No genes are listed in the packet for this entry, and no inheritance pattern is recorded in the packet's inheritance field, so the genetic basis is not certified here at the level of this broader entry. The packet definition describes an inherited disorder. For DM1 specifically, GeneReviews describes a CTG trinucleotide repeat expansion. It reports normal alleles of 5 to 34 CTG repeats, mutable normal (premutation) alleles of 35 to 49 repeats, and full-penetrance alleles of 50 or more repeats, and states that individuals with premutation-range expansions have not been reported to have symptoms, although their children are at increased risk of inheriting a larger repeat. GeneReviews describes DM1 as inherited in an autosomal dominant manner and describes the expanded allele as able to lengthen further during transmission, which may be associated with earlier onset and more severe disease in the next generation. It states that repeat size generally correlates with phenotype category but that the ranges overlap considerably, so repeat size is not used to predict disease severity. The causes of the other subtypes listed in the packet are not certified in this packet.

The packet does not list diagnostic methods for this entry. GeneReviews describes the diagnostic approach for DM1. It states that DM1 is suspected in adults with muscle weakness, myotonia, and posterior subcapsular cataracts detectable on slit lamp examination, and in neonates with hypotonia, facial weakness, generalized weakness, positional malformations, or respiratory insufficiency. According to GeneReviews, the diagnosis of DM1 is established by molecular genetic testing identifying a pathogenic expansion, with targeted analysis for an increased number of CTG repeats, and a panel including nucleotide repeat analysis and other non-sequencing-based tests may be used to identify the cause. Reference allele-size ranges were established by the Second International Myotonic Dystrophy Consortium in 1999 according to GeneReviews. Genetic confirmation procedures for the other subtypes are not certified in this packet.

No FDA-approved treatment is certified in this packet. The orphan drug record in the packet, mecasermin from Insmed, Inc. for treatment of myotonic dystrophy, carries DESIGNATED status, which does not indicate approval. The packet lists no foundational therapies. GeneReviews management content for DM1 states that no specific treatment exists for the progressive weakness, and that management guidelines have been developed. GeneReviews describes evaluation of the need for ankle-foot orthoses, wheelchairs, or other assistive devices by physiatry, occupational therapy, or physical therapy as the disease progresses, orthopedic surgery for musculoskeletal deformities in children, and special education support for children. It describes myotonia as typically mild to moderate and rarely requiring treatment, with anecdotal responses to mexiletine or carbamazepine in some individuals. For pain, GeneReviews states that different medications and combinations work for some individuals but none has been routinely effective. It describes cataract removal when vision is impaired, cardiology involvement for individuals with cardiac symptoms or arrhythmia on EKG, and hormone replacement for symptomatic males with low serum testosterone. GeneReviews also lists initial evaluations across neurologic, ophthalmologic, cardiovascular, respiratory, endocrine, gastrointestinal, and surgical or anesthesia concerns, which indicates a multisystem, multidisciplinary approach in that chapter.

A natural history record is not certified in this packet. GeneReviews describes DM1 as a continuum from mild to severe. It reports an average age of death of 60 years to a normal life span for the mild phenotype, 48 to 55 years for the classic phenotype, and 45 years for the congenital phenotype, with the congenital figure excluding neonatal deaths. GeneReviews also states that fatal arrhythmias can occur before other symptoms in individuals with DM1, and that some strength may return when hypothyroidism or certain cholesterol-lowering medications are identified as contributing to increased weakness. These figures describe groups in the GeneReviews DM1 chapter and are not certified for other subtypes of myotonic dystrophy in this packet.

Active clinical trials for this condition are listed on ClinicalTrials.gov, and the packet records numerous active studies. Records in the packet include a recruiting Phase 3 study of zeleciment basivarsen (DYNE-101) in myotonic dystrophy type 1 sponsored by Dyne Therapeutics, a recruiting Phase 3 study of once daily mexiletine PR in myotonic dystrophy type 1 and type 2 sponsored by Lupin Ltd., a recruiting Phase 1 gene therapy study (SAR446268) in non-congenital myotonic dystrophy type 1 sponsored by Sanofi, a recruiting Phase 2 study of PGN-EDODM1 sponsored by PepGen Inc, and a Phase 1/2 study of VX-670 sponsored by Vertex Pharmaceuticals with active, not recruiting status. Additional records are biomarker and endpoint studies in myotonic dystrophy type 1 sponsored by Virginia Commonwealth University. The packet's trial summary lists drug therapy, medical device, procedural, and other interventions among the intervention types and indicates that gene therapy trials are present.