Congenital Myopathy with Diaphragmatic Defects, Respiratory Insufficiency, and Dysmorphic Facies via the MYOD1 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
13307 MYOD1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
13307MYOD181479 81479(x2) $890 Order Options and Pricing

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

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

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Fetal akinesia (FA) describes a clinical syndromic entity characterized by reduced or absent fetal movements resulting in multiple phenotypic abnormalities. These secondary defects may include intrauterine growth restriction (IUGR), craniofacial dysmorphic features (cleft palate or retromicrognathia), limb pterygia, pulmonary hypoplasia, and arthrogryposis. This group of disorders contains several overlapping conditions ranging from distal arthrogryposis, multiple pterygium syndrome, arthrogryposis multiplex congenita (AMC), to the more severe lethal congenital contracture syndrome and fetal akinesia deformation sequence (FADS) (Beecroft et al. 2018. PubMed ID: 29959180; Pergande et al. 2020. PubMed ID: 31680123). 

AMC is defined by congenital, non-progressive contractures in more than two joints and in multiple body areas. These contractures and reduced fetal movement can lead to secondary polyhydramnios or fetal hydrops. The underlying defect can be genetic or environmental. Causes can include muscle disorders, neurological disorders, connective tissue disorders, fetal vascular compromise, uterine space limitations, and maternal disease or drug use. The overall incidence of AMC ranges from 1/3,000 to 1/5,000 live births (Beecroft et al. 2018. PubMed ID: 29959180; Pergande et al. 2020. PubMed ID: 31680123). 

Congenital myopathy with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies was first reported in a consanguineous family in which three neonates from two sibships presented with lethal fetal akinesia, cleft palate, and arthrogryposis (Watson et al. 2016. PubMed ID: 26733463). In an additional patient with a homozygous nonsense variant, a less severe course was described. This patient presented with respiratory infections, hypotonia, ptosis, motor delay, failure to thrive and diaphragm musculature being severely affected (Lopes et al. 2018. PubMed ID: 30403323). In another family, two siblings homozygous for a frameshift variant presented with motor delays, poor weight gain, triangular face, pectus excavatum, and distal arthrogryposis (Shukla et al. 2019. PubMed ID: 31260566). This indicates there is likely phenotypic variability from severe fetal akinesia to a more mild congenital myopathy. Genetic testing may aide in establishing a differential diagnosis and may assist reproductive planning.

Genetics

Pathogenic variants in MYOD1 are associated with autosomal recessive congenital myopathy with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies. To date, only nonsense variants and one small duplication resulting in a frameshift variant have been reported to be causative (Watson et al. 2016. PubMed ID: 26733463; Lopes et al. 2018. PubMed ID: 30403323; Shukla et al. 2019. PubMed ID: 31260566).  All pathogenic variants have been inherited from a carrier parent. No structural variants have been reported.

MYOD1 encodes myogenic differentiation antigen 1, which is exclusively expressed in skeletal muscle. MYOD1 belongs to a family of transcription factors that are essential for myogenic differentiation and repair. A MyoD knockout mouse is viable, fertile, and produces offspring that do not exhibit overt muscle abnormalities. However, a double knockout of MyoD and Myf-5 created a lethal phenotype with complete absence of skeletal muscle indicating these two genes may have some functional redundancy (Rudnicki et al. 1992. PubMed ID: 1330322). MYOD1 has been cited as a non-essential gene for growth of human tissue culture cells (Online Gene Essentiality).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity is difficult to estimate, as to date, a limited number of cases have been described in the literature (Watson et al. 2016. PubMed ID: 26733463; Lopes et al. 2018. PubMed ID: 30403323; Shukla et al. 2019. PubMed ID: 31260566). Analytical sensitivity should be high as all pathogenic variants reported to date are detectable by sequencing.

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the MYOD1 gene plus 10 bases flanking noncoding DNA in all available transcripts in addition to non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as ≥20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Candidates for this test are patients with clinical features consistent with a diagnosis of fetal akinesia or congenital myopathy with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies. Targeted testing is indicated for family members of patients who have known pathogenic variants in MYOD1. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in MYOD1.

Gene

Official Gene Symbol OMIM ID
MYOD1 159970
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Beecroft et al. 2018. PubMed ID: 29959180
  • Lopes et al. 2018. PubMed ID: 30403323
  • Online Gene Essentiality (OGEE).
  • Pergande et al. 2020. PubMed ID: 31680123
  • Rudnicki et al. 1992. PubMed ID: 1330322
  • Shukla et al. 2019. PubMed ID: 31260566
  • Watson et al. 2016. PubMed ID: 26733463

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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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