Clinical trial NCT06805734: Natural History With Focus on Oncological Risk Evaluation in Pediatric Patients With PTEN Pathogenic Variants - Observational Study
Official title: Natural History With Focus on Oncological Risk Evaluation in Pediatric Patients With PTEN Pathogenic Variants - Observational Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: PTEN Hamartoma Syndrome
Keywords: PTEN
PTHS
Lead sponsor: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
Sponsor class: OTHER
Collaborators: name: Azienda Ospedaliera, Ospedale Sant'Anna-Como
name: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
First posted: 2025-02-03
Enrollment: 50
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pediatric patients (\<18 years of age at enrollment) with pathogenic variants of PTEN genes (gene sequence variant, intragenic deletion/duplication, whole gene deletion) Carrier parents data would also be collected

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.

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

Primary outcomes:
measure: Rate of tumor onset in the pediatric subjects with PTEN pathogenic variants
timeFrame: 5 years
measure: Rate of tumor onset in the adult relatives of the pediatric subjects also carrying the PTEN pathogenic variant
timeFrame: 5 years
Secondary outcomes:
measure: Rate of major malformations
timeFrame: 5 years
measure: Rate of incidence of brain MRI anomalies
timeFrame: 5 years
measure: Rate of incidence of neurological comorbidities
timeFrame: 5 years
measure: Rate of incidence of neurodevelopmental disorders
timeFrame: 5 years
measure: To analyze Head Circumferences and development of growth HC curves in PTEN patients (data of affected parents will be also recorded)
timeFrame: 5 years
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta
Study officials:
References:
citation: Compton-Smith RN, Fawcett JW. Systemic lupus erythematosus associated with procainamide. Br J Clin Pract. 1967 May;21(5):248-51. No abstract available.
citation: 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.
citation: 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.