Clinical characteristics: Marinesco-Sjögren syndrome (MSS) is characterized by cerebellar ataxia with cerebellar atrophy, dysarthria, nystagmus, early-onset (not necessarily congenital) cataracts, myopathy, muscle weakness, and hypotonia. Additional features may include psychomotor delay, hypergonadotropic hypogonadism, short stature, and various skeletal abnormalities. Children with MSS usually present with muscular hypotonia in early infancy; distal and proximal muscular weakness is noticed during the first decade of life. Later, cerebellar findings of truncal ataxia, dysdiadochokinesia, nystagmus, and dysarthria become apparent. Motor function worsens progressively for some years, then stabilizes at an unpredictable age and degree of severity. Cataracts can develop rapidly and typically require lens extraction in the first decade of life. Although many adults have severe disabilities, life span in MSS appears to be near normal.
Diagnosis/testing: Diagnosis is established in an individual with typical clinical findings and/or biallelic pathogenic variants of SIL1 identified on molecular genetic testing. Electron-microscopic ultrastructural changes on muscle biopsy are thought to be specific to MSS.
Management: Treatment of manifestations: Symptomatic treatment of muscular manifestations usually by pediatric or adult neurologists and physiatrists and/or physical therapists; education programs tailored to the individual's developmental needs; cataract extraction as needed; hormone replacement therapy for primary gonadal failure at the expected time of puberty.
Surveillance: Regular follow up with a child or adult neurologist and physiatrist and/or physical therapist; ophthalmologic examination at regular intervals beginning in infancy.
Genetic counseling: Marinesco-Sjögren syndrome (MSS) is inherited in an autosomal recessive manner. The parents of an affected child are obligate heterozygotes and therefore carry one pathogenic variant. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal and preimplantation genetic testing are possible if the pathogenic variants in the family are known.
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