myotonic dystrophy type 1

Myotonic dystrophy type 1, also known as Steinert disease, is a multisystem muscle disorder primarily characterized by myotonia and progressive muscle weakness, along with cardiac, ocular, and endocrine involvement. It is caused by a CTG repeat expansion in the DMPK gene, leading to dynamic changes in gene expression. The condition typically presents in adulthood, although severe congenital forms can occur with maternal transmission. It affects approximately 1 in 8,000 individuals worldwide, and severity can vary widely between affected individuals.

The clinical presentation of myotonic dystrophy type 1 is marked by several characteristic features. Most affected individuals experience myotonia, where there is a delayed relaxation of muscles after contraction, and progressive muscle weakness that is more pronounced in distal muscles. Other common features include posterior subcapsular cataracts, cardiac conduction abnormalities, and excessive daytime sleepiness, often accompanied by respiratory difficulties that necessitate monitoring. Cognitive impairment and atypical behavioral changes are observed in a subset of patients, highlighting the involvement of the central nervous system. Not all individuals experience all features, and severity varies considerably.

Myotonic dystrophy type 1 is caused by an abnormal CTG repeat expansion in the 3' untranslated region of the DMPK gene. In unaffected individuals, the repeat is typically in the range of 5 to 34 copies, whereas affected individuals may have 50 to thousands of repeats. This repeat expansion is a dynamic mutation and can change in size when passed from one generation to the next, a phenomenon that may contribute to anticipation, where symptoms can appear earlier or more severely in subsequent generations. The condition is inherited in an autosomal dominant manner, meaning that a single altered copy of the gene can result in disease, and while de novo expansions are rare, genetic counseling is recommended for family planning.

Currently, management of myotonic dystrophy type 1 focuses on supportive care and symptom management, with treatment tailored to the individual. Foundational therapies include regular cardiac evaluations such as annual electrocardiograms and Holter monitoring; pacemaker or ICD placement may be necessary for significant conduction abnormalities. Therapeutic measures also address myotonia with medications like mexiletine and manage excessive daytime sleepiness with agents such as modafinil, while respiratory monitoring and BiPAP use can be critical in cases of respiratory insufficiency. Surgical intervention for cataracts is performed when visual impairment is significant. Overall, care is delivered by a multidisciplinary team including neurologists, cardiologists, pulmonologists, ophthalmologists, and genetic counselors, and patients should discuss treatment options with their healthcare team to determine what is most appropriate for their situation.

The outlook for individuals with myotonic dystrophy type 1 is variable, with disease progression differing widely between individuals. Some patients experience a gradual worsening of muscle weakness and cardiac complications over time, while others may have periods of relative stability. With current standards of care, many individuals maintain a good quality of life into adulthood, and outcomes described in medical literature continue to evolve as standards of care improve. Given the variability in symptom severity and progression, ongoing multidisciplinary care and regular surveillance are key, and families are encouraged to seek genetic counseling and support group resources to better understand and manage the condition.

Myotonic dystrophy type 1 is an active area of research, with numerous ongoing clinical trials investigating potential therapies such as antisense oligonucleotide treatments, CRISPR-based approaches, and small molecule splicing modulators targeting toxic RNA. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.