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Marinesco-Sjögren syndrome (MSS) belongs to the group of autosomal recessive cerebellar ataxias. Prevalence is most likely below 1 to 9/1 000 000. Disease onset occurs in infancy. Cardinal features of MSS are cerebellar ataxia, congenital cataract, and delayed psychomotor development. Dysarthria, nystagmus, muscle weakness and hypotonia are frequent symptoms. Areflexia is associated with a demyelinating peripheral neuropathy. Some patients show episodes of rhabdomyolysis with sustained or episodic elevation of serum creatin kinase. Hypergonadotropic hypogonadism is a frequently associated feature. Muscle pathology consists of extensive neurogenic atrophy and myopathic changes with rimmed vacuoles. Cerebellar cortical atrophy with vacuolated or binuclear Purkinje cells is also observed. It has been suggested that the MSS with myoglobinuria and congenital cataracts-facial dysmorphism-neuropathy (CCFDN) syndromes are genetically identical as they both map to chromosome 18qter. In contrast, a locus for classical MSS has been assigned to chromosome 5q31 and mutations have recently been identified in SIL1, a gene encoding a factor involved in proper protein folding. Loss of SIL1 function results in accumulation of unfolded proteins, harmful to the cell. Diagnosis is based on clinical symptoms. Ophthalmologic examination should be performed to detect cataracts and MRI (Magnetic Resonance Imaging) scan allows investigation of cerebellar atrophy particularly involving the vermis. Muscle biopsy findings are generally non-specific. Prenatal diagnosis with molecular genetic techniques can be performed if a mutation is known in the family. Treatment is symptomatic. Cataracts often require surgical removal to preserve vision. Hormonal replacement therapy may be needed if hypogonadism is present. Physical and occupational therapy are crucial. Patients can survive to old age, with varying disability. |