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

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.

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.

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.

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.