The Invitae Emery-Dreifuss Muscular Dystrophy Panel analyzes up to eight genes that are associated with Emery-Dreifuss muscular dystrophy (EDMD), a disorder characterized by a clinical triad of joint contractures, progressive muscle weakness, and cardiac disease. These genes were curated based on current available evidence to provide a comprehensive test for the genetic causes of EDMD.
Identification of the underlying genetic cause can be useful in confirming a diagnosis of EDMD, ruling out other disorders with similar clinical features, and informing recurrence risk.
EMD FHL1 LMNA
SUN1 SUN2 SYNE1 SYNE2 TMEM43
EMD FHL1 LMNA
SUN1 SUN2 SYNE1 SYNE2 TMEM43
For a broader analysis of genes associated with muscular dystrophies, clinicians may consider the Invitae Comprehensive Muscular Dystrophy Panel.
For a broader analysis of the genetics of hereditary neuromuscular disorders (muscular dystrophies, myopathies, and congenital myasthenic syndrome):
Emery-Dreifuss muscular dystrophy (EDMD) is characterized by a clinical triad of joint contractures, progressive muscular weakness, and cardiac disease. Age of onset, symptom severity, and progression of muscle and cardiac involvement are variable. At onset, muscle weakness typically has a humero-peroneal distribution; in later stages of the disease, muscle weakness also affects the scapular and pelvic girdle muscles. Conduction defects are the most frequent cardiac abnormalities and atrial paralysis is almost pathognomonic for EDMD. Other cardiac findings include arrhythmias and dilated cardiomyopathy. Cardiac involvement may precede significant muscle weakness and can lead to death resulting from sudden cardiac failure.
|Gene||Inheritance||Proportion of EDMD cases||EDMD subtype(s)|
|Autosomal dominant||Autosomal recessive||X-linked|
|EMD||✓||60% of X-linked cases||EDMD1|
|FHL1||✓||10% of X-linked cases||EDMD6|
|LMNA||✓||✓||45% of autosomal dominant cases||EDMD2, EDMD3|
Pathogenic variants in the EMD and FHL1 genes account for 60% and 10% of individuals with X-linked EDMD, respectively. The LMNA gene accounts for 45% of autosomal dominant EDMD. The percentage of individuals with EDMD caused by the SUN1, SUN2, SYNE1, SYNE2 and TMEM43 genes is unknown.
EDMD can be inherited in an autosomal dominant, autosomal recessive, or an X-linked pattern.
The penetrance of EMD-, FHL1-, and LMNA-associated EDMD is high. Most cases of EMD-associated EDMD have onset in the first two decades of life; however, later onset cases have been reported, which may be mistaken for reduced penetrance.
The overall prevalence of EDMD is unknown. The prevalence of X-linked EDMD is estimated at 1 in 100,000. Autosomal dominant forms of LMNA-associated EDMD are thought to be more common than X-linked EDMD associated with EMD.
The clinical spectrum of EDMD is variable. Genetic testing may confirm a suspected diagnosis or rule out disorders with similar symptoms. A genetic diagnosis may also help predict disease progression and inform recurrence risk.
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|