Catch them if you are aware: PTEN postzygotic mosaicism in clinically suspicious patients with PTEN Hamartoma Tumour Syndrome and literature review

Eur J Med Genet. 2022 Jul;65(7):104533. doi: 10.1016/j.ejmg.2022.104533. Epub 2022 May 28.


PTEN germline variants cause PTEN Hamartoma Tumour Syndrome (PHTS). Of individuals fulfilling diagnostic criteria, 41-88% test negative for PTEN germline variants, while mosaicism could be an explanation. Here we describe two individuals with PTEN mosaicism. First, a 21-year-old female presented with macrocephaly and a venous malformation. Next generation sequencing analysis on her venous malformation identified the mosaic pathogenic PTEN variant c.493-2A>G (23%). This variant was initially missed in blood due to low frequency (<1%), but detected in buccal swab (21%). Second, a 13-year-old male presented with macrocephaly, language developmental delay, behavioral problems, and an acral hyperkeratotic papule. Targeted PTEN analysis identified the mosaic pathogenic variant c.284C>T (11%) in blood, which was confirmed via buccal swab. These two cases suggest that PTEN mosaicism might be more common than currently reported. PTEN mosaicism awareness is important to enable diagnosis, which facilitates timely inclusion in cancer surveillance programs improving prognosis and life expectancy.

Keywords: Cowden syndrome; Hamartoma syndrome, Multiple; Mosaicism; PTEN.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Developmental Disabilities
  • Female
  • Hamartoma Syndrome, Multiple* / diagnosis
  • Hamartoma Syndrome, Multiple* / genetics
  • Hamartoma Syndrome, Multiple* / pathology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Megalencephaly*
  • Mosaicism
  • PTEN Phosphohydrolase / genetics
  • Young Adult


  • PTEN Phosphohydrolase
  • PTEN protein, human