Broad spectrum of neuropsychiatric phenotypes associated with white matter disease in PTEN hamartoma tumor syndrome

Am J Med Genet B Neuropsychiatr Genet. 2018 Jan;177(1):101-109. doi: 10.1002/ajmg.b.32610. Epub 2017 Nov 20.

Abstract

White matter lesions have been described in patients with PTEN hamartoma tumor syndrome (PHTS). How these lesions correlate with the neurocognitive features associated with PTEN mutations, such as autism spectrum disorder (ASD) or developmental delay, has not been well established. We report nine patients with PTEN mutations and white matter changes on brain magnetic resonance imaging (MRI), eight of whom were referred for reasons other than developmental delay or ASD. Their clinical presentations ranged from asymptomatic macrocephaly with normal development/intellect, to obsessive compulsive disorder, and debilitating neurological disease. To our knowledge, this report constitutes the first detailed description of PTEN-related white matter changes in adult patients and in children with normal development and intelligence. We present a detailed assessment of the neuropsychological phenotype of our patients and discuss the relationship between the wide array of neuropsychiatric features and observed white matter findings in the context of these individuals.

Keywords: PTEN; PTEN hamartoma tumor syndrome; white matter disease.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Autism Spectrum Disorder / genetics
  • Child
  • Child, Preschool
  • Developmental Disabilities
  • Female
  • Hamartoma Syndrome, Multiple / genetics
  • Hamartoma Syndrome, Multiple / physiopathology*
  • Humans
  • Intelligence
  • Leukoencephalopathies / genetics
  • Leukoencephalopathies / metabolism*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • PTEN Phosphohydrolase / metabolism*
  • Phenotype
  • White Matter / pathology

Substances

  • PTEN Phosphohydrolase
  • PTEN protein, human