• 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



BMD; CMD3B; DXS142; DXS164; DXS206; DXS230; DXS239; DXS268; DXS269; DXS270; DXS272; MRX85

Associated disorders

The DMD gene is associated with X-linked Duchenne Muscular Dystrophy (DMD) (MedGen UID: 3925), Becker Muscular Dystrophy (BMD) (MedGen UID: 182959) and dilated cardiomyopathy (DCM) (MedGen UID: 472068).

DMD is the only known cause of Duchenne and Becker muscular dystrophies. Test sensitivity is high when quantitative analysis and gene sequencing are combined. Deletion/duplication testing will detect approximately 55%-75% of the pathogenic DMD variants in Duchenne patients and slightly more (75%-90%) in Becker patients. Sequence analysis of DMD will detect an additional 20%-35% of Duchenne cases and 10%-20% of Becker cases. Relative contribution to dilated cardiomyopathy by DMD is unknown but is likely implicated in less than 1% of all cases of DCM.

DMD encodes dystrophin, a large cytoplasmic protein that bridges the intracellular cytoskeleton and the extracellular matrix by binding to actin at its C-terminus and dystroglycan at its N-terminus.

OMIM: 300377

Clinical condition
The DMD gene is associated with x-linked Duchenne muscular dystrophy (DMD; MedGen UID: 3925), Becker muscular dystrophy (BMD; MedGen UID: 182959), and dilated cardiomyopathy (DCM; MedGen UID: 472068). Collectively, conditions arising from pathogenic changes in DMD are referred to as dystrophinopathies.

DMD is characterized by childhood onset, progressive proximal muscle wasting and weakness, delayed milestones, pseudohypertrophy of the calves, and elevated serum creatine kinase levels (PMID: 14636778). The developmental milestones that are most typically delayed include the ability to sit and stand independently as well as climb and navigate stairs (PMID: 19945913). Muscle weakness results in a waddling gait and frequent falls. Gowers’ sign is typically present on exam by 5 years of age (PMID: 19945913). Smooth muscle of the gastrointestinal tract can be affected, leading to acute gastric dilatation or intestinal pseudoobstruction (PMID: 3380114). Progressive muscle degeneration typically leads to loss of independent ambulation by the early teens (PMID: 19945913). Scoliosis, kyphosis, and respiratory impairment accompany the early and late non-ambulatory periods (PMID: 19945913). The incidence of cardiomyopathy increases with age, and virtually all individuals with DMD exhibit cardiomyopathy after 18 years of age (PMID: 2312196). Non-progressive cognitive deficits in working memory and executive function are associated with DMD, and the rate of autistic spectrum disorders is greater than expected based on chance alone among individuals with DMD (PMID: 16417872, 18354150). Respiratory complications and progressive cardiomyopathy typically result in death prior to the third decade of life for individuals with DMD (PMID: 23097603).

BMD is a later-onset and clinically less severe muscular dystrophy, characterized by skeletal muscle weakness (PMID: 10529540). Onset generally does not occur until late childhood or adolescence, and the course is generally slower and less predictable than that of DMD (PMID: 10529540). Some individuals with BMD become non-ambulatory in their 30s, while others remain ambulatory with the use of minor aids, such as canes. Cardiomyopathy is common in patients with BMD, and heart failure is the most common cause of death after mid to late adulthood (PMID: 18513510, 9243091). Cognitive deficits are not as common or severe as those observed in DMD (PMID: 16417872).

DCM is often part of syndromic DMD and BMD but may also occur as an isolated condition (PMID: 9170393). DCM is defined by dilation and impaired contraction of the left or both ventricles and often presents as a conduction abnormality with rapid progression to congestive heart failure in individuals with a pathogenic DMD variant (PMID: 10099905, 9170393). Symptoms may include edema, shortness of breath, fatigue, palpitations, dizziness, syncope, and sudden cardiac arrest or death (PMID: 17325244, 25584016). Males with DCM typically present at 20 to 40 years old with a rapidly progressive course (PMID: 27230049). Females with a pathogenic variant in DMD are at an increased risk for isolated DCM and generally have symptom onset later in life (fourth or fifth decade) with a slower progression (PMID: 9170393).

Gene information
DMD encodes dystrophin, a large cytoplasmic protein that bridges the intracellular cytoskeleton and the extracellular matrix by binding to actin at its C-terminus and dystroglycan at its N-terminus (PMID: 11917091). Dystrophin is expressed primarily in smooth, skeletal, and cardiac muscle, as well as in the brain (PMID: 3380114).

Traditionally, the reading frame rule (Monaco rule) has been used in an attempt to predict the phenotypic outcome in patients with different pathogenic variants in DMD (PMID: 3384440). It is estimated that this rule can distinguish between the DMD and BMD phenotypes based on the type of deletion or duplication identified in the DMD gene with approximately 91-92% accuracy when there is a single affected individual in the family (PMID: 16770791). Exceptions to the rule exist, and it is important to carefully correlate clinical features with molecular test results in order to determine the ultimate care for the patient (PMID: 29305136).

There are a variety of databases that exist to aid with genotype and phenotype correlation, including the Leiden muscular dystrophy pages, the DMD mutation database, the eDystrophin database, and the UMD TREAT-NMD DMD mutations database. Most recently, Zhou et al. created the DMD toolkit, which is estimated to increase the accuracy of genotype and phenotype correlations by 3% more than previous methods, such as the reading frame rule (PMID: 28152980).

DMD exhibits x-linked inheritance, and affected individuals are male, although carrier females may manifest features of DMD-related conditions, specifically muscle weakness and cardiomyopathy (PMID: 22894145). In an affected individual, a pathogenic variant is expected to be inherited from the mother, or to occur de novo. When there is no previous family history of DMD, the mother of an affected son is estimated to be a carrier of a pathogenic variant two-thirds of the time (PMID: 8826437). Maternal genetic testing can help to determine if a variant is inherited or occurred de novo and to inform recurrence risk for multiple family members.

If the mother of a proband carries a pathogenic variant in DMD, that variant will be transmitted 50% of the time in each pregnancy. Males who inherit the variant will be affected and females who inherit the variant will be carriers. Germline mosaicism has been reported, and the empirical risk of germline mosaicism is estimated to be 15-20% (PMID: 2889144, 15527326, 2277383).

Female children of an affected male would inherit the pathogenic variant as carriers, while male children would not inherit this variant from an affected father.

Penetrance in carrier females varies and may be affected by x-chromosome inactivation (PMID: 9856563, 20630757, 7723955).

Due to the complex, multi-systemic nature of dystrophinopathies, affected individuals are best served by a multidisciplinary team that includes specialists in clinical genetics, neuromuscular conditions, cardiology, orthopedics, pulmonology, physical or occupational therapy, and nutrition (PMID: 19945913, 19945914). Detailed practice guidelines have been published for the diagnosis and management of patients with DMD-associated DCM by the American Academy of Pediatrics (PMID: 16322188), the American Academy of Neurology (PMC4773944), the American Thoracic Society (PMID: 15302625), the US Centers for Disease Control and Prevention (PMID: 19945913), and the DMD Care Considerations Working Group (PMID: 19945914), among others. Below is a summary of the recommendations:

Initial evaluations to consider upon identification of a pathogenic DMD variant:

  • Referral to a Muscular Dystrophy Association Care Center for coordination of care (PMID: 19945913)
  • Neuromuscular evaluation to determine the extent of muscular dystrophy and initiate corticosteroid or other pharmacotherapy when appropriate (PMID: 19945913)
  • Clinical genetics consultation and genetic counseling (PMID: 19945913):
    • Determine if therapeutics or clinical trials exist for the patient’s variant
    • Refer relevant family members for genetic testing and genetic counseling
  • Cardiac evaluation by electrocardiogram (ECG/EKG) and cardiac echocardiogram or MRI (PMID: 16322188)
  • Physical therapy assessment (PMID: 19945913)
  • Orthopedic evaluation for kyphosis or lordosis, contractures, and bone health management to minimize fractures (PMID: 19945913)
  • Evaluation and treatment by a pulmonologist; monitoring for sleep apnea (PMID: 19945913)
  • Developmental and neurocognitive evaluation (PMID: 19945913)
  • Individualized educational plan (PMID: 19945913)
  • Speech and language evaluation (PMID: 19945913)
  • Refer for dietary or nutritional consultation (PMID: 19945913)
  • Ensure that surgeons and other healthcare providers involved in the patient’s care are aware of the guidelines for people with a pathogenic variant in DMD receiving anesthesia or sedation (PMID: 19420153, 18079231)

Ongoing management:

  • Cardiac monitoring and pharmacotherapy as dictated by presentation (PMID: 16322188):
    • Assessment of cardiac function should occur at least once every 2 years until 10 years of age when evaluations should start annually.
    • Abnormalities of ventricular function on noninvasive cardiac imaging studies warrant increased surveillance and should prompt initiation of pharmacological therapy, irrespective of the age at which they are detected.
    • Signs or symptoms of abnormalities of cardiac rhythm should be promptly investigated with Holter or event monitor recording and should be treated.
  • Monitor use of corticosteroid therapy and other pharmacotherapy when appropriate, as determined by the neuromuscular specialist and other members of multidisciplinary team and family (PMID: 19945913)
  • Continued care by a pulmonologist (PMID: 15302625):
    • At least one visit at 4-6 years of age prior to confinement to a wheelchair to obtain baseline pulmonary function testing, for anticipatory medical guidance regarding the potential respiratory complications of the disease, and to assess the need for intensified therapy
    • Twice per year after confinement to a wheelchair, fall in vital capacity below 80% predicted, or 12 years of age
  • Orthopedic care of scoliosis/kyphosis/lordosis/contractures and bone health management to minimize fractures as indicated (PMID: 19945913)
  • Annual evaluation for sleep-disordered breathing with polysomnography and continuous carbon dioxide monitoring (PMID: 15302625)
  • Dietary or nutritional consultation at initiation of glucocorticoids and if the patient is underweight or overweight, if surgery is planned, if dysphagia is present, or patient is chronically constipated (PMID: 15302625)
  • rovide routine preventive care, including routine immunizations, annual influenza immunization, avoidance of second-hand smoke, and avoidance of obesity

The exon skipping agent eteplirsen (Exondys 51) was approved by the FDA in 2016 to treat patients with DMD caused by a variant amenable to exon 51 skipping (PMID: 29278896, 29254734). Other therapeutic approaches, such as stop codon readthrough agents and utrophin modulators, aim to replace dystrophin in myocytes, while other treatments aim to prevent or repair muscle damage caused by the absence of dystrophin (PMID: 28152217). Multiple trials are underway for the treatment of DMD. This is an active area of ongoing research, and it is important to stay updated with new therapeutic options and changes to practice guidelines as they become available, or refer to a specialty center for up-to-date management.

Additional references

Leiden Muscular Dystrophy pages. Center for Human and Clinical Genetics, Leiden University Medical Center. http://www.dmd.nl. Accessed January 15, 2018.

The DMD mutation database. UMD-DMD France. http://www.umd.be/DMD/W_DMD/index.html. Accessed January 15, 2018.

eDystrophin: a database dedicated to human dystrophin variants produced by in-frame DMD gene mutations. http://edystrophin.genouest.org. Accessed January 15, 2018.

The UMD TREAT-NMD DMD mutations database. http://umd.be/TREAT_DMD. Accessed January 15, 2018.

The DMD toolkit. http://www.dmd-registry.com (in Chinese) and http://github.com/zhoujp111/DMDtoolkit. Accessed January 15, 2018.

Review date: January 2018

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
DMD* NM_004006.2

*DMD: Analysis guarantees del/dup detection at single-exon resolution.