Genotypic and Phenotypic Characteristics of Turkish Patients with Sjögren-Larsson Syndrome

Introduction: Sjögren-Larsson syndrome (SLS) (OMIM #270200) is an autosomal recessively inherited lipid disorder caused by pathogenic variants in ALDH3A2 gene encoding the fatty aldehyde dehydrogenase (FALDH) enzyme, that catalyzes the oxidation of fatty aldehyde to fatty acid. It is a rare neurocutaneous disorder characterized by the triad of congenital ichthyosis, spasticity and intellectual disability. The aim of study is to investigate phenotypic and molecular characteristics of Turkish patients with SLS. Methods: Literature search was performed by entering the keywords ALDH3A2, FALDH, Sjögren-Larsson syndrome in TR index journal list in Turkish and Pubmed in English. Turkish patients with SLS reported up to date were retrospectively analysed. Results: A total of 58 patients from 36 unrelated Turkish families were included in this study. Consanguinity was present in 73% of families. All but three patients younger than 18 months exhibited the triad of ichthyosis, developmental delay, and spastic di-/tetraplegia. Ophthalmological abnormalities were observed in 45% of patients, prematurity in 30%, epilepsy in 28%, and scoliosis in 17%. Additionally, only 2% of patients had peripheral neuropathy. Abnormal findings on brain imaging studies were detected in 84% of patients, all of whom demonstrated white matter involvement, while cerebral atrophy was present in 10%. All families had homozygous mutations, with missense in 45%, nonsense/frameshift/deletion in 35%, and splicing in 20%. Among the 15 distinct variants identified, only three, c.683G>A p.(Arg228His), c.24_25delinsTT p.(Arg9*), and c.1108-1G>C, were found to be recurrent. A review of the literature suggests that the c.24_25delinsTT p.(Arg9*) variant may be specific to the Turkish population, whereas the c.683G>A p.(Arg228His) variant appears to have a broader regional distribution across the Middle East. Conclusion: Although mild and severe phenotypes have been reported, the classical triad plays an important role in the preliminary diagnosis. Phenotypic findings were similar, but genotypic diversity was remarkable, and no clear genotype–phenotype correlation was observed. To make population-specific inferences, it is necessary to generate data from a larger patient cohort with haplotype analysis.