Background:
Myotonic dystrophy (DM) is a subtype of myopathy and the most common form of adult-onset muscular dystrophy. There are two major forms, distinguished by their clinical and molecular features: type I (DM1), also known as Steinert disease, and type II (DM2). DM1 is caused by the expansion of a CTG trinucleotide repeat that occurs in the 3’ untranslated region of the DMPK gene. Inheritance is autosomal dominant and newly expanded alleles have a bias for further expansions in successive generations causing more severe symptoms, a genetic phenomenon known as anticipation. Although anticipation typically occurs due to maternal transmission in the context of DM1, paternal transmission is possible and has been reported (Zeesman et al. 2002). DM1 is classically divided into three types: congenital, mild, and classic. Affected females are at risk for offspring with congenital myotonic dystrophy, characterized by severe hypotonia at birth, often with respiratory insufficiency and early death; intellectual disabilities is common (Meola and Cardani 2015).
Please note that antenatal findings of polyhydramnios and talipes (club foot) should prompt a search for maternal grip myotonia and if present definitive molecular testing for congenital DM1 should be considered in the fetus/newborn (Zaki et al. 2007).
Reasons for Referral:
- Diagnostic testing in symptomatic patient to confirm diagnosis
- Carrier testing in family
- Prenatal testing in an affected parent
Methodology:
Triplet repeat-primed PCR followed by size analysis using capillary electrophoresis to asses the CTG repeat in the 3’ untranslated region of the DMPK gene. CTG repeats >65 are reflexed to an alternate method determine the size of the repeat.
Reference Range:
Phenotype | #CTG Repeats |
Normal | <35 |
Premutation | 35-49 |
Affected (adult onset) Full Mutation | 50-1,000 (Mild 50-150; Classic 100-1,000) |
Affected (congenital) Full Mutation | >1,000 |
Specimen Requirements:
Blood: EDTA or ACD (Solution A or B):
- Adult: 5mL
- Child: 5mL
- Infant: 2-3mL
Saliva: 2 ORAgene Saliva Kits (OGR-500) used according to manufacturer instructions. Please contact KDL Client Services for a Saliva Collection Kit for patients that cannot provide a blood sample.
Assisted Saliva: 4 ORAgene Assisted Saliva Kits (OGR-575) used according to manufacturer instructions. Please contact KDL Client Services for an Assisted Saliva Collection Kit for patients that cannot provide a blood sample.
Buccal Cells: 4 CytoSoft™ Cytology Brush (Medical Packaging CYB-1) used according to manufacturer instructions. Please contact KDL Client Services for a Buccal Collection Kit for patients that cannot provide a blood sample.
- Please note that buccal samples may yield a limited amount of DNA, and additional specimens may be required for confirmatory or supplementary testing.
Skin Fibroblast: Punch Biopsy (Cell cultures will be prepared at KDL and used for testing), or 2 T-25 confluent flasks.
Prenatal:
- Direct Amniotic Fluid (10-20mL)
- Direct CVS
- Direct POC
- Cultured Amniocytes (2-T25 flasks)
- Cultured CVS (2-T25 flasks)
- Cultured Fetal Tissue: Product of Conception (2-T25 flasks)
- Cord Blood (1-2 mL)
DNA: 1-2µg at a minimum of 50-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS).
Notice Regarding Molecular Genetic Testing on Prenatal Specimens:Maternal cell rule-out testing will be performed on all prenatal specimens received. Please provide maternal blood (or saliva) in addition to the fetal specimen. Additional charges apply for the maternal cell rule-out test.
For routine testing of blood, saliva, and buccal swabs (or DNA extracted from them), KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion. For extraordinary circumstances, where testing must be performed within the above windows, please contact our lab.
REQUISITION FORM MUST ACCOMPANY ALL SAMPLES. Please include detailed clinical information, including ethnicity, clinical history, and family history.
Test Performed (Days):
Weekly
Turn Around Time:
14 – 21 Days
Shipment Sensitivity Requirements:
- Package and ship specimen to remain cold, but not frozen.
- Ship via overnight express, using the FedEx priority overnight label provided.
- Contact Client Services for shipping kits and instructions at (855) 535-1522.
References:
- Bird TD. Myotonic Dystrophy Type 1. 1999 Sep 17 [Updated 2024 Nov 14]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1165/
- Zeesman et al. Am J Med Genet. 2002;107(3):222-226. PMID: 11807903
- Meola and Cardani. Biochim Biophys Acta. 2015 Apr;1852(4):594-606. PMID: 24882752
- Zaki et al. Ultrasound Obstet Gynecol. 2007 Mar;29(3):284-8. PMID: 17238150
Additional Info:
Genetic counseling is indicated for individuals with a family history of DM.