Marinesco-Sjogren syndrome (MSS) is characterized by cerebellar ataxia with cerebellar atrophy, early-onset (not necessarily congenital) cataracts, mild to severe mental retardation, hypotonia, and muscle weakness. Additional features include short stature, various skeletal abnormalities including scoliosis, hypergonadotropic hypogonadism, dysarthria, strabismus, and nystagmus. 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, 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 are severely handicapped, life span in MSS seems to be near normal.
Diagnosis is based on clinical, radiographic, and neuroimaging studies. Serum CK concentrations are normal or moderately increased (usually 2-4 times the upper normal limits). Light microscopy shows variation in muscle fiber size, atrophic fibers, fatty replacement, and rimmed vacuole formation. Electron microscopy reveals autophagic vacuoles, membranous whorls, and electron-dense double-membrane structures associated with nuclei, which are thought to be a specific ultrastructural feature of MSS. SIL1 (5q31) is the only gene known to be associated with Marinesco-Sjogren syndrome and mutations in SIL1 are identified in 50-60% of individuals fulfilling diagnostic criteria.
MSS is inherited in an autosomal recessive manner. MSS has previously been called Garland-Moorhouse syndrome, Marinesco-Garland syndrome, and hereditary oligophrenic cerebello-lental degeneration. MSS is panethnic; the prevelance is not known, but the carrier frequency in Finland is estimated to be approximately 1 in 96.
For patients with suspected Marinesco-Sjogren syndrome, sequence analysis is recommended as the first step in mutation identification. For patients in whom mutations are not identified by full gene sequencing, deletion/duplication analysis is appropriate.
- GeneTests: Marinesco-Sjogren Syndrome. http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=mss.
- OMIM: Marinesco-Sjogren Syndrome. http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=248800.
This test is indicated for:
- Confirmation of a clinical diagnosis of Marinesco-Sjogren syndrome in individuals who have tested negative for sequence analysis
- Carrier testing in adults with a family history of Marinesco-Sjogren syndrome who have tested negative for sequence analysis
Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient's clinical and/or biochemical phenotype.
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.
Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of EGL Genetics, please submit a copy of the sequencing report with the test requisition.
- Sequence analysis of the SIL1 gene is available and is required before deletion/duplication analysis.
- Prenatal testing is available to couples who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.