Objective: The aim of this study was to provide a full characterization of a cohort of 11 pediatric patients diagnosed with PTEN hamartoma tumor syndrome (PHTS). Patients and methods: Eleven patients with genetic diagnostic of PHTS were recruited between February 2019 and April 2023. Clinical, imaging, demographic, and genetic data were retrospectively collected from their hospital medical history. Results: Regarding clinical manifestations, macrocephaly was the leading sign, present in all patients. Frontal bossing was the most frequent dysmorphism. Neurological issues were present in most patients. Dental malformations were described for the first time, being present in 27% of the patients. Brain MRI showed anomalies in 57% of the patients. No tumoral lesions were present at the time of the study. Regarding genetics, 72% of the alterations were in the tensin-type C2 domain of PTEN protein. We identified four PTEN genetic alterations for the first time. Conclusions: PTEN mutations appear with a wide variety of clinical signs and symptoms, sometimes associated with phenotypes which do not fit classical clinical diagnostic criteria for PHTS. We recommend carrying out a genetic study to establish an early diagnosis in children with significant macrocephaly. This facilitates personalized monitoring and enables anticipation of potential PHTS-related complications.

This study aims to analyze the diagnostic yield of aCGH in pediatric patients with suspected rare diseases, focusing on its diagnostic value and effectiveness depending on different clinical symptoms. This observational study analyzed 600 aCGH tests performed in a pediatric unit (2018-2022) for patients with suspected rare diseases. DNA was extracted from peripheral blood; aCGH resolution was adjusted to clinical features. CNVs were classified per international guidelines. Forty sociodemographic, clinical, and genetic variables were analyzed using IBM SPSS v.26. Of the 600 patients analyzed, 543 were included in the final study. The median age was 4.7 years (IQR: 6.36 years), and 66.3% were male. Most referrals came from pediatric neurology (84.3%), and the most common clinical manifestations were altered phenotype (38.6%), autism spectrum disorder (ASD) (38.6%), dysmorphia (28.2%), global developmental delay (GDD) (27.1%), and intellectual disability (21.0%). Among 543 patients, 30.4% presented CNVs, with 12.4% identified as pathogenic and 18.1% as variants of uncertain significance. Diagnostic yield was 12.2%, with 66 conclusive results - 90.9% of which were pathogenic. CNVs were most frequently detected on chromosomes 15 and 16. The highest yield was observed in clinical features such as coordination problems (35.7%), learning disorders (28.6%), and microcephaly (22.6%). The diagnostic yield of aCGH in this study was 12.2%. The test demonstrated higher diagnostic value in patients with multiple clinical manifestations, highlighting the importance of aCGH as a first-line diagnostic tool for rare diseases. This technique enables earlier diagnosis, improves clinical management, and provides better counseling for affected families.