What is myotonic dystrophy?
Myotonic dystrophy (often abbreviated to DM after its Latin name dystrophia myotonica) exists in two forms: Type 1 (DM1) and Type 2 (DM2). Both conditions are genetic disorders, but each one is caused by mutations in different genes. Myotonic dystrophy is thought to affect at least 1 in 8,000 people worldwide.
Type 1 myotonic dystrophy (DM1), also called Steinert’s disease, causes muscle wasting and weakness. However, it also affects many other systems in the body and this multi-systemic/multi-organ involvement is a particular feature of myotonic dystrophy. In some cases, the non-muscle-related features of the condition – especially the heart problems – can be more of an issue for patients than muscle weakness or myotonia.
The genetic change that causes the symptoms of myotonic dystrophy is present at birth, but depending on its severity, symptoms of myotonic dystrophy may become noticeable at almost any age. The disease is often categorised according to age of onset: adult-onset (‘classical’ form), congenital and childhood-onset.
Type 2 myotonic dystrophy (DM2), also sometimes called ‘PROMM’ (proximal myotonic myopathy), does not have a congenital or childhood-onset form – it is only found in adults, with an age of onset generally between 30 and 60 years.
What causes myotonic dystrophy?
DM1 is inherited in an autosomal dominant pattern and is caused when a certain segment of DNA at the end of a gene called DMPK is repeated abnormally, forming an unstable region within the gene. This is called a triplet repeat expansion. Unaffected individuals have a small number of repeats (up to about 35); in affected individuals the number can be much higher – rising to several thousand in children living with congenital DM.
There is some correlation between the number of repeats and the severity of the disease, although individuals with a similar repeat count may be quite differently affected. There is also a correlation between number of repeats and age of onset, and a noticeable feature of myotonic dystrophy is that the number of repeats tends to increase in each successive generation – so a grandparent (slightly increased repeat count) might experience their first mild symptoms at age 60, while their children (moderately increased repeat count) notice symptoms at 30, and grandchildren (massively increased repeat count) may be congenitally affected. This phenomenon is known as “anticipation”.
DM2 is also caused by a repeat expansion in a segment of DNA, however, the mutation is found in the CNBP gene – a different gene to that affected in DM1. DM2 is also inherited in an autosomal dominant pattern and is more common in some geographical regions than others. Anticipation does not appear to be a characteristic of this type of myotonic dystrophy.
What are the signs and symptoms of myotonic dystrophy?
Myotonic Dystrophy causes weakness of the voluntary muscles, although the degree of weakness and the muscles affected differs according to type of DM and the age of the patient. Myotonia (difficulty in relaxing muscles), is another feature of DM and as the disease progresses, the muscles of the heart and those used for breathing can be affected.
In DM1, the involuntary muscles such as those in the gastrointestinal tract can also be affected, and difficulty swallowing or problems with the bowel can occur. In females, the muscles in the womb can behave abnormally, leading to complications in pregnancy and labour. Other symptoms can also include cataracts, heart conduction defects and endocrine changes including diabetes.
In congenital DM1, may have problems with breathing and swallowing and, in severe cases, may need respiratory support and a feeding tube from birth. However, unlike some other forms of muscular dystrophy, infants who overcome initial problems with breathing and feeding can make progress and achieve motor milestones. There can also be impairment of cognitive functioning and these children may also have problem with speech, hearing, and vision fatigue.
In DM2, symptoms are often relatively milder and have a slower progression. In DM2, weakness usually affects the proximal muscles (those closest to the body), and it is quite common for DM2 patients to experience muscle pain. Only a minority of patients have cataracts and some patients may experience heart conduction defects and diabetes.
How does the disease progress?
As with most neuromuscular diseases, the progression of myotonic dystrophy varies greatly from person to person but in the classical adult-onset form of DM1 and DM2, symptoms generally progress gradually. When DM1 begins in early life, it may be very different in progression to the adult-onset form and children may display cognitive impairment, delayed speech and other developmental delays.
Although no cure for myotonic dystrophy exists at present, adequate care and support can do a lot to help those living with the condition. Many doctors are unfamiliar with the condition, and this makes it particularly important that people who have myotonic dystrophy and their families are aware of the problems they may face to ensure effective management of the disease.