• 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




Associated disorders

The DES gene is associated with autosomal dominant and recessive myofibrillar myopathy 1 (MFM1) (MedGen UID: 330449). It is also associated with autosomal recessive limb-girdle muscular dystrophy type 2R (LGMD2R)(MedGen UID: 815467) and autosomal dominant dilated cardiomyopathy (DCM) (MedGen UID: 387998).

DES mutations account for approximately 7% of known familial cases of myofibrillar myopathy, and the genetic cause is understood for only approximately half of all such cases. DES mutations are a rare cause of limb girdle muscular dystrophy and DCM.

DES encodes desmin, a cardiac and skeletal muscle protein that forms an intermediate filament connecting the contractile apparatus (by encircling the Z-band) to the sarcolemma and cytoplasmic organelles. Desmin functions to transmit force.

  1. Pugh TJ, et al. The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. 2014 Genet Med Aug; 16(8):601-608. PMID: 24503780
  2. Hedberg, C, et al. Autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy 7 is caused by a DES mutation. Eur. J. Hum. Genet. 2012; 20(9):984-5. doi: 10.1038/ejhg.2012.39. PMID: 22395865
  3. Muntoni, F, et al. Disease severity in dominant Emery Dreifuss is increased by mutations in both emerin and desmin proteins. Brain. 2006; 129(Pt 5):1260-8. doi: 10.1093/brain/awl062. PMID: 16585054
  4. Hong, D, et al. A series of Chinese patients with desminopathy associated with six novel and one reported mutations in the desmin gene. Neuropathol. Appl. Neurobiol. 2011; 37(3):257-70. doi: 10.1111/j.1365-2990.2010.01112.x. PMID: 20696008
  5. Dalakas, MC, et al. Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene. N. Engl. J. Med. 2000; 342(11):770-80. doi: 10.1056/NEJM200003163421104. PMID: 10717012
  6. McLaughlin, HM, et al. Compound heterozygosity of predicted loss-of-function DES variants in a family with recessive desminopathy. BMC Med. Genet. 2013; 14:68. doi: 10.1186/1471-2350-14-68. PMID: 23815709
  7. Selcen, D, Engel, AG. Myofibrillar Myopathy. 2005 Jan 28. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1499/ PMID: 20301672
  8. Nigro, V, Savarese, M. Genetic basis of limb-girdle muscular dystrophies: the 2014 update. Acta Myol. 2014; 33(1):1-12. PMID: 24843229
  9. Selcen, D, et al. Myofibrillar myopathy: clinical, morphological and genetic studies in 63 patients. Brain. 2004; 127(Pt 2):439-51. doi: 10.1093/brain/awh052. PMID: 14711882
  10. Selcen, D. Myofibrillar myopathies. Curr. Opin. Neurol. 2010; 23(5):477-81. doi: 10.1097/WCO.0b013e32833d38b0. PMID: 20664348
  11. Selcen, D. Myofibrillar myopathies. Neuromuscul. Disord. 2011; 21(3):161-71. doi: 10.1016/j.nmd.2010.12.007. PMID: 21256014


OMIM: 125660

Clinical condition

The phenotypes caused by pathogenic variants in DES are a clinically heterogeneous spectrum of conditions, sometimes called desminopathies. They are generally characterized by skeletal and cardiac muscle myopathy, including myofibrillar myopathy (MFM1; MedGen UID: 330449), limb-girdle muscular dystrophy (LGMD; MedGen UID: 151940), and dilated cardiomyopathy (DCM; MedGen UID: 387998; PMID: 20718792).

MFM1 is typically characterized by slowly progressive distal muscle weakness, cardiomyopathy, and cardiac conduction disease, although the disease is highly variable within and among families with regard to onset (childhood to adulthood), features, and severity (PMID: 20718792, 14991347). Skeletal myopathy usually begins in the lower extremities, followed by the upper extremities, and slowly spreads proximally to other muscle groups (PMID: 20718792). A muscle biopsy can show desmin-positive aggregates and degenerative changes of the myofibrillar apparatus; however, these are not specific to DES-related myopathy (PMID: 19561540, 9697706). Cardiomyopathy can be hypertrophic, dilated, or restrictive, and is often accompanied or preceded by conduction defects and arrhythmia (PMID: 20718792).

DES-related LGMD is characterized by progressive proximal weakness and non-specific atrophy, affecting both the shoulder and pelvic girdles with cardiac conduction block without cardiomyopathy. The age of onset is typically in the teens or twenties (PMID: 23687351, 24843229).

DCM is defined by dilation and impaired contraction of the left or both ventricles (PMID: 10099905). DES-related DCM can be associated with conduction defects, and symptoms may include edema, shortness of breath, fatigue, palpitations, dizziness, syncope, and sudden cardiac arrest or death (PMID: 17325244, 25584016).

Gene information

DES encodes the protein desmin, which is the main intermediate filament protein in skeletal, cardiac, and smooth muscle, and interacts with other proteins to form a continuous cytoskeletal network maintaining the spatial relationship between muscle contractile apparatus and other structural cellular elements (PMID: 7188712, 20718792). Within this cytoskeletal network, desmin provides maintenance of cellular integrity, force transmission, and mechanochemical signaling, enabling the heart to contract in a coordinated fashion (PMID: 20718792, 23143191).


Pathogenic variants in DES can cause disease in an autosomal dominant or recessive manner, and may be inherited or occur de novo (PMID: 9697706, 24843229, 20718792). In autosomal dominant disease, an affected individual with a pathogenic variant has a 50% chance of passing that variant onto their offspring. In autosomal recessive disease, affected individuals have two pathogenic variants, one in each copy of their DES genes. Affected individuals will pass one pathogenic DES variant to all of their children. DES pathogenic variants exhibit reduced penetrance and variable expression, meaning that it is possible that an individual with a disease-causing variant will not develop symptoms of the disease within their lifetime.


While no comprehensive surveillance and management guideline currently exists across all DES-related conditions, the recommendations below may be appropriate for conditions within the desminopathy spectrum.

Upon discovery of a DES pathogenic variant, referral to a multidisciplinary clinic with expert specialists is recommended, so that the patient can be screened for appropriate symptoms of DES-related conditions and managed accordingly (PMID: 25313375, 19254666).

Initial evaluations after a DES pathogenic variant is identified include:

  • cardiac screening in the form of medical history, physical exam, electrocardiogram (EKG/ECG), and echocardiogram (PMID: 19254666)
  • neuromuscular evaluation to establish the presence and extent of disease by clinical exam, serum creatine kinase level, nerve conduction velocity testing, needle electromyography, or muscle biopsy with electron microscopy (PMID: 25313375, 25037088)
  • pulmonary function testing, including spirometry and maximal inspiratory and expiratory force in upright and supine positions, for adult patients with signs of muscular dystrophy to identify and treat respiratory insufficiency (PMID: 25313375)
  • genetic counseling for individuals and families to interpret genetic test results and arrange familial testing (PMID: 26186385)
  • genetic testing for at-risk family members of an individual with a pathogenic DES variant (PMID: 19254666, 21787999)

Ongoing evaluations and management of symptoms include:

  • Cardiac screening for DES-related cardiac disease is recommended annually in children and every 1-3 years in adults (PMID: 19254666). It is recommended to treat cardiomyopathy with or without arrhythmia by a combination of medication, device therapy (e.g., implantable cardioverter defibrillator or pacemaker), surgical procedures (e.g., catheter ablation or cardiac resynchronization), and potentially heart transplantation (PMID: 23747642, 29097320).
  • Patients with muscular dystrophy may have dysphagia, frequent aspiration, or weight loss, further complicating their course of disease. These patients’ nutrition should be monitored, and they should be referred for swallowing or gastroenterology evaluations to assess and manage swallowing function, risk of aspiration, and for consideration of a gastrostomy or jejunostomy tube (PMID: 25313375).
  • Patients should be monitored for the development of spinal deformities (PMID: 25313375). Periodic assessments as well as ongoing therapies by physical and occupational therapists are recommended, along with appropriate stretches, exercises, braces, assistive devices, and potential surgery to preserve mobility and function (PMID: 25313375).
  • Discussions surrounding the disease progression, loss of mobility, need for assistance, medical complications, and end-of-life care should be had proactively with patients and family (PMID: 25313375).
  • Pulmonary function tests should be repeated at the onset of respiratory difficulty and managed with appropriate assisted ventilation (PMID: 25313375).

Review date: December 2017

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 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
DES NM_001927.3