Ordering
  • Test code: 03303
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
Billing
 
Print this page
  1. Test Catalog
  2. Invitae Emery-Dreifuss Muscular Dystrophy Panel

Invitae Emery-Dreifuss Muscular Dystrophy Panel

Test description

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.

Genes tested

Primary panel

EMD FHL1 LMNA

Add-on Preliminary-evidence Genes for Emery-Dreifuss Muscular Dystrophy

SUN1 SUN2 SYNE1 SYNE2 TMEM43

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

Order test

Primary panel (3 genes)

EMD FHL1 LMNA

Panel details and technical assay limitations
Add-on Preliminary-evidence Genes for Emery-Dreifuss Muscular Dystrophy (5 genes)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

SUN1 SUN2 SYNE1 SYNE2 TMEM43

Panel details and technical assay limitations

Alternative tests to consider

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):

Clinical information

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.

GeneInheritanceProportion of EDMD casesEDMD subtype(s)
Autosomal dominantAutosomal recessiveX-linked
EMD ✓ 60% of X-linked cases EDMD1
FHL1 ✓ 10% of X-linked cases EDMD6
LMNA ✓ ✓ 45% of autosomal dominant cases EDMD2, EDMD3
SUN1* ✓ Unknown Unknown
SUN2* ✓ Unknown Unknown
SYNE1* ✓ Unknown EDMD4
SYNE2* ✓ Unknown EDMD5
TMEM43* ✓ Unknown EDMD7

*Preliminary-evidence gene

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.

  1. Emery, AE. Emery-Dreifuss syndrome. J. Med. Genet. 1989; 26(10):637-41. PMID: 2685312
  2. Zhang, Q, et al. Nesprin-1 and -2 are involved in the pathogenesis of Emery Dreifuss muscular dystrophy and are critical for nuclear envelope integrity. Hum. Mol. Genet. 2007; 16(23):2816-33. PMID: 17761684
  3. Norwood, FL, et al. Prevalence of genetic muscle disease in Northern England: in-depth analysis of a muscle clinic population. Brain. 2009; 132(Pt 11):3175-86. PMID: 19767415
  4. Bonne, G, et al. Emery-Dreifuss Muscular Dystrophy. 2004 Sep 29. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1436/ PMID: 20301609
  5. Liang, WC, et al. TMEM43 mutations in Emery-Dreifuss muscular dystrophy-related myopathy. Ann. Neurol. 2011; 69(6):1005-13. PMID: 21391237
  6. Bonne, G, Quijano-Roy, S. Emery-Dreifuss muscular dystrophy, laminopathies, and other nuclear envelopathies. Handb Clin Neurol. 2013; 113:1367-76. PMID: 23622360
  7. Fanin, M, et al. Dominant muscular dystrophy with a novel SYNE1 gene mutation. Muscle Nerve. 2015; 51(1):145-7. PMID: 25091525

Assay and technical information

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, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

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
EMD NM_000117.2
FHL1 NM_001449.4
LMNA NM_170707.3
SUN1 NM_001130965.2
SUN2 NM_015374.2
SYNE1 NM_033071.3
SYNE2 NM_182914.2
TMEM43 NM_024334.2

Clinical resources
Invitae brochure Neurology gene list
Patient resources
Patient guide: Genetic testing simplified
Test information
Forms page Specimen requirements page

References

  1. Bonne, G, Quijano-Roy, S. Emery-Dreifuss muscular dystrophy, laminopathies, and other nuclear envelopathies. Handb Clin Neurol. 2013; 113:1367-76. PMID: 23622360
  2. Bonne, G, et al. Emery-Dreifuss Muscular Dystrophy. 2004 Sep 29. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1436/ PMID: 20301609
  3. Emery, AE. Emery-Dreifuss syndrome. J. Med. Genet. 1989; 26(10):637-41. PMID: 2685312
  4. Fanin, M, et al. Dominant muscular dystrophy with a novel SYNE1 gene mutation. Muscle Nerve. 2015; 51(1):145-7. PMID: 25091525
  5. Liang, WC, et al. TMEM43 mutations in Emery-Dreifuss muscular dystrophy-related myopathy. Ann. Neurol. 2011; 69(6):1005-13. PMID: 21391237
  6. Norwood, FL, et al. Prevalence of genetic muscle disease in Northern England: in-depth analysis of a muscle clinic population. Brain. 2009; 132(Pt 11):3175-86. PMID: 19767415
  7. Zhang, Q, et al. Nesprin-1 and -2 are involved in the pathogenesis of Emery Dreifuss muscular dystrophy and are critical for nuclear envelope integrity. Hum. Mol. Genet. 2007; 16(23):2816-33. PMID: 17761684

Headquarters | 458 Brannan Street, San Francisco, CA 94107

Laboratory & Shipping | 475 Brannan Street, Suite 230, San Francisco, CA 94107 | www.invitae.com

In the US | clientservices@invitae.com | p: 800-436-3037 | f: 415-276-4164

Outside the US | globalsupport@invitae.com or visit www.invitae.com/contact

©2015 Invitae Corp. All rights reserved.