Endocrine Abstracts

Background: PTEN hamartoma tumour syndromes (PHTS) are rare autosomal dominant inherited disorders characterised by macrocephaly, multiple hamartomas and an increased risk of several cancers, including breast, thyroid and endometrium. PTEN encodes a tumour suppressor phosphatase that regulates cell survival and migration. Published guidelines are available for adult patients but screening in children is currently not standardised. Moreover, there is poor genotype-phenotype correlation and age-related penetrance in PTEN mutations, making decisions around appropriate paediatric surveillance highly complex.

Aim: To examine the literature for existing guidelines and epidemiological data to produce a comprehensive screening plan for our paediatric PHTS patients.

Patients and methods: We manage two siblings with a confirmed germline truncating mutation in PTEN (R233X) inherited from their mother, who developed Hashimoto’s thyroiditis and a compressing thyroid goitre requiring near-total thyroidectomy aged 28 years. Both children have macrocephaly and developmental delay with autistic-spectrum features but are otherwise asymptomatic (aged 7 and 6 years). A primary search of Medline via PubMed and secondary searches via national guideline databases were carried out.

Results: 12 relevant papers and two published guidelines (NICE guidelines, National Comprehensive Cancer Network guidelines) were identified. The risk for tumour development in patients with PTEN mutations is considered low in childhood, and no screening guidelines were found for paediatric patients. Surveillance is recommended from 18 years unless there is a family history of cancer <23 years. However, a recent case series reported the development of thyroid nodules and cancer from early childhood.

Conclusions: Available guidance for the management in childhood of PHTS patients is limited. The lack of paediatric reports of PHTS-associated cancer may be explained by previous diagnostic limitations. We recommend yearly physical examination (particularly of skin and thyroid) and yearly thyroid ultrasound upon diagnosis. In view of the high lifetime risk of malignancy it is important to keep patients under close surveillance.