Natural History With Focus on Oncological Risk Evaluation in Pediatric Patients With PTEN Pathogenic Variants - Observational Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Rate of tumor onset in the adult relatives of the pediatric subjects also carrying the PTEN pathogenic variant
Study Overview
Brief Summary
This is an observational study in pediatric patientis carryng PTEN pathogenic variants aimed to define oncological risk in children and provide a deeper insight of the clinical course, establishing an updated follow-up protocol.
Detailed Description
PTEN is a tumor suppressor gene that was first linked to cancer predisposition syndromes but, in the following years, its phenotypic spectrum has been in continuous evolution and expansion, and nowadays we know that pathogenic variants n this gene may also be found in children presenting with Autism Spectrum Disorder (ASD), and/or DD and macrocephaly, or also with macrocephaly alone. Thus, the term PTEN Hamartoma Tumor Syndrome (PTHS) is now used when referring to PTEN-related conditions.
Nowadays, there is no recognized standard protocol for pediatric follow-up. The screening in mostly single-Centre-based and generally not performed in infancy, with large variability in protocols and timing.
The penetrance, which was previously believed to follow an age-related pattern, nowadays seems rather to be age-specific, as children mainly present macrocephaly and neuropsychiatric problems (DD/ASD), while adults are diagnosed mostly because of gastrointestinal malignancies, breast cancer, thyroid carcinoma or other tumors. However, it is not always true that adult symptoms never occur in PTHS children and, conversely, pediatric signs may also persist through adulthood.
The present study aims to collect PTEN mutated patients and their relatives diagnosed in Italy and followed in different Centers, offering a large pediatric cohort with a full clinical description and trying to provide a deeper insight of the clinical course and oncological manifestations of PTEN-related syndrome; we would like to establish an updated follow-up protocol in order to address all the possible clinical needs of these children.
Study Design
- Study Type
- Observational
- Observational Model
- Case Only
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- — to 17 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •PTEN pathogenic variants (class 4/5 SNV, gene deletion, intragenic duplication/deletion)
- •Pediatric patients (<18 years old) and their affected relatives, male/female, all ethnicities
- •The legal representative must agree to follow the screening protocol
- •Informed consent signed by the legal representative
Exclusion Criteria
- •Refuse to undergo the exams of the protocol assessment at the diagnosis
- •PTEN non-pathogenic variants (VOUS or benign/likely benign vatiants)
- •No signed informed consent
Outcomes
Primary Outcomes
Rate of tumor onset in the adult relatives of the pediatric subjects also carrying the PTEN pathogenic variant
Time Frame: 5 years
The oncological risk of tumor onset in the pediatric cohort will be compared with that of relatives carrying pathogenic variants. Pediatric patients will undergo annual follow-up for the 5 years of the study. Within the same time frame, adult relatives of the index case carrying the same PTEN variant will also be monitored in order to compare oncological risk in adult and pediatric populations and to evaluate phenotypic differences across different stages of life.
Rate of tumor onset in the pediatric subjects with PTEN pathogenic variants
Time Frame: 5 years
In the 5 years follow-up the subjects must complete annually the provided follow-up. Most of the exams are performed in order to exclude the onset of PTEN-related tumors, in particular: * blood tests: thyroid function, renal function, hepatic function, blood count cell exam: screening for thyroid, kidney, liver and intestinal tumors * fecal occult blood (FOB): screening for colorectal cancer and polyps * dermatological evaluation (at the diagnosis, further evaluations if clinically needed) * thyroid US: screening for thyroid tumors * abdominal US: screening for kidney, liver and intestinal tumors * clinical follow-up (performed either by a geneticist, a pediatrician or a pediatric neurologist): exams evaluation and global monitoring. The oncological risk of the patients would be estimated basing on the number of patients who will develop a tumor, benign or malignant, in the 5-years follow-up.
Secondary Outcomes
- To analyze Head Circumferences and development of growth HC curves in PTEN patients (data of affected parents will be also recorded)(5 years)
- Rate of major malformations(5 years)
- Rate of incidence of brain MRI anomalies(5 years)
- Rate of incidence of neurological comorbidities(5 years)
- Rate of incidence of neurodevelopmental disorders(5 years)