Congenital Muscular Dystrophy (CMD) Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10379 B3GALNT2 81479,81479 Order Options and Pricing
B4GAT1 81479,81479
CHKB 81479,81479
COL12A1 81479,81479
COL6A1 81407,81479
COL6A2 81407,81406
COL6A3 81407,81479
CRPPA 81405,81479
DAG1 81479,81479
DMD 81408,81161
DPM1 81479,81479
DPM2 81479,81479
DPM3 81479,81479
EMD 81405,81404
FKRP 81404,81479
FKTN 81405,81479
GMPPB 81479,81479
ITGA7 81479,81479
LAMA2 81408,81479
LARGE1 81479,81479
LMNA 81406,81479
POMGNT1 81406,81479
POMGNT2 81479,81479
POMK 81479,81479
POMT1 81406,81479
POMT2 81406,81479
RXYLT1 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10379Genes x (27)81479 81161, 81404, 81405, 81406, 81407, 81408, 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

The congenital muscular dystrophies are a clinically and genetically heterogeneous group of disorders characterized by elevated serum CK levels, muscle weakness, a dystrophic process observed in biopsied muscle, and variable associated findings such as central nervous system abnormalities, cardiac muscle involvement, skeletal effects, and developmental delay (Bertini et al. 2011). Onset of symptoms generally occurs at birth, although some symptoms do not manifest until later in life. This panel includes testing for Merosin-deficient congenital muscular dystrophy, dystroglycanopathies including Walker-Warburg syndrome (WWS), Ullrich congenital muscular dystrophy, Bethlem myopathy, dystrophinopathies, Emery-Dreifuss muscular dystrophy, LMNA-related muscular dystrophies, and other rare forms of muscular dystrophy.

Genetics

Congenital muscular dystrophies caused by pathogenic variants in LAMA2, CHKB, ITGA7, B3GALNT2 , B4GAT1, CRPPA/ISPD, DAG1 , DPM1, DPM2, DPM3, FKRP, FKTN, GMPPB, LARGE1, POMGNT1, POMGNT2, POMK, POMT1, POMT2, and RXYLT1/TMEM5 are inherited in an autosomal recessive manner. Pathogenic variants in these genes include missense, nonsense, splicing, and small deletions/insertions (http://www.dmd.nl/; Human Gene Mutation Database). Gross deletions/duplications have been commonly reported in the CRPPA/ISPD, LAMA2, and LARGE1 genes (Human Gene Mutation Database). LMNA related congenital muscular dystrophy is inherited as autosomal dominant disorder and many times occurs as a result of de novo mutation.

DMD and EMD both cause X-linked recessive muscular dystrophies. Approximately two-thirds of the pathogenic variants in Duchenne muscular dystrophy patients are deletions of one or more exons in the DMD gene. The occurrence of deletions is slightly higher in Becker muscular dystrophy patients. Duplications are found in approximately 10% of Duchenne muscular dystrophy patients and 20% of Becker muscular dystrophy patients. Pathogenic variants detectable by sequence analysis are found in approximately one-third of Duchenne muscular dystrophy cases and in approximately 20% of Becker muscular dystrophy cases. Emery-Dreifuss muscular dystrophy is caused by pathogenic variants in the EMD gene which include missense, nonsense, and splicing variants and also small out-of-frame insertions/deletions and gross deletions (Human Gene Mutation Database).

Most cases of Bethlem myopathy have autosomal dominant inheritance of COL6A1, COL6A2 or COL6A3 pathogenic variants (Lampe and Bushby 2005; Jobsis et al. 1999; Butterfield et al. 2013). Once thought to be strictly a recessive condition, Ullrich congenital muscular dystrophy has been shown to be inherited in a dominant manner in numerous cases (Pan et al. 2003). A dominant-negative effect underlies pathogenicity of dominantly inherited UCMD (Pan et al. 2003; Baker et al. 2005), while most cases of recessive UCMD result from truncating pathogenic variants. Recently, both dominant and recessive pathogenic variants in a fourth collagen gene, COL12A1, have been found in patients with Ullrich and Bethlem phenotypes (Hicks et al. 2014; Zou et al. 2014).

Clinical Sensitivity - Sequencing with CNV PGxome

Because of extensive phenotypic and locus heterogeneity for the congenital muscular dystrophies, over-all clinical sensitivity is difficult to estimate. Based on results from both the literature and PreventionGenetics, we estimate that this test will detect pathogenic variants in roughly 45% of patients (Sparks et al. 2012). Pathogenic variants in LAMA2, which cause merosin-deficient CMD, are over-all the most common subtype of CMD. In one study (Allamad et al. 2002) merosin-deficient CMD was found to account for about 30% of the CMD cases in Europe. In a cohort of ninety fetuses with severe cobblestone lissencephaly and associated findings consistent with Walker-Warburg syndrome, Vuillaumier-Barrot et al (2012), found a genetic diagnosis in 58, or 64%. These diagnosed cases had relative frequencies as follows: POMT1 (42%), POMT2 (17%), POMGNT1 (17%), CRPPA/ISPD (9%), RXYLT1/TMEM5 (9%), LARGE1 (3%) and FKRP (3%). Sequence analysis using genomic DNA from peripheral blood was found to have clinical sensitivity of 66%, 56%, and 79% among patients classified as having typical Bethlem Myopathy, severe Bethlem Myopathy, and Ulrich Congenital Muscular Dystrophy, respectively (Lampe et al. 2005).

Clinical sensitivity of deletion/duplication testing for most of the CMD genes is low, except for the CRPPA/ISPD, DMD, LAMA2 and LARGE1 genes (Human Gene Mutation Database). Approximately two-thirds of the pathogenic variants in Duchenne muscular dystrophy patients are deletions of one or more exons in the DMD gene. The occurrence of deletions is slightly higher in Becker muscular dystrophy patients. Duplications are found in approximately 10% of Duchenne muscular dystrophy patients and 20% of Becker muscular dystrophy patients.

Testing Strategy

This panel typically provides ≥98% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Elevated serum CK at birth or early in life and/or muscle biopsy consistent with dystrophic process. This test especially aids in a differential diagnosis of similar phenotypes, rules out particular syndromes, and provides the analysis of multiple genes simultaneously.

Diseases

Name Inheritance OMIM ID
Becker Muscular Dystrophy XL 300376
Bethlem Myopathy AR, AD 158810
Bethlem Myopathy 2 AR, AD 616471
Congenital Disorder Of Glycosylation Type 1E AR 608799
Congenital Disorder Of Glycosylation Type 1O AR 612937
Congenital Disorder of Glycosylation Type Iu AR 615042
Congenital Muscular Dystrophy-Dystroglycanopathy (With Brain And Eye Anomalies) Type A5 AR 613153
Duchenne Muscular Dystrophy XL 310200
Emery-Dreifuss Muscular Dystrophy 1, X-Linked XL 310300
Fukuyama Congenital Muscular Dystrophy AR 253800
Merosin Deficient Congenital Muscular Dystrophy AR 607855
Muscle Eye Brain Disease AR 253280
Muscular Dystrophy, Congenital, Due To Integrin Alpha-7 Deficiency AR 613204
Muscular Dystrophy, Congenital, LMNA-Related AR, AD 613205
Muscular Dystrophy, Congenital, Megaconial Type AR 602541
Muscular Dystrophy-Dystroglycanopathy (Congenital with Brain and Eye Anomalies), Type A, 10; MDDGA10 AR 615041
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 AR 615249
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 AR 615287
Muscular Dystrophy-Dystroglycanopathy (Congenital With Brain And Eye Anomalies), Type A, 6 AR 613154
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 AR 614643
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 11 AR 615181
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 AR 615352
Muscular Dystrophy-Dystroglycanopathy (Limb-Girdle), Type C, 2 AR 613158
Muscular Dystrophy-Dystroglycanopathy (Limb-Girdle), Type C, 9 AR 613818
Ullrich Congenital Muscular Dystrophy AR, AD 254090
Ullrich Congenital Muscular Dystrophy 2 AR, AD 616470
Walker-Warburg Congenital Muscular Dystrophy AR, AD 236670

Related Test

Name
PGxome®

Citations

  • Allamand V., Guicheney P. 2002. European Journal of Human Genetics. 10: 91-4. PubMed ID: 11938437
  • Baker N.L. et al. 2005. Human Molecular Genetics. 14: 279-93. PubMed ID: 15563506
  • Bertini E. et al. 2011. Seminars in Pediatric Neurology. 18: 277-88. PubMed ID: 22172424
  • Butterfield R.J. et al. 2013. Human Mutation. 34: 1558-67. PubMed ID: 24038877
  • Hicks D. et al. 2014. Human Molecular Genetics. 23: 2353-63. PubMed ID: 24334769
  • Human Gene Mutation Database (Bio-base).
  • Jöbsis G.J. et al. 1999. Brain : a Journal of Neurology. 122 ( Pt 4): 649-55. PubMed ID: 10219778
  • Lampe A.K. et al. 2005. Journal of Medical Genetics. 42: 108-20. PubMed ID: 15689448
  • Lampe A.K., Bushby K.M. 2005. Journal of Medical Genetics. 42: 673-85. PubMed ID: 16141002
  • Pan T.C. et al. 2003. American Journal of Human Genetics. 73: 355-69. PubMed ID: 12840783
  • Sparks S. et al. 2012. Congenital Muscular Dystrophy Overview. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301468
  • Vuillaumier-Barrot S. et al. 2012. American Journal of Human Genetics. 91: 1135-43. PubMed ID: 23217329
  • Zou Y. et al. 2014. Human Molecular Genetics. 23: 2339-52. PubMed ID: 24334604

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

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