SMA is characterized by anterior horn cell degeneration, which causes a symmetrical muscle weakness and wasting.
Other symptoms can include joint contractures, respiratory insufficiency, and feeding and sleep difficulties. Sub-types have been created, although the phenotype can span a broad continuum and sub-types are not clearly delineated.
Subtypes of SMA include:
- Type 0: prenatal onset of severe joint contractures and weakness at birth; lifespan ranges from days to 2-6 months
- Type I (Werdnig-Hoffman disease): most severe form of SMA with an onset of severe weakness before 6 months of age; affected individuals usually die by 2 years of age
- Type II (Dubowitz disease): intermediate in severity between Types I and III, with an onset of symptoms after 6 months of age; death occurs in childhood or young adulthood
- Type III (Kugelberg-Welander disease): mildest form of childhood-onset SMA, with symptoms usually beginning after 10 months; affected individuals can survive into adulthood
- Type IV: onset of muscle weakness in second or third decade with normal lifespan
All SMA sub-types are caused by mutations in the survival motor neuron (SMN1) gene (5q11.2-q13.3). SMN1 is deleted in about 95-98% of individuals with SMA. Point mutations are also known in this gene. Approximately 2-5% of affected individuals have one deletion and one point mutation. Approximately 2% of affected individuals have a de novo mutation meaning only one parent is an SMA carrier.
This carrier assay tests for the common SMN1 deletion only; point mutations will not be detected. Approximately 5-8% of carrier individuals will have a normal SMN1 copy number of two, but both copies will be on the same chromosome (in cis) with a deletion on the second chromosome. This assay will not detect these carrier individuals. This assay will not report SMN2 copy number.
Deletions of the SMN1 gene are found in approximately 95% of SMA patients, but the frequency is less in the milder (type II and III) variants. Affected individuals with 0 copies of SMN1 seem to have milder form of the disease with increased copy numbers of the SMN2 gene. Deletions of the SMN1 gene are the most common pathologic mechanism for SMA, however, other gene rearrangements have been described in affected individuals, including hybrid or fusion SMN genes and deleterious point mutations in the SMN1 gene. Thus, the lack of a deletion does not necessarily rule out this diagnosis, and further testing may be required.
Turn around time: Results can be expected 2 weeks from the time that the sample is received at the laboratory.
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Genetic carrier screening is performed through our sister laboratory, Eurofins EGL Genetics.
Eurofins EGL Genetics has been providing superior, cutting-edge service for more than 47 years. Their expertise spans common and rare genetic disease testing, genomic variant interpretation, test development, and research. Eurofins EGL Genetics is a CLIA-certified and CAP-accredited laboratory. They work with clients across the United States and from more than 45 countries to help improve patient diagnosis.
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