Novel PTEN germline mutation in a family with mild phenotype: difficulties in genetic counseling

Gene. 2013 Jan 10;512(2):194-7. doi: 10.1016/j.gene.2012.09.134. Epub 2012 Nov 2.


PTEN gene (phosphatase and tensin homolog deleted on chromosome ten, MIM 601628) is a tumor suppressor gene implicated in PTEN hamartoma tumor syndromes (PHTS) including Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome and Proteus-like syndrome. PTEN mutations have been more recently reported in children with macrocephaly and autism spectrum disorders or mental retardation, without other symptoms of PHTS. Although tumor risk has not been evaluated in these patients and their relatives, the same surveillance as for Cowden syndrome is usually proposed. We report a family including patients carrying a novel PTEN mutation and presenting with a mild phenotype consisting of macrocephaly, hypotonia during the first year of life and mild learning disabilities, without autistic features. None of these patients exhibited PTHS-related symptoms such as tumors, lipomas, vascular malformations or pigmented macules of the glans penis. This report raises the question of extending the indications of PTEN mutation screening to familial macrocephaly with learning disabilities. Detection of a mutation in this family led to difficult questions about surveillance, genetic counseling and familial information since the mother declined tumor screening and disclosure of genetic risk information to at-risk relatives.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Family*
  • Female
  • Genetic Counseling*
  • Germ-Line Mutation*
  • Hamartoma Syndrome, Multiple / diagnosis
  • Hamartoma Syndrome, Multiple / genetics
  • Hamartoma Syndrome, Multiple / pathology
  • Humans
  • Male
  • Megalencephaly / diagnosis
  • Megalencephaly / genetics
  • Megalencephaly / pathology
  • Muscle Hypotonia / diagnosis
  • Muscle Hypotonia / genetics
  • Muscle Hypotonia / pathology
  • PTEN Phosphohydrolase / genetics*
  • Risk Factors


  • PTEN Phosphohydrolase
  • PTEN protein, human