PTEN Hamartoma SyndromePTEN_PedNCT06805734
Natural History With Focus on Oncological Risk Evaluation in Pediatric Patients With PTEN Pathogenic Variants
An observational study of PTEN Hamartoma Syndrome, run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- PTEN Hamartoma Syndrome
- How many people
- 50 participants
- Where
- 1 siteItaly
- Study dates
- 1 Aug 2024to Jul 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 17 years
- All sexes
- No healthy volunteers
- Child
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
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS Istituto Neurologico Carlo Besta
Milan, 20133
Stefano D'Arrigo, MD, 02.2394.2210, stefano.darrigo@istituto-besta.it
Claudia Ciaccio, MD
About this study
Official title: Natural History With Focus on Oncological Risk Evaluation in Pediatric Patients With PTEN Pathogenic Variants - Observational Study
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.
Read the 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.
- Conditions
- PTEN Hamartoma Syndrome
- Keywords
- PTEN, PTHS
- Medical subject headings
- Hamartoma Syndrome, Multiple
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 5 years
Secondary outcomes (5)
Rate of major malformations
Children will be evaluated in order to exclude the presence of major malformations, including:
- heart malformations: a heart US would be also performed at diagnosis
- skin anomalies and global examination: a subcutaneous US will be performed if signs of possible peripheral vascular anomalies are present
- kidney and liver anomalies: those would be also assessed in the abdominal US already planned yearly
- limbs anomalies: in particular number of fingers/toes and limbs asymmetry
Measured: 5 years
Rate of incidence of brain MRI anomalies
All children will undergo a brain MRI to evaluate the presence or absence of cerebral anomalies
Measured: 5 years
Rate of incidence of neurological comorbidities
The presence or absence of possible neurological comorbidities will be investigated at diagnosis and at every clinical follow-up and data will be recorded in order to estimate the prevalence of the problem in the PTEN cohort.
Specifically, data about the following issues will be collected:
- epilepsy
- clinical neurological signs
- sleep disorder
- other neurological comorbidities.
Measured: 5 years
Rate of incidence of neurodevelopmental disorders
The presence or absence of neurodevelopmental diagnosis will be investigated at diagnosis, if not already assessed, and at every clinical follow-up and data will be recorded in order to estimate the prevalence of the problem in the PTEN cohort.
Global development and/or Intelligence Quotient level will be evaluated with standardized assessment tools, optimized for age and development. Griffiths Mental Development Scale - GMDS, Wechsler Preschool and Primary Scale of Intelligence - WPPSI, Wechsler Intelligence Scale for Children - WISC, and Leiter scales.
The presence of signs and symptoms of Autism Spectrum Disorder and other possible behavioral problems would also be assessed with standardized tools, both scales (Autism Diagnostic Observation Schedule - ADOS) and questionnaires (Child Behavior Checklist - CBCL, Social Responsiveness Scale - SRS, Adaptive Behavior Assessment System - ABAS).
Measured: 5 years
To analyze Head Circumferences and development of growth HC curves in PTEN patients (data of affected parents will be also recorded)
The HC measures will be monitored at diagnosis at at every follow-up visit in order to follow the head growth of the patients; data about the affected parents will also be recorded. To record data, WHO growth charts will be used as standardized charts.
Data will be used to develop a PTEN-specific head circumference growth chart.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2025
- Study start1 Aug 2024
- Primary completionJul 2029 (estimated)
- Study completionJul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for PTEN Hamartoma SyndromeStudies of the same condition, open and under way.
- More trials run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Azienda Ospedaliera Sant'Anna, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06805734
- Sponsor's protocol ID
- PTEN_Ped
- Acronym
- PTEN_Ped
- Status last verified
- Feb 2026
- First submitted
- 10 Dec 2024
- Last updated
- 12 Feb 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The participant centers in Italy will share data with the PI Institution. Study protocols and consent forms will be shared with the Institutions collaborating in the study in order to have omogeneous data record. Clinicians from the collaborative Centers will return anonymized data to the PI Institution.
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.
PubMed 6046409Chen 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.
PubMed 30038596Rademacher 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.
PubMed 31427284
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History With Focus on Oncological Risk Evaluation in Pediatric Patients With PTEN Pathogenic Variants - Observational Study
- ClinicalTrials.gov ID
- NCT06805734
- Acronym / sponsor ID
- PTEN_Ped / PTEN_Ped
- Conditions
- PTEN Hamartoma Syndrome
- Keywords
- PTEN, PTHS
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaUniversity, hospital or other
- Collaborators
- Azienda Ospedaliera Sant'Anna, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Study start
- 1 Aug 2024 (actual)
- Primary completion
- Jul 2029 (estimated)
- Study completion
- Jul 2029 (estimated)
- First posted
- 3 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- 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
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
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.
5 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2026.
- Background: PubMed 6046409Compton-Smith RN, Fawcett JW. Systemic lupus erythematosus associated with procainamide. Br J Clin Pract. 1967 May;21(5):248-51. No abstract available.
- Background: PubMed 30038596Chen 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.
- Background: PubMed 31427284Rademacher 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.
- Individual participant dataSharing planned: Yes. The participant centers in Italy will share data with the PI Institution. Study protocols and consent forms will be shared with the Institutions collaborating in the study in order to have omogeneous data record. Clinicians from the collaborative Centers will return anonymized data to the PI Institution.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Fondazione IRCCS Istituto Neurologico Carlo Besta
Milan, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of PTEN Hamartoma Syndrome, run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of tumor onset in the pediatric subjects with PTEN pathogenic variants (time frame: 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06805734, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2026.