Sirolimus for Improving Social Abilities in People With PTEN Germline Mutations

Inclusion Criteria: * Inclusion Criteria: All participants will meet the following selection criteria: * Male or female outpatients between 5.00 and 45.99 years of age * PHTS confirmed by genetic testing; * Fluent in English * at least moderate severity of social skill deficits based on a social responsiveness scale t score ≥ 60 * Stable psychotropic and anti-epileptic medications for at least 4 weeks with the exception of fluoxetine which should be stable for at least 8 weeks * Adequate Liver function (SGOT, SGPT, TBili, Alk Phos all\<3x normal); HCT\>27%; WBC \> 3.0, ANC \>1,500, and platelets \>100,000 * adequate renal function with a GFR ≥ 50 ml/min/m2 as determined by the Schwartz Formula for children and MDRD for adults (www.nkdep.nih.gov/professionals/gfr\_calculators/index) * Negative urine pregnancy test for females and no plans to become pregnant or conceive a child while participating in the study. The effects of mTOR inhibitors on the developing fetus at the doses used in this study are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of the study. Because of the possibility of drug interactions and the potential effect of female hormones on the growth of kidney angiomyolipomas and lymphangioleiomyomatosis, estrogen-containing oral contraceptives are not recommended in women enrolled in this study, so an effective non-estrogen or barrier method of contraception must be used. * Medically stable with no active medical problems such as unstable seizures or cardiovascular disease or cancer that is not in remission as evidenced by medical history; -No anticipated changes in frequency and intensity of existing interventions such as behavioral and developmental treatments, in home services, or speech therapy; * No planned changes in school placement in children and adolescents; * Availability of reliable transportation to attend clinic visits; * availability of a trustworthy informant who interacts with subject on a regular basis; * Ability to participate in the testing procedures to the extent that valid standard scores and biological samples can be obtained. Exclusion Criteria: * Participants will be excluded if one of the following is met: * Significant medical illness, such as endocrinopathies, cardiovascular disease, or severe chronic malnutrition; * Pregnancy, planned pregnancy, or unwillingness to use adequate contraception; * Planned changes to concomitant medications; * Concomitant therapy, or prior use within 3 months of the baseline visit, with an agent with known or possible anti-mTOR activity or concomitant therapy with strong inhibitors (e.g., cyclosporine and ketoconazole) or inducers of CYP3A; * Active infection at time of enrollment; * Participation in a clinical trial in the 30 days prior to study entry; * Major surgery, radiation therapy or stereotactic radio-surgery within previous 4 weeks at time of enrollment; and * Neurosurgery within prior 6 months at time of enrollment.