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Myotonic dystrophy type 2
DM2 is a hereditary disorder characterised by muscle weakness, stiffness (myotonia), and sometimes cataracts or heart problems. It typically emerges in adulthood and affects multiple body systems.
Overview
Myotonic dystrophy type 2 (DM2) is a form of muscular dystrophy, a group of conditions that cause progressive muscle weakness and wasting. Unlike some other muscular dystrophies, DM2 often involves other body systems in addition to the muscles [PMID:24097480]. Symptoms typically begin in adulthood, and the condition can vary significantly in its severity and presentation among affected individuals.
DM2 is estimated to affect around 1 in 8,000 people in Europe, although the exact prevalence may be higher due to underdiagnosis. It is a lifelong condition, and management focuses on addressing symptoms and improving quality of life.
Symptoms & clinical features
The primary symptoms of DM2 involve the muscles. Myotonia, a delayed relaxation of muscles after contraction, is a hallmark feature. This can cause difficulty releasing a handshake or lead to muscle stiffness, especially after exercise or in cold temperatures. Muscle weakness is often experienced in the neck, hip, and shoulder muscles, which can lead to problems with daily activities such as climbing stairs or lifting objects [PMID:30132334].
Beyond muscle-related symptoms, individuals with DM2 may develop cataracts, which are clouding of the eye's lens. Heart conduction problems, insulin resistance, and sometimes problems with cognitive function or mood changes can also occur. The severity and combination of these symptoms can differ greatly from person to person, even within the same family.
Video: Genetics 101
Affected organs
DM2 primarily affects the skeletal muscles, leading to myotonia and progressive weakness. The heart can also be involved, with potential for abnormalities in its electrical conduction system that may necessitate monitoring. The eyes are frequently affected, typically by the development of cataracts.
Other body systems that may experience involvement include the endocrine system, which can result in insulin resistance, and occasionally the central nervous system, leading to cognitive or behavioural changes. The skin may also show changes, such as patches of dry skin or increased sweating in certain areas.
Risks & severity
The severity of DM2 can range from mild, with primarily muscle stiffness and minor weakness, to more severe forms impacting mobility and daily function. Symptoms typically emerge in adulthood, often between the ages of 30 and 50, although onset can vary. It is a progressive condition, meaning symptoms may worsen over time.
The lifetime risks associated with DM2 include potential cardiac complications, which can be serious and may require regular heart monitoring. Cataracts are very common and often appear earlier than in the general population. While muscle weakness can lead to reduced mobility, life expectancy is generally not significantly shortened in most individuals with DM2, unlike some other forms of muscular dystrophy.
Genetic causes
Myotonic dystrophy type 2 is caused by an expansion of a specific section of DNA within the CNBP gene [PMID:24097480]. The CNBP gene provides instructions for making a protein involved in regulating other genes and maintaining genomic stability. In DM2, a repetitive segment of DNA within this gene, known as a CCTG repeat, becomes abnormally long.
This expanded repeat does not directly affect the function of the CNBP protein. Instead, the abnormally long RNA molecule produced from the altered gene gets trapped in the cell's nucleus. These trapped RNA molecules then interfere with the function of other proteins, preventing them from carrying out their normal roles in various cells and tissues, particularly muscle cells. This 'toxic RNA' mechanism leads to the diverse symptoms observed in DM2.
- CNBP CCHC-type zinc finger nucleic acid binding protein
Inheritance pattern
Myotonic dystrophy type 2 is inherited in an autosomal dominant pattern. This means that a person only needs to inherit one copy of the altered CNBP gene from a parent to develop the condition. If a parent has DM2, each of their children has a 50% chance of inheriting the expanded gene and developing the condition.
The condition can sometimes show anticipation, where symptoms may start earlier and be more severe in successive generations within a family. This is due to the CCTG repeat expansion sometimes becoming even longer when passed from parent to child.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
A diagnosis of DM2 is typically suspected based on clinical symptoms such as myotonia, muscle weakness, and the presence of cataracts. Confirmation of the diagnosis requires genetic testing to identify the CCTG repeat expansion in the CNBP gene. This testing is usually performed on a blood sample.
Referral for genetic testing often comes from a neurologist or clinical geneticist. In the UK, genetic testing for DM2 falls under the NHS Genomic Medicine Service, and an R-code, such as R86 Myotonic Dystrophy, would be relevant for this diagnostic pathway. Genetic counselling is an important part of the diagnostic process, offering support and information to individuals and families.
Management & lifestyle
There is currently no cure for DM2, so management focuses on alleviating symptoms and preventing complications. A multidisciplinary team, which may include neurologists, cardiologists, ophthalmologists, physiotherapists, and genetic counsellors, often provides care. Regular monitoring for heart problems and cataracts is crucial, as these can be managed through medication, pacing, or surgery respectively.
Physiotherapy can help maintain muscle strength and flexibility, and occupational therapy can provide strategies to assist with daily activities. Lifestyle modifications, such as regular exercise (adapted to individual capacity) and avoiding cold exposure which can worsen myotonia, may be beneficial. Genetic counsellors can provide essential support, information about the condition, inheritance patterns, and family planning options within the NHS framework.
UK care pathway
In the UK, individuals with suspected genetic conditions like Myotonic Dystrophy Type 2 are typically referred to a clinical genetics service or specialist neurology clinic. These services operate within the NHS Genomic Medicine Service (GMS). Genetic testing, often guided by specific R-codes from the National Genomic Test Directory (e.g., R86 Myotonic Dystrophy), is performed to confirm a diagnosis.
Following a diagnosis, individuals are usually offered access to genetic counselling. This service provides information about the condition, its inheritance, and implications for family members. Management plans are developed by specialist teams, aiming to address specific symptoms and monitor for complications.
Frequently asked questions
What is the difference between Myotonic Dystrophy type 1 and type 2?
Both types cause muscle weakness and stiffness (myotonia), but they are caused by different genetic changes and can have different patterns of muscle involvement and other symptoms. DM1 is generally more severe and can have earlier onset than DM2.
Can DM2 be passed on to children?
Yes, DM2 is inherited in an autosomal dominant pattern. This means if you have DM2, each of your children has a 50% chance of inheriting the genetic change and developing the condition.
Are there treatments for Myotonic Dystrophy type 2?
While there isn't a cure, treatments focus on managing symptoms and complications. This can include physiotherapy, medication for myotonia, monitoring for heart issues, and cataract surgery. A multidisciplinary team approach helps manage the condition effectively.
How does DM2 affect daily life?
DM2 can affect daily life through muscle weakness and stiffness, impacting activities like walking, lifting, and grasping. Other symptoms like fatigue, cataracts, and heart problems can also influence quality of life. The impact varies greatly among individuals.
Will my symptoms get worse over time?
DM2 is a progressive condition, meaning symptoms may gradually worsen over time. However, the rate of progression and the severity of symptoms can vary significantly between individuals. Regular medical check-ups help monitor the condition.
References
- Hamel JI. Myotonic Dystrophy. Continuum (Minneapolis, Minn.). 2022. PMID: 36537977
- Huang CC, Kuo HC. Myotonic dystrophies. Chang Gung medical journal. 2005. PMID: 16265841
- Liao Q, Zhang Y, He J. Global Prevalence of Myotonic Dystrophy: An Updated Systematic Review and Meta-Analysis. Neuroepidemiology. 2022. PMID: 35483324
- Johnson NE. Myotonic Muscular Dystrophies. Continuum (Minneapolis, Minn.). 2019. PMID: 31794466
- Salort-Campana E, Attarian S. Late-onset myopathies. Current opinion in neurology. 2024. PMID: 39017649
- Meola G. Myotonic dystrophies. Current opinion in neurology. 2000. PMID: 11073357
- Jain A, Al Khalili Y. Congenital Myotonic Dystrophy. 2023. PMID: 32809353
- Kleefeld F, Horvath R, Pinal-Fernandez I. Multi-level profiling unravels mitochondrial dysfunction in myotonic dystrophy type 2. Acta neuropathologica. 2024. PMID: 38240888