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Congenital Myasthenic Syndrome via the MUSK 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
11477 MUSK 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11477MUSK81479 81479(x2) $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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

Congenital myasthenic syndromes (CMS) are disorders of the neuromuscular junction resulting from abnormalities of presynaptic, synaptic, or postsynaptic proteins. CMS are characterized by fatigable weakness affecting limb, ocular, facial, and bulbar muscles. Neonates present with feeding problems, choking, feeble cry, and muscle weakness. Patients presenting in later childhood are seen with abnormal exercise-induced fatigue and difficulty running. Most patients present prior to 2 years of age although rare exceptions are reported (eg. Croxen et al. Neurol 59:162-168, 2002). Symptoms are extremely variable and are in some case induced by febrile illness, infection, or excitement (eg. Byring et al. Neuromuscul Disord 12:548-553, 2002). Life-threatening respiratory crises may occur in affected neonates or older children. CMS may be differentiated from myasthenia gravis, an acquired autoimmune disorder, by earlier age of onset and by negative serology tests for anti-acetylcholine receptor (AchR) and anti-MuSk antibodies. One sibship with CMS and variants in the muscle specific tyrosine kinase (MUSK) gene has been reported (Chevessier et al. Hum Molec Genet 13:3229-3240, 2004). Symptoms of hypotonia, respiratory distress, vocal cord paralysis, and ptosis were present congenitally, and tracheostomies were performed. During childhood and adolescence one sibling experienced exercise-induced fatigue and ptosis, but overall, the course improved with no severe respiratory distress. Symptoms worsened during this patient’s pregnancy. The second patient died in early childhood (Chevessier et al. 2004). Evaluation of a muscle biopsy revealed severe deficiencies in MUSK and CHRNE gene products and remarkable structural abnormalities of the neuromuscular junction.

Genetics

Abnormalities of proteins involved with neuromuscular transmission underlie CMS, limb girdle CMS, Pena-Shokeir syndrome, and multiple pterygium syndromes. These disorders, which may represent a phenotypic continuum of a single entity, are most often inherited in an autosomal recessive manner. Post synaptic CMS with AChR deficiency (OMIM 608931) is inherited as an autosomal recessive condition and, rarely, is secondary to variants in the MUSK gene (OMIM 601296). The siblings reported by Chevessier et al. (2004) had one null and one missense variant.

The muscle-specific tyrosine kinase is encoded by exons 1 – 15 of the MUSK gene located on chr 9q31.

Clinical Sensitivity - Sequencing with CNV PGxome

Sensitivity for CMS testing is at least 50% overall; 30% for CHRNE, 10% for RAPSN, and 7.5% for COLQ (GeneReviews, Abicht and Lochmüller, 2006). CMS due to MUSK variants is probably a rare disease.

Testing Strategy

This test provides full coverage of all coding exons of the MUSK gene 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 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

A comprehensive diagnostic algorithm can be found in (GeneReviews, Abicht and Lochmüller, 2006). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in MUSK.

Gene

Official Gene Symbol OMIM ID
MUSK 601296
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Angela Abicht, Hanns Lochmuller (2006). "Congenital Myasthenic Syndromes."
  • Byring RF, Pihko H, Tsujino A, Shen XM, Gustafsson B, Hackman P, Ohno K, Engel AG, Udd B. 2002. Congenital myasthenic syndrome associated with episodic apnea and sudden infant death. Neuromuscul Disord 12: 548-553. PubMed ID: 12117478
  • Chevessier, F., et.al. (2004). "MUSK, a new target for mutations causing congenital myasthenic syndrome." Hum Mol Genet 13(24): 3229-40. PubMed ID: 15496425
  • Croxen R, Hatton C, Shelley C, Brydson M, Chauplannaz G, Oosterhuis H, Vincent A, Newsom-Davis J, Colquhoun D, Beeson D. 2002. Recessive inheritance and variable penetrance of slow-channel congenital myasthenic syndromes. Neurology 59: 162-168. PubMed ID: 12141316

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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