Natural History With Focus on Oncological Risk Evaluation in Pediatric Patients With PTEN Pathogenic Variants

NCT06805734 | Recruiting

• 1 other identifier: PTEN_Ped
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

PTEN Hamartoma Syndrome

Keywords

PTEN; PTHS

Outcome Measures

Primary Outcomes (2)

• Rate of tumor onset in the pediatric subjects with PTEN pathogenic variants

  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.

  5 years

• Rate of tumor onset in the adult relatives of the pediatric subjects also carrying the PTEN pathogenic variant

  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.

  5 years

Secondary Outcomes (5)

• 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

• To analyze Head Circumferences and development of growth HC curves in PTEN patients (data of affected parents will be also recorded)

  5 years

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: collaborator
• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta: lead
• Azienda Ospedaliera Sant'Anna: collaborator

Study Sites (1)

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, 20133, Italy

RECRUITING

Related Publications (3)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Hamartoma Syndrome, Multiple

Condition Hierarchy (Ancestors)

Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2024
• First Posted: February 3, 2025
• Study Start: August 1, 2024
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: 10 years, from August 1st 2024 to July 31st 2034
• Access Criteria: Data would be collected and recorded in encrypted Excel sheets with no name/surname/tax code shown; we ensure at each site the accuracy, completeness and timeliness of the files. Only the clinical personnel (medical doctors and neuropsychologists) involved in the study will have access to data, that could be accessed anytime but only from the Institutional Organizations participating in the study. Data will be stored at Carlo Besta Institute (SSD Sindromi Genetiche con Disabilità Intellettiva e Disturbi dello Spettro Autistico) for 10 years.

Locations

IT (1)