General description

Sjögren-Larsson syndrome (SLS) is a rare autosomal recessive neurocutaneous disorder characterized by a triad of congenital ichthyosis, intellectual disability, and spastic diplegia or tetraplegia. Sjögren-Larsson syndrome is caused by mutations in the ALDH3A2 gene located on chromosome 17p11.2, which encodes fatty aldehyde dehydrogenase (FALDH). FALDH is a microsomal enzyme that catalyzes the oxidation of medium and long-chain aliphatic aldehydes derived from various sources including fatty alcohol, phytanic acid, ether glycerolipids, and sphingolipids to fatty acids. The deficiency of this enzyme results in the accumulation of fatty aldehydes and alcohols in various tissues, particularly affecting the skin, nervous system, and eyes.

Preterm birth is frequently observed in patients with SLS. At or shortly after birth, these individuals typically show skin abnormalities consistent with ichthyosis. The skin initially appears red and thickened, gradually becoming dry and scaly. This condition usually affects most of the body but tends to spare the central face and is especially prominent in certain body folds.

Neurological symptoms generally begin in early childhood, with delayed motor development caused by spasticity, particularly in the legs. Most patients eventually require wheelchairs, although some can walk with assistance. Cognitive abilities are usually moderately impaired, with developmental age plateauing at around five to six years. Despite these limitations, cognitive function remains stable through early adulthood. Speech difficulties are also common, often due to pseudobulbar dysarthria, and are associated with impaired orofacial motor function. While motor and speech impairments do not directly correlate, there is a link between cognitive and language development.

Magnetic Resonance Spectroscopy

MRS of the brain in SLS patients reveals a characteristic abnormal lipid peak at 1.3 ppm and a small peak at 0.9 ppm. This finding is considered highly specific for SLS.

References

1. Bindu, Parayil Sankaran. "Sjogren-Larsson syndrome: mechanisms and management." The Application of Clinical Genetics (2020): 13-24.