Clinical spectrum of PTEN mutation in pediatric patients. A bicenter experience

Claudia Ciaccio, Veronica Saletti, Stefano D'Arrigo, Silvia Esposito, Enrico Alfei, Isabella Moroni, Davide Tonduti, Luisa Chiapparini, Chiara Pantaleoni, Donatella Milani

Research output: Contribution to journalArticlepeer-review


Objective of the study: To give a full overview of the clinical presentation of PTEN mutations in pediatric patients and to propose a pediatric follow-up protocol. Methods: Recruitment of 16 PTEN mutated children (age 6 months-11 years) from two pediatric centers in Milan (Italy) between 2006 and 2017. All the patients underwent clinical and neurologic evaluations, cognitive and behavioral tests, and brain MRI; they are currently following an oncologic follow-up. Results: Extreme macrocephaly is present in all the patients (69% HC above +4 SD). Neuropsychiatric issues have high prevalence, with 56% of patients showing developmental delay and 25% showing autism spectrum disorder. Brain MRI reveals in 75% of the patients at least one of the following: enlarged perivascular spaces, white matter anomalies, and/or downward displacement of the cerebellar tonsils through the foramen magnum, resulting in Chiari I malformation in two patients. Vascular malformations have a prevalence of 19%, with further evidence that complex cardiovascular malformations may be related to PTEN mutations; 31% of patients present hamartomas. None of our patients have so far experienced any oncologic complication. Conclusions: We suggest to screen for PTEN mutations all children presenting macrocephaly and one of the following: neurodevelopmental issues, one of the three major brain MRI anomalies, cutaneous lesions, vascular malformations, family history positive for PTEN related malignancies; or also with macrocephaly alone when exceeding +3 SD. Basing on our cohort results and further recent studies on the condition, we recommend a follow-up protocol that includes annual clinical and dermatological examination, thyroid and abdominal US, and Fecal Occult Blood test plus neurodevelopmental evaluation, heart US (to exclude congenital heart malformations), and brain MRI (to exclude Chiari I malformation) at diagnosis.

Original languageEnglish
Article number103596
JournalEuropean Journal of Medical Genetics
Issue number12
Publication statusPublished - 2019


  • Chiari I malformation
  • Dysmorphology
  • Neurodevelopmental disorders
  • Pediatric oncology
  • PTEN

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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