History of large vessel strokes, brain tumors or previous neurosurgery.