Invitae Dystrophinopathies Test


Test description

This test is for the dystrophinopathies, a spectrum of muscle diseases that are caused by pathogenic variants in the DMD gene. The DMD gene is associated with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and dilated cardiomyopathy (CMD3B).

The dystrophinopathies are similar to other muscular dystrophies in terms of age of onset and clinical presentation. Diagnostic genetic testing may obviate the need for a muscle biopsy. Identification of the underlying genetic cause may direct medical treatment, predict outcome for the patient, or clarify recurrence risk. Identification of the specific DMD pathogenic variant may also be a requirement for enrollment in clinical trials.

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Primary panel (1 gene)


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

Alternative tests to consider

DMD can also be ordered as part of broader panels to test for cardiomyopathy disorders. Depending on the individual’s clinical and family history, one of these broader panels may be appropriate. Any of these broader panels can be ordered at no additional charge.

  • Duchenne muscular dystrophy (DMD)
  • Becker muscular dystrophy (BMD)
  • Dilated cardiomyopathy (DCM)

Duchenne muscular dystrophy (DMD) is characterized by childhood onset, progressive proximal muscle wasting and weakness, delayed milestones, pseudohypertrophy of the calves, and elevated serum creatine kinase levels. Usually, only males are affected, although in some cases females may be affected. Becker muscular dystrophy (BMD) is a less clinically severe muscular dystrophy, characterized by later-onset skeletal muscle weakness. Despite a milder skeletal muscle involvement in BMD patients, heart failure from dilated cardiomyopathy is a common cause of morbidity. Some genotype-phenotype correlation is possible, as the majority of pathogenic variants causing DMD are truncating, whereas pathogenic variants causing BMD are usually in-frame, leading to residual DMD function. Both DMD and BMD patients are affected by cardiomyopathy. DMD-related dilated cardiomyopathy can occur in female carriers of DMD and in some cases can be the presenting finding in male individuals who have BMD and little or no evidence of skeletal muscle disease.

The gene DMD is the only known cause of Duchenne and Becker muscular dystrophies. Test sensitivity is high when quantitative analysis and gene sequencing are combined. This test includes both full-gene sequencing and deletion/duplication analysis of the DMD gene.

For DMD patients:

  • Deletion/duplication testing will detect approximately 55% to 75% of cases.
  • Sequence analysis will detect an additional 20% to 35% of cases.

For BMD patients:

  • Deletion/duplication testing will detect approximately 75% to 90% of cases.
  • Sequence analysis will detect an additional 10% to 20% of cases.

Relative contribution to dilated cardiomyopathy by DMD is unknown, but it is likely less than 1% of all cases of DCM.

The dystrophinopathies are inherited as X-linked recessive disorders. Female carriers are typically unaffected, although skewed X inactivation can result in symptoms.

Dystrophinopathies are fully penetrant disorders in males. Onset of symptoms in DMD typically occurs before age 5 and individuals usually lose their ability to walk independently during early adolescence. Individuals with BMD typically have a later onset of disease and greater variability in terms of the age at which assistance with walking will be required. Female carriers may also be affected,though symptoms are generally less severe than in affected males. Female carriers can present with symptoms from early childhood through adulthood and may depend in part on patterns of X-chromosome inactivation.

Approximately 1 in 3,000 to 1 in 5,000 newborn males will be affected with DMD. BMD is much less common (approximately 1 in 20,000 male births). DMD-related dilated cardiomyopathy in the absence of skeletal muscle disease is very rare; dilated cardiomyopathy, however, is a near-universal finding in males with DMD.

A diagnosis of DMD typically occurs around 5 years of age, but DMD may be suspected much earlier due to delays in the achievement of developmental milestones. Initial symptoms can include delayed walking, frequent falls, difficulty running, and difficulty climbing stairs. The presence of the Gower’s sign in a male child should trigger the diagnostic investigation of DMD. In the following scenarios, DMD should be considered, irrespective of family history:

  • observation of abnormal muscle function in a male child
  • detection of an increase in serum CK tested for unrelated indications
  • the discovery of increased transaminases

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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
DMD* NM_004006.2

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