The spectrum of vascular anomalies in patients with PTEN mutations: implications for diagnosis and management

J Med Genet. 2007 Sep;44(9):594-602. doi: 10.1136/jmg.2007.048934. Epub 2007 May 25.

Abstract

Background: Mutations in the PTEN gene cause two disorders that predispose to cancer, Bannayan-Riley-Ruvalcaba and Cowden syndromes. Some patients with a PTEN mutation have only macrocephaly and autism, but they may still be at risk for neoplasms. Vascular anomalies occur in patients with a PTEN mutation, but they have not been systematically studied or precisely defined.

Method: We analysed the clinical and radiological features of the vascular anomalies in 26 patients with PTEN mutations who were either seen or had their medical records reviewed at Children's Hospital Boston.

Results: All 23 patients who had their head circumference measured were macrocephalic, and all 13 male patients who were fully examined had penile freckling. Vascular anomalies were found in 14/26 (54%) of patients: 8/14 (57%) had multiple lesions and 11/13 (85%) who had cross-sectional imaging had intramuscular vascular lesions. Radiographic studies showed that 12/14 (86%) were fast-flow vascular anomalies, and angiography typically showed focal segmental dilatation of draining veins. Excessive ectopic fat in the vascular anomalies was present in 11/12 (92%) of patients on CT or MRI. Intracranial developmental venous anomalies (DVAs) were found in 8/9 (89%) of patients who had brain MRI with contrast.

Conclusions: Vascular anomalies in patients with a PTEN mutation are typically multifocal intramuscular combinations of fast-flow channels and ectopic fat. Cerebral DVAs are very common. PTEN mutational analysis should be considered for all macrocephalic patients with fast-flow vascular anomalies or multiple intracranial DVAs.

Publication types

  • Letter

MeSH terms

  • Adipose Tissue / pathology
  • Adolescent
  • Arteriovenous Fistula / classification
  • Arteriovenous Fistula / genetics*
  • Arteriovenous Fistula / pathology
  • Blood Flow Velocity
  • Blood Vessels / abnormalities*
  • Case Management
  • Child
  • Child, Preschool
  • Female
  • Hamartoma Syndrome, Multiple / genetics*
  • Head / abnormalities
  • Hemangioma / genetics
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Melanosis / genetics
  • Middle Aged
  • Mutation
  • PTEN Phosphohydrolase / genetics*
  • Phenotype
  • Retrospective Studies

Substances

  • PTEN Phosphohydrolase
  • PTEN protein, human