Neurodegeneration in an adolescent with Sjogren-Larsson syndrome: a decade-long follow-up case report

Kye Hee Cho, Sung Han Shim, Youngsoo Jung, Se Ra Sung, MinYoung Kim

Sjogren-Larsson syndrome is a hereditary neurocutaneous syndrome that is non-progressive in nature. Although neuroregression has been reported in seizure-prone preschool children requiring anti-epileptic treatment, teenage-onset dystonia precipitating neurodegeneration without any immediate causal events has yet to be reported. We describe a young woman with spastic diplegia and intellectual disability who began to show progressive neurological deterioration from 12 years of age, with the onset of dystonia and tremor. She was initially diagnosed with spastic cerebral palsy and periventricular leukomalacia based on brain magnetic resonance imaging. Follow-up brain imaging from 13 years of age did not reveal apparent changes, though abnormal electroencephalographic findings occurred in parallel with her decline in motor function. By 19 years of age, she had developed dysphagia and became completely dependent on others for most activities of daily living. Ultimately, whole-exome sequencing revealed a heterozygous compound mutation in the ALDH3A2 gene that corresponds to Sjogren-Larsson syndrome: an exon 9 deletion (1291-1292delAA) from the mother and an exon 5 splicing mutation (798 + 1delG) from the father. Neuroregression has been reported in preschool children after seizures requiring treatment, though our patient did not experience any immediate causal events. This report summarizes the clinical, radiologic, and electrophysiological findings observed over a decade concurrent with neurological deterioration after the onset of dystonia and tremor at the age of developmental ceiling in Sjogren-Larsson syndrome. In addition to the influence of additive variants or other environmental factors, accumulation of metabolites due to defective fatty aldehyde dehydrogenase is a potential pathomechanism of neurodegeneration in this patient. Neurological deterioration may be a presentation that is unnoticed in Sjogren-Larsson syndrome due to the rarity of the disease. This report highlights a unique clinical feature of Sjogren-Larsson syndrome with progressive neurodegeneration associated with dystonia and tremor.