• Test code: 03292
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit

Invitae Congenital Muscular Dystrophy Panel

Test description

The Invitae Congenital Muscular Dystrophy Panel analyzes 27 genes that are associated with congenital muscular dystrophies, a heterogeneous group of neuromuscular disorders with widely variable symptom severity. These genes were curated based on current available evidence to provide a comprehensive test for the genetic causes of congenital muscular dystrophies.

Given that congenital muscular dystrophies are a heterogeneous group of disorders, identification of the underlying genetic cause can help predict outcome for the individual and inform recurrence risk.

FKTN: Analysis includes the intronic variant NM_001079802.1:c.647+2084G>T (also known as NM_001079802.1:c.648-1243G>T) and the ~3 kb retrotransposon insertion in the 3’ UTR at position NM_001079802​.1:c.*4392_*4393.

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Primary panel (27 genes)


Alternative tests to consider

In some cases, muscular dystrophies may have overlapping features with myopathies. If a congenital myopathy is suspected, clinicians may consider the Invitae Congenital Myopathy Panel, or the Invitae Comprehensive Myopathy panel.

For a broader analysis of the genetics of hereditary neuromuscular disorders (muscular dystrophies, myopathies, and congenital myasthenic syndrome):

The congenital muscular dystrophies (CMDs) are a group of genetically and clinically heterogeneous conditions that are characterized by congenital hypotonia, delayed motor development, and the early onset of progressive muscle weakness and wasting associated with a dystrophic pattern on muscle biopsy. The degree of muscular or central nervous system involvement is variable within a spectrum and ranges from severe infantile onset hypotonia with feeding and respiratory complications and structural brain and eye abnormalities to moderate motor delay and mild or moderate limb-girdle involvement during childhood. Since delay of motor skill acquisition may be a presenting symptom of CMD, onset of manifestations before age two years may be a reasonable diagnostic criterion, although the exact age at onset may be difficult to define in some cases, especially for the milder variants.

CMD typeGeneSubtype(s)InheritanceAssociated phenotype
Autosomal dominantAutosomal recessiveX-linked
Type VI collagenopathies COL6A1, COL6A2, COL6A3, COL12A1 BTHLM1/BTHLM2, UCMD1/UCMD2 Bethlem myopathy-1 and 2, Ullrich congenital muscular dystrophy-1 and 2
Dystroglycanopathy B3GALNT2, B4GAT1, DAG1, FKRP, FKTN, GMPPB, ISPD, LARGE1, POMGNT1, POMGNT2, POMK, POMT1, POMT2, RXYLT1 (formerly known as TMEM5) MDDGA1, MDDGA2, MDDGA3, MDDGA4, MDDGA5, MDDGA6, MDDGA7, MDDGA8, MDDGA9, MDDGA10, MDDGA11, MDDGA12, MDDGA13, MDDGA14, MDDGB1, MDDGB2, MDDGB3, MDDGB4, MDDGB5, MDDGB6, MDDGB14, MDDGC1, MDDGC2, MDDGC3, MDDGC4, MDDGC5, MDDGC7, MDDGC9, MDDGC12, MDDGC14 Walker-Warburg syndrome, Muscle-eye-brain disease, Fukuyama and Fukuyama-like muscular dystrophy, CMD with cerebellar involvement, CMD with intellectual disability, CMD without intellectual disability, LGMD with intellectual disability, LGMD without intellectual disability
Congenital disorders of glycosylation (CDG) DPM1, DPM2, DPM3 CDG1E, CDG1U, CDG1O CDG with abnormal alpha-dystroglycan glycosylation
Dystrophinopathies DMD N/A Duchenne/Becker muscular dystrophy
CHKB-related CMD CHKB N/A congenital weakness; cognitive impairment; pruritus; enlarged mitochondria found in muscle biopsy
Integrin alpha-7 deficiency ITGA7 N/A very rare; delayed motor milestones; walking within 2–3 years of life
Laminin alpha 2-deficiency LAMA2 MDC1A most common single gene to cause CMD; typically symptomatic at birth, with hypotonia and poor suck; in childhood, white matter abnormalities on brain imaging are common
LMNA-related CMD LMNA N/A dropped head syndrome; axial and scapuloperoneal involvement; absent or early loss of ambulation
Telethoninopathy TCAP LGMD2G typically has LGMD presentation, but may present in infancy with clinical features overlapping with mild forms of α-dystroglycanopathy

Mutation detection rate for CMDs in general ranges from 20% to 46%. The clinical sensitivity can also vary depending on the CMD subtype. In individuals with collagenopathies (Ullrich CMD or Bethlem myopathy), pathogenic variants in COL6A1, COL6A2, and COL6A3 account for the majority of cases. Pathogenic variants are identified in 30% to 66% of children with dystroglycanopathy. In Fukuyama CMD, FKTN mutations are detected in as many as 100% of individuals. In muscle-eye-brain disease, POMGNT1 mutations may be detected in 100% of individuals, while in Walker–Warburg syndrome, only 40% of individuals have mutations in the known genes. This panel also includes other genes that have been identified as causes of CMD, although the exact contribution of these genes to the overall detection rate is not known and is dependent on the clinical presentation of the individual.

CMD can be inherited in an autosomal dominant, autosomal recessive, or an X-linked pattern.

CMDs are thought to have penetrance approaching 100%. For some CMD genes, only a limited number of affected individuals have been described to date, making penetrance estimates difficult.

Prevalence estimates range from 0.68–2.5 per 100,000, although the incidence and prevalence of CMD in various populations are still being characterized and may have been initially underestimated in early published CMD studies due to more limited diagnostic studies. The relative frequency of individual types also varies in different populations. For example, Fukuyama muscular dystrophy is the most common CMD subtype in Japan due to a founder mutation in the FKTN gene. Laminin alpha-2 deficiency and type VI collagenopathies are the most common subtypes in many countries with populations of European origin.

The clinical spectrum of CMD is broad. 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.

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
B3GALNT2 NM_152490.4
B4GAT1 NM_006876.2
CHKB NM_005198.4
COL12A1 NM_004370.5
COL6A1 NM_001848.2
COL6A2 NM_001849.3
COL6A3 NM_004369.3
DAG1 NM_004393.5
DMD NM_004006.2
DPM1 NM_003859.1
DPM2 NM_003863.3
DPM3 NM_153741.1
FKRP NM_024301.4
FKTN NM_001079802.1
GMPPB NM_021971.2
ISPD NM_001101426.3
ITGA7 NM_002206.2
LAMA2 NM_000426.3
LARGE1 NM_004737.4
LMNA NM_170707.3
POMGNT1 NM_017739.3
POMGNT2 NM_032806.5
POMK NM_032237.4
POMT1 NM_007171.3
POMT2 NM_013382.5
RXYLT1 NM_014254.2
TCAP NM_003673.3