Genotype and phenotype variability in Sjögren-Larsson syndrome

Maximilian Weustenfeld, Reiner Eidelpes, Matthias Schmuth, William B. Rizzo, Johannes Zschocke, Markus A. Keller

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


The Sjögren–Larsson syndrome (SLS) is a rare autosomal recessive disorder caused by pathogenic variants in the ALDH3A2 gene, which codes for fatty aldehyde dehydrogenase (FALDH). FALDH prevents the accumulation of toxic fatty aldehydes by converting them into fatty acids. Pathogenic ALDH3A2 variants cause symptoms such as ichthyosis, spasticity, intellectual disability, and a wide range of less common clinical features. Interpreting patient-to-patient variability is often complicated by inconsistent reporting and negatively impacts on establishing robust criteria to measure the success of SLS treatments. Thus, with this study, patient-centered literature data was merged into a concise genotype-based, open-access database ( One hundred and seventy eight individuals with 90 unique SLS-causing variants were included with phenotypic data being available for more than 90%. While the three lead symptoms did occur in almost all cases, more heterogeneity was observed for other frequent clinical manifestations of SLS. However, a stringent genotype–phenotype correlation analysis was hampered by the considerable variability in reporting phenotypic features. Consequently, we compiled a set of recommendations of how to generate comprehensive SLS patient descriptions in the future. This will be of benefit on multiple levels, for example, in clinical diagnosis, basic research, and the development of novel treatment options for SLS.

Original languageEnglish (US)
Pages (from-to)177-186
Number of pages10
JournalHuman mutation
Issue number2
StatePublished - Feb 2019


  • ALDH3A2
  • SLS
  • Sjögren–Larsson syndrome
  • database
  • fatty aldehyde dehydrogenase

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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