Marinesco-Sjögren Syndrome (MSS, OMIM 248800) is a rare, autosomal recessive disorder featuring cataracts, cerebellar ataxia, mental retardation, muscle weakness, short stature, and frequently hypergonadotropic hypogonadism.
MSS is usually evident at birth because of hypotonia. The cataracts are often not present at birth but may appear rapidly during childhood. Motor milestones are significantly delayed with ataxia becoming noticeable by the time the child can sit. Most patients are eventually able to ambulate with a walker. Linear growth is poor and pubertal development may not occur because of hypergonadotropic hypogonadism. Mental retardation is generally mild to moderate in severity if it is present at all. Dysarthria is common. Neurologic deterioration is slow to absent and prolonged survival is possible, but the muscle weakness may be progressive in adulthood. Less commonly reported features include optic atrophy, brachydactyly, and cone epiphyses.
MSS is inherited as an autosomal recessive trait
with complete penetrance in both sexes. It is
panethnic, but very rare except in genetic
isolates, such as one in rural
The diagnosis should be suspected based on the clinical symptomatology. An ophthalmologic exam (cataracts) and magnetic resonance imaging of the brain (cerebellar atrophy particularly involving the vermis) can be helpful. Muscle biopsy findings are generally non-specific, although ragged red fibers and abnormal mitochondria have been reported. Multilamellar inclusions can be present in muscle and conjunctival biopsies as well as in cultured fibroblasts. Metabolic testing is normal.
Treatment is supportive and based on symptomatology. Removal of the cataracts and placement of an artificial lens implant is often required to preserve vision. Physical and occupational therapy, special education, and computers are essential given their visual and motor problems as well as dysarthria. Hormonal replacement therapy is needed if hypogonadism is present.
The differential diagnosis includes: MSS with chylomicronemia (607692), congenital cataracts, facial dysmorphism, and neuropathy (604168), mitochondrial disorders, and the carbohydrate deficient glycoprotein syndromes.
William R. Wilcox, M.D., Ph.D.