PTEN Hamartoma Syndrome
Conditions
Keywords
PTEN, PTHS
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.
Interventions
None listed
Sponsors
Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
Azienda Ospedaliera Sant'Anna
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of tumor onset in the pediatric subjects with PTEN pathogenic variants | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of major malformations | 5 years | 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 |
| Rate of incidence of brain MRI anomalies | 5 years | All children will undergo a brain MRI to evaluate the presence or absence of cerebral anomalies |
| Rate of incidence of neurological comorbidities | 5 years | 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. |
| Rate of incidence of neurodevelopmental disorders | 5 years | 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). |
| To analyze Head Circumferences and development of growth HC curves in PTEN patients (data of affected parents will be also recorded) | 5 years | 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. |
Countries
Italy
Outcome results
None listed