Sjögren-Larsson syndrome

Sjögren-Larsson syndrome (SLS) is a rare inherited neurocutaneous disorder characterized by the triad of ichthyosis (thickened, scaly skin), spastic diplegia or tetraplegia, and intellectual disability. The condition was first described by Sjögren and Larsson in 1957 in a Swedish population. It is caused by mutations in the ALDH3A2 gene, which encodes fatty aldehyde dehydrogenase (FALDH), an enzyme critical for the oxidation of long-chain fatty aldehydes. Deficiency of this enzyme leads to accumulation of fatty aldehydes and fatty alcohols in tissues, particularly affecting the skin and central nervous system. Ichthyosis is typically present at birth or develops within the first few months of life, often initially appearing as a generalized redness (erythroderma) that evolves into dark, lamellar-type scaling, most prominent on the trunk, extremities, and flexural areas. Neurological symptoms become apparent during the first two years of life, with progressive spasticity predominantly affecting the lower limbs (spastic diplegia), though all four limbs may be involved. Intellectual disability ranges from mild to severe. A distinctive ophthalmological finding is the presence of glistening white dots (crystalline macular dystrophy) on the retina, which can be detected by fundoscopy and is highly characteristic of SLS. Seizures occur in approximately 40% of affected individuals. Brain MRI often shows white matter abnormalities, and magnetic resonance spectroscopy may reveal an abnormal lipid peak. There is currently no cure for Sjögren-Larsson syndrome, and treatment is primarily supportive and symptomatic. Skin management includes emollients, keratolytic agents, and topical retinoids to reduce scaling. Spasticity may be managed with physical therapy, orthopedic interventions, botulinum toxin injections, or oral antispasticity medications such as baclofen. Seizures are treated with standard antiepileptic drugs. Zileuton, a 5-lipoxygenase inhibitor, has been investigated as a potential therapy to reduce leukotriene B4 levels, which are elevated in SLS, with some reports of modest improvement in pruritus and skin symptoms. Early intervention programs, speech therapy, and special education support are important for optimizing developmental outcomes.

Common questions about Sjögren-Larsson syndrome