Marinesco-Sjögren Syndrome

Excerpt

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: The diagnosis of MSS is established in an individual with typical clinical findings and/or biallelic pathogenic variants in SIL1 identified by 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; developmental support and education programs tailored to the individual's developmental needs; cataract extraction as needed; treatment of strabismus per ophthalmologist; hormone replacement therapy for primary gonadal failure at the expected time of puberty; feeding support as needed for poor weight gain; management of scoliosis and other skeletal manifestations per orthopedist.

Surveillance: Assessment by child or adult neurologist and physiatrist and/or physical therapist annually or as needed; monitor developmental progress and educational needs at each visit; annual ophthalmologic examination beginning in infancy; monitor pubertal development throughout adolescence per endocrinologist; assess growth and feeding at each visit; clinical assessment for scoliosis at each visit, with radiographs as needed.

Genetic counseling: MSS is inherited in an autosomal recessive manner. The parents of an affected child are presumed to be heterozygous for an MSS-related pathogenic variant. If both parents are known to be heterozygous for a SIL1 pathogenic variant, each sib of an affected individual has at conception 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. If biallelic SIL1 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.