A Neurodegenerative Phenotype Associated With Sjögren-Larsson Syndrome

Sjögren-Larsson syndrome (SLS) is a rare neurologic disorder caused by pathogenic sequence variants in ALDH3A2 and characterized by ichthyosis, spasticity, intellectual disability, and a crystalline retinopathy. Neurologic symptoms develop in the first 2 years of life. Except for worsening ambulation due to spastic diplegia and contractures, the neurologic disease has been considered static and a neurodegenerative course is distinctly unusual. We describe a young child with Sjögren-Larsson syndrome who exhibited an early and severely progressive neurologic phenotype that may have been triggered by a febrile rotavirus infection. Together with 7 additional published cases of these atypical patients, we emphasize that a neurodegenerative course can be an extreme outcome for a minority of patients with Sjögren-Larsson syndrome.