PTEN syndrome

PTEN syndrome is characterised by multiple hamartomas and a high chance of developing benign and malignant tumours of the thyroid, breast, endometrium and kidney. Affected individuals usually have macrocephaly and specific dermatological features, and may have neurodevelopmental delay.

Clinical features of PTEN syndrome include:

• macrocephaly (typically two standard deviations above the mean);
• pathognomonic mucocutaneous changes (facial trichilemmomas, acral keratoses and papillomatous ‘cobblestone-like’ lesions) as well as lipomas, vascular malformations and pigmented macule of the glans penis;
• benign and malignant tumours of the thyroid, breast, endometrium and kidney (the majority of cancerous presentations are in adulthood, though thyroid cancer has been reported in childhood);
• mixed bowel polyps, including hamartomatous, ganglioneuromatous, juvenile and adenomatous;
• developmental delay (particularly motor) and autistic spectrum disorders (overrepresented in this population); and
• adult-onset Lhermitte-Duclos disease (dysplastic gangliocytoma of the cerebellum, characteristic of PTEN-related conditions).

PTEN-related Proteus syndrome is a highly variable condition involving congenital malformations and hamartomatous overgrowth of multiple tissues.

The syndrome is caused by deletions or nonsense, missense and splicing variants in the PTEN gene (phosphatase and tensin homolog), a tumour suppressor gene located on the long arm of chromosome 10. PTEN negatively regulates the cytoplasmic receptor tyrosine kinase pathway, which is responsible for cell growth and survival, and also functions to repair errors in DNA.

For information about testing, see Presentation: Clinical suspicion of PTEN hamartoma tumour syndrome.

PTEN syndrome is an autosomal dominant condition, and the majority of cases are simplex. 10%–50% of affected individuals will have inherited the variant from their parents, except for those with PTEN-related Proteus syndrome, which almost always arises de novo. The offspring risk of an affected individual is 50%. If neither parent is found to carry the variant present in their affected child, the chance of recurrence for future pregnancies will be less than 1%.

Management of individuals with PTEN syndrome is based on the early detection and prevention of associated malignancies, principally from adulthood. Suggested approaches for managing children have been published by several authors – see our list of resources.

For clinicians

• GeneReviews: PTEN hamartoma tumor syndrome
• Genetic and Rare Diseases Information Center: PTEN hamartoma tumor syndrome
• Genomics England: NHS Genomic Medicine Service (GMS) Signed Off Panels Resource
• National Comprehensive Cancer Network
• NHS England: National Genomic Test Directory
• U.S. National Library of Medicine: ClinicalTrials.gov database

For patients

• Boston Children’s Hospital: PTEN hamartoma tumor syndrome (PHTS)
• The PTEN Foundation