PTEN Hamartoma Tumor Syndrome

NOTE: This is a research study and is not meant to be a substitute for clinical genetic testing. Families may never receive results from the study or may receive results many years from the time they enroll. If you are interested in clinical testing please consider seeing a local genetic counselor or other genetics professional. If you have already had clinical genetic testing and meet eligibility criteria for this study as shown in the Eligibility Section, you may enroll regardless of the results of your clinical genetic testing. While it is well recognized that hereditary factors contribute to the development of a subset of human cancers, the cause for many cancers remains unknown. The application of next generation sequencing (NGS) technologies has expanded knowledge in the field of hereditary cancer predisposition. Currently, more than 100 cancer predisposing genes have been identified, and it is now estimated that approximately 10% of all cancer patients have an underlying genetic predisposition. The purpose of this protocol is to identify novel cancer predisposing genes and/or genetic variants. For this study, the investigators will establish a Data Registry linked to a Repository of biological samples. Health information, blood samples and occasionally leftover tumor samples will be collected from individuals with familial cancer. The investigators will use NGS approaches to find changes in genes that may be important in the development of familial cancer. The information gained from this study may provide new and better ways to diagnose and care for people with hereditary cancer. PRIMARY OBJECTIVE: * Establish a registry of families with clustering of cancer in which clinical data are linked to a repository of cryopreserved blood cells, germline DNA, and tumor tissues from the proband and other family members. SECONDARY OBJECTIVE: * Identify novel cancer predisposing genes and/or genetic variants in families with clustering of cancer for which the underlying genetic basis is unknown.

The goal of this study is to examine the safety and treatment effects of everolimus in adults and children with PTEN Hamartoma Tumor Syndrome (PHTS) who experience social difficulties. The study will measure if everolimus can safely improve social abilities and functioning in this study population. PTEN Hamartoma Tumor Syndrome (PHTS) is a genetic condition that results from alteration (germline variant) to the PTEN gene. It is associated with a wide range of symptoms and characteristics, which vary from individual to individual. These include symptoms such as harmatomas (non-cancerous lesions), an increased risk of certain types of cancer, having a larger than average head, and abnormalities in blood vessels. Some people also have neurobehavioral problems including social difficulties. It is estimated approximately 25% (1 in 4) of people with PHTS meet the criteria for an autism diagnosis. The study lasts for one year. In the first 6 months half of participants will receive everolimus as a once daily oral tablet, and half will receive placebo tablets. For the second 6 months all participants will receive everolimus. Visits to the study clinic are required at the start, month 3, month 6, month 9 and month 12, with phone calls or virtual visits in between. Assessments include questionnaires, blood tests and urine tests, physical and neurological exams, and vital signs. Everolimus is an existing FDA approved medication used to treat other conditions, including a genetic condition called tuberous sclerosis complex which has some similarities to PHTS, and several types of cancer.

PtenTurkiye.org' is a national ( Turkish), web-based registry for PTEN Hamartoma Tumour ( PHTS) syndrome established in 2022. It is designed to increase awareness, gather scientific knowledge by collaboration and increase data accessibility, collect high-quality data on the epidemiology, genetic background and natural history of PHTS especially for pediatric patients so that more accurate follow up guidelines can be recommended.

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.