Expanding the Natural History of SNORD118-Related Ribosomopathy: Hints from an Early-Diagnosed Patient with Leukoencephalopathy with Calcifications and Cysts and Overview of the Literature

Abstract

Leukoencephalopathy with calcifications and cysts (LCC) is a rare autosomal recessive disorder showing a pediatric or adult onset. First described in 1996 by Labrune and colleagues, it was only in 2016 that bi-allelic variants in a non-protein coding gene, SNORD118, were found as the cause for LCC, differentiating this syndrome from coats plus (CP). SNORD118 transcribes for a small nucleolar RNA, which is necessary for correct ribosome biogenesis, hence the classification of LCC among ribosomopathies. The syndrome is characterized by a combination of white matter hyperintensities, calcifications, and cysts on brain MRI with varying neurological signs. Corticosteroids, surgery, and recently bevacizumab, have been tried with unclear results since the natural history of the disease remains elusive. To date, 67 patients with a pediatric onset of disease have been described in the literature, with a clinical-radiological follow-up carried out in only eleven of them. We described the clinical-radiological follow-up from birth to almost five years of age of a late-preterm patient diagnosed with LCC and carried out a thorough overview of pediatric patients described in the literature. It is important to gather serial clinical–radiological data from other patients to depict the natural history of this disease, aiming to deeply depict genotype-phenotype correlations and make the role of new therapeutics clearer.