Natural History With Focus on Oncological Risk Evaluation in Pediatric Patients With PTEN Pathogenic Variants
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: PTEN Hamartoma Syndrome. Basic parameters: up to 17 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Italy
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Natural History With Focus on Oncological Risk Evaluation in Pediatric Patients With PTEN Pathogenic Variants - Observational Study
Overview
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.
Primary outcome measures
- Rate of tumor onset in the pediatric subjects with PTEN pathogenic variants [Time frame: 5 years]
- Rate of tumor onset in the adult relatives of the pediatric subjects also carrying the PTEN pathogenic variant [Time frame: 5 years]
Secondary outcome measures (5)
- Rate of major malformations [Time frame: 5 years]
- Rate of incidence of brain MRI anomalies [Time frame: 5 years]
- Rate of incidence of neurological comorbidities [Time frame: 5 years]
- Rate of incidence of neurodevelopmental disorders [Time frame: 5 years]
- To analyze Head Circumferences and development of growth HC curves in PTEN patients (data of affected parents will be also recorded) [Time frame: 5 years]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Case-only
Study locations
Italy · 1 center
- Fondazione IRCCS Istituto Neurologico Carlo Besta — Milan
Publications
- Compton-Smith RN, Fawcett JW. Systemic lupus erythematosus associated with procainamide. Br J Clin Pract. 1967 May;21(5):248-51. No abstract available. PMID 6046409
- Chen CY, Chen J, He L, Stiles BL. PTEN: Tumor Suppressor and Metabolic Regulator. Front Endocrinol (Lausanne). 2018 Jul 9;9:338. doi: 10.3389/fendo.2018.00338. eCollection 2018. PMID 30038596
- Rademacher S, Eickholt BJ. PTEN in Autism and Neurodevelopmental Disorders. Cold Spring Harb Perspect Med. 2019 Nov 1;9(11):a036780. doi: 10.1101/cshperspect.a036780. PMID 31427284
Identifiers
NCT: NCT06805734 · PTEN_Ped