Adult Hereditary White Matter Diseases With Psychiatric Presentation: Clinical Pointers and MRI Algorithm to Guide the Diagnostic Process

J Neuropsychiatry Clin Neurosci. 2021 Summer;33(3):180-193. doi: 10.1176/appi.neuropsych.20110294. Epub 2021 May 6.


Objective: The investigators aimed to provide clinical and MRI guidelines for determining when genetic workup should be considered in order to exclude hereditary leukoencephalopathies in affected patients with a psychiatric presentation.

Methods: A systematic literature review was conducted, and clinical cases are provided. Given the central role of MRI pattern recognition in the diagnosis of white matter disorders, the investigators adapted an MRI algorithm that guides the interpretation of MRI findings and thus directs further investigations, such as genetic testing.

Results: Twelve genetic leukoencephalopathies that can present with psychiatric symptoms were identified. As examples of presentations that can occur in clinical practice, five clinical vignettes from patients assessed at a referral center for adult genetic leukoencephalopathies are provided.

Conclusions: Features such as drug-resistant symptoms, presence of long-standing somatic features, trigger events, consanguinity, and positive family history should orient the clinician toward diagnostic workup to exclude the presence of a genetic white matter disorder. The identification of MRI white matter abnormalities, especially when presenting a specific pattern of involvement, should prompt genetic testing for known forms of genetic leukoencephalopathies.

Keywords: Adult-Onset Leukoencephalopathies; Leukodystrophies; Leukoencephalopathies; Neurogenetics; Psychiatric-Onset.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Age of Onset
  • Algorithms*
  • Brain / pathology
  • Female
  • Guidelines as Topic*
  • Humans
  • Leukoencephalopathies* / diagnostic imaging
  • Leukoencephalopathies* / genetics
  • Leukoencephalopathies* / pathology
  • Magnetic Resonance Imaging*
  • Male
  • Mental Disorders / diagnosis*
  • Middle Aged