PTEN Hamartoma tumor syndrome in childhood: A review of the clinical literature

Abstract

PTEN hamartoma tumor syndrome (PHTS) is a highly variable autosomal dominant condition associated with intellectual disability, overgrowth, and tumor predisposition phenotypes, which often overlap. PHTS incorporates a number of historical clinical presentations including Bannayan‐Riley‐Ruvalcaba syndrome, Cowden syndrome, and a macrocephaly‐autism/developmental delay syndrome. Many reviews in the literature focus on PHTS as an adult hamartoma and malignancy predisposition condition. Here, we review the current literature with a focus on pediatric presentations. The review starts with a summary of the main conditions encompassed within PHTS. We then discuss PHTS diagnostic criteria, and clinical features. We briefly address rarer PTEN associations, and the possible role of mTOR inhibitors in treatment. We acknowledge the limited understanding of the natural history of childhood‐onset PHTS as a cancer predisposition syndrome and present a summary of important management considerations.

Cancer Surveillance Guideline for individuals with PTEN hamartoma tumour syndrome

“…For individuals that meet the diagnostic criteria for PHTS, but where no PV has been identified, surveillance should be tailored on a case by case base, taking into account the personal and family history of cancer. PHTS-related cancers are predominately adult onset and no specific recommendations have been made for non-malignant manifestations in adults or for the paediatric PHTS population whose management has been addressed elsewhere [ 17 ].…”

Cutaneous lipomas and macrocephaly as early signs of PTEN hamartoma tumor syndrome

“…These two genetic syndromes are characterized by a phosphatase and tensin homologue ( PTEN ) gene mutation and are now unified into the single entity, PTEN hamartoma tumor syndrome (PHTS) 4 . Macrocephaly with developmental delay (DD), intellectual disability (ID), or autism spectrum disorder (ASD) are the most common presenting signs in childhood, but dermatological findings are often present at diagnosis 5‐7 …”

Characterization and Childhood Tumor Risk Assessment of Genetic and Epigenetic Syndromes Associated With Lateralized Overgrowth

“…PHTS is the umbrella term for genetic syndromes caused by germline PTEN mutations. Common clinical features of pediatric patients with PHTS include macrocephaly, hamartomas, lipomas, cardiac defects, and autism (66). LO is due to adipose and vascular anomalies.…”

“…Major and minor criteria were implemented to aid in diagnosis. Major criteria include the presence of macrocephaly, macular pigmentation of the glans penis, and multiple mucocutaneous lesions, and minor criteria include autism, lipomas, and vascular malformations (66,67).…”