Clinical, biochemical, and genetic aspects of Sjögren-Larsson syndrome

Clin Genet. 2018 Apr;93(4):721-730. doi: 10.1111/cge.13058. Epub 2017 Sep 17.

Abstract

Sjögren-Larsson syndrome (SLS) is caused by an autosomal recessive mutation in ALDH3A2, which encodes the fatty aldehyde dehydrogenase responsible for the metabolism of long-chain aliphatic aldehydes and alcohols. The pathophysiologic accumulation of aldehydes in various organs, including the skin, brain, and eyes, leads to characteristic features of ichthyosis, intellectual disability, spastic di-/quadriplegia, and low visual acuity with photophobia. The severity of the clinical manifestations thereof can vary greatly, although most patients are bound to a wheelchair due to contractures. To date, correlations between genotype and phenotype have proven difficult to document due to low disease incidence and high heterogenetic variability in mutations. This review summarizes the clinical characteristics of SLS that have been found to contribute to the prognosis thereof, as well as recent updates from genetic and brain imaging studies. In addition, the differential diagnoses of SLS are briefly illustrated, covering cerebral palsy and other genetic or neurocutaneous syndromes mimicking the syndrome.

Keywords: FALDH deficiency; genetic variations; ichthyosis; intellectual disability; macular dystrophy; neurocutaneous disease; spastic diplegia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aldehyde Oxidoreductases / genetics
  • Brain / metabolism*
  • Brain / pathology
  • Cerebral Palsy / diagnosis
  • Cerebral Palsy / genetics*
  • Cerebral Palsy / pathology
  • Humans
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Mutation
  • Phenotype
  • Photophobia / genetics
  • Photophobia / physiopathology
  • Sjogren-Larsson Syndrome / diagnosis
  • Sjogren-Larsson Syndrome / genetics*
  • Sjogren-Larsson Syndrome / pathology
  • Skin
  • Visual Acuity / genetics
  • Visual Acuity / physiology

Substances

  • Aldehyde Oxidoreductases
  • long-chain-aldehyde dehydrogenase