Marinesco-Sjögren syndrome due to SIL1 mutations with a comment on the clinical phenotype

Background: Marinesco-Sjögren syndrome is an autosomal recessive cerebellar ataxia, characterised by cerebellar ataxia, myopathy, cataracts and intellectual disability, due to mutations in the SIL1 gene. Methods: The clinical features and two novel SIL1 mutations of four Dutch patients with Marinesco-Sjögren syndrome are described and compared to the literature on genetically proven Marinesco-Sjögren patients. Results: The core phenotype of this syndrome appears homogeneous, but: [1] cataract can develop later than the motor and cognitive signs; [2] myopathy is an early feature that seems progressive during the course of the disease; [3] serum creatine kinase is normal or only mildly elevated; [4] peripheral neuropathy is absent; and [5] a variable degree of intellectual disability is present in most Marinesco-Sjögren patients. Conclusions: Because the late appearance of some hallmarks and the uncertainty as to whether incomplete phenotypes occur, SIL1 mutation analysis is helpful early in the diagnostic work-up of children with suspected inherited ataxias.