Inheritance: Autosomal Dominant Genetic Alteration: Dystrophia Myotonica Protein Kinase
Gene (DMPK) on Chromosome 19: CTG trinucleotide repeat Incidence: 1 in 20,000 people are affected Onset: congenital through adulthood Muscles Affected: Voluntary (distal) muscles of limbs
and the neck, facial, and diaphragm muscles,intercostal muscles,
possibly the cardiac muscle, birthing muscles. Other Symptoms: cataracts, diabetes, complications
with anesthesia, potential for mental retardation
The myotonic disorders are a heterogeneous group of conditions
that share the common feature of myotonia; delayed muscular
relaxation associated with a characteristic pattern of repetitive
electrical discharges (P.S. Harper, 1990). Myotonic Muscular
Dystrophy, also known as dystrophia myotonica or myotonia
atrophica, is characterized by progressive muscle wasting
and weakness combined with myotonia. It is one of the most
common forms of inherited muscle disease. Unlike other forms
of muscular dystrophy, the difficulties that most individuals
with MMD have do not set in until adolescence or adulthood.
Thus many people with this form of muscular dystrophy can
be mobile and relatively independent throughout their lives.
The exception to this is congenital
myotonic muscular dystrophy, which can cause symptoms
at birth. Almost all affected individuals have some level
of myotonia and muscle weakness due to atrophy or shrinkage
of the muscles.
Myotonic Dystrophy
Autosomal Dominant Diagram
Inheritance Diagram
Clinical Picture
The weakening and wasting of muscles is characteristic and mainly
includes the facial muscles, sternomastoids, and distal limb
muscles (P.S. Harper, 1990). This pattern is in contrast to
what is seen in most other forms of muscular dystrophy and more
closely resembles myastenia gravis. The myotonia and weakness
tend to gradually worsen over several years. The muscles of
the face are often the first to show weakness, resulting gin
lack of facial expression or a mask-like appearance that has
been labeled with the phrase “myotonic faces.” People
with MMD can have dysarthia. Smooth muscle, particularly of
the gastrointestinal tract is prominently involved. Cardiac
involvement can be severe and may result in sudden death. Patients
may experience arrhythmias, atrial flutter, conduction defects,
possibly due to widespread degeneration of the conducting tissue
at a time when the myocardium as a whole is relatively normal
(P.S. Harper, 1990). Respiratory problems may be present and
are partly due to aspiration and diaphragmatic involvement.
Alveolar hypoventilation, often associated with hypersomnia
is well documented. Post-anesthetic respiratory depression is
also a serious possibility (P.S. Harper, 1990). Ocular abnormalities,
such as cataracts, ptosis, and retinal degeneration can occur,
as can endocrine abnormalities, particularly testicular atrophy
and glucose intolerance.
Associated symptoms
The range of symptoms associated with MMD is classified into
three main types of MMD. However, MMD is very heterogeneous
between individuals and within a family.
The mild type is characterized by mild myotonia,
cataracts, balding, and the potential for diabetes. The
age of onset is generally in adulthood, and these individuals
have a normal lifespan.
The classical type is characterized by muscle weakness
and wasting, myotonia, cataracts, balding, an irregular
heartbeat, and the potential for diabetes. This type is
usually recognized either in childhood, adolescence, or
adulthood. The lifespan may be slightly shortened. Generally,
the earlier the symptoms present, the more severe the disease
is.
Individuals with the third type, congenital MMD,
have severe disease. Symptoms can include severe weakness,
myotonia, breathing and swallowing difficulties, and often
mild to moderate mental retardation. The onset is generally
birth to childhood and their lifespan is shortened. In this
type, the myotonia is not as much a part of the clinical
picture as is the muscle weakness.
Currently there is no medication or cure available for MMD.
Treatment is limited to managing symptoms and minimizing disability
as much as possible. In the case of congenital MMD, early
intervention is extremely important. Hearing and vision abnormalities
should be investigated and diagnosed as soon as possible so
that treatment can be provided. Surgery for uncoordinated
eye muscles and special education can greatly influence a
child’s later success in life.
What causes Myotonic Dystrophy
Almost always, a child born with this type of MMD has a mother
with adult-onset MMD, even though her symptoms may be so mild
that she was never diagnosed officially with the condition.
Mothers with MMD can also pass on the adult-onset form. When
fathers with MMD have children, the child can inherit the disease,
but it is almost always the adult-onset form. This is a genetic
feature seen only with this type of muscular dystrophy.
The genetic change that causes MMD is a trinucleotide repeat
(CTG). In general, the bigger the expansion, the earlier the
onset of symptoms. Anticipation cannot be predicted and doesn’t
always occur, however, it has been observed in MMD.
CTG Repeat Size:
Normal Repeat Length: 5-37 repeats
Premutation: 38-49 repeats
Mild MMD: 50-150 repeats
Classical MMD: 100-1000 or 1500 repeats
Congenital MMD: 1000 or more repeats
There is another type of MMD called Myotonic Dystrophy
Type 2. Less is known about this type of MMD. We do know
that individuals with type 2 will have proximal myotonic muscle
disease, with other symptoms similar to type I MMD. MMD type
2 is also autosomal dominant. The exact gene is not identified
yet, but we know that the location of the gene is found on
Chromosome 3.
Ways a person gets MMD
Autosomal dominant forms
Sporadic Mutations
Diagnosing Myotonic Dystrophy
Take a detailed patient and family history (3 generation
pedigree)
Determine the source of the muscle weakness (nerve or
muscle)
Detailed exam to look for certain signs of MMD: characteristic
long face with hollow temples, early balding in males, abdominal
pain or constipation, cataracts, and trouble with relaxing
ones grip, especially in cold weather
Schedule a muscle biopsy
Genetic testing
Genetic Testing
There is genetic testing available for MMD, which takes on average
2 – 6 weeks for results. It is always most informative
to test an affected individual first for a genetic alteration,
and then proceed to test family members as necessary. It is
important to note that the repeat size cannot be used to predict
the age when a person will develop symptoms or the degree of
symptom progression. We do know that the largest repeat size
is seen in congenital MMD. There is also prenatal genetic testing
available. Before your patient considers genetic testing for
research purposes or for diagnostic testing, it is pertinent
to realize that the decision to be genetically tested is a very
important and personal decision. Genetic counselors are available
to speak with patients about different aspects of inheritance
and genetic testing.
Support
After your patient is diagnosed with MMD, he or she is likely
to feel overwhelmed. It may be helpful to let your patient know
that support is available. Contact your local Muscular Dystrophy
Association Clinic for more information, or visit the web site
at www.mdausa.org.
Additionally, visit the Links section
on this Web site to learn more about other support and information.
Reference:
P.S. Harper. Myotonic dystrophy and related disorders. Principles
and Practice of Medical Genetics. Eds. Emery and Rimoin,
1990.
