Download Myotonic distrophy type1 What is myotonic dystrophy?

What is myotonic dystrophy?
Myotonic dystrophy is part of a group of inherited disorders
called muscular dystrophies. It is the most common form of
muscular dystrophy that begins in adulthood.
 Myotonic dystrophy is characterized by progressive muscle
wasting and weakness. People with this disorder often have
prolonged muscle contractions (myotonia) and are not able to
relax certain muscles after use. For example, a person may have
difficulty releasing their grip on a doorknob or handle. Also,
affected people may have slurred speech or temporary locking
of their jaw.
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signs and symptoms of myotonic
dystrophy
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Other signs and symptoms of myotonic dystrophy
include clouding of the lens of the eye (cataracts) and
abnormalities of the electrical signals that control the
heartbeat (cardiac conduction defects). In affected men,
hormonal changes may lead to early balding and an
inability to father a child (infertility). The features of this
disorder often develop during a person's twenties or
thirties, although they can occur at any age. The severity
of the condition varies widely among affected people,
even among members of the same family.
What genes are related to
myotonic dystrophy?
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Myotonic dystrophy is a genetic condition which is inherited in an
autosomal dominant pattern and thus will be passed along to 50% of a
carrier's offspring, on average.
Myotonic dystrophy is one of several known trinucleotide repeat
disorders. Certain areas of DNA have repeated sequences of two or three
nucleotides.
DM1
In DM1, the affected gene is called DMPK, which codes for myotonic
dystrophy protein kinase, a protein expressed predominantly in skeletal
muscle. The gene is located on the long arm of chromosome 19.
In DM1, there is an expansion of the cytosine-thymine-guanine
(CTG) triplet repeat in the DMPK gene. Between 5 and 37 repeats
is considered normal, while individuals with between 38 and 49
repeats are considered to have a pre-mutation and are at risk of
having children with further expanded repeats and, therefore,
symptomatic disease.Individuals with greater than 50 repeats are
almost invariably symptomatic, with some noted exceptions.[ref]
Longer repeats are usually associated with earlier onset and more
severe disease.
 DMPK alleles with greater than 37 repeats are unstable and
additional trinucleotide repeats may be inserted during cell
division in mitosis and meiosis. Consequently, the children of
individuals with premutations or mutations inherit DMPK alleles
which are longer than their parents and therefore are more likely
to be affected or display an earlier onset and greater severity of
the condition, a phenomenon known as anticipation.
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Myotonic dystrophy subtypes
Type
Gene
Repeat
Anticipati
on
Severity
DM1
DMPK
CTG
Yes
Moderate
-severe
DM2
ZNF9
CCTG
Minimal/n
one
Mildmoderate
Clinical Diagnosis
Myotonic dystrophy type 1 (DM1) is suspected in adults
with the following:
 Muscle weakness, especially of the distal leg, hand, neck,
and face
 Myotonia (sustained muscle contraction), which often
manifests as the inability to quickly release a hand grip (grip
myotonia) and which can be demonstrated by tapping a
muscle (e.g., the thenar muscles) with a reflex hammer
(percussion myotonia)
 Posterior subcapsular cataracts detectable as red and green
iridescent opacities on slit lamp examination
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DM1 is suspected in neonates with some
combination of the following:
Hypotonia
Facial muscle weakness
Generalized weakness
Positional malformations including club foot
Respiratory insufficiency
Testing
Electromyography (EMG).
Serum CK concentration..
Muscle biopsy.
Management
There is currently no cure for or treatment specific to myotonic
dystrophy. Therefore, the focus is on managing the complications
of the disease, particularly those relating to the cardiopulmonary
system as these account for 70% of deaths due to DM1. Pacemaker
insertion may be required for individuals with cardiac conduction
abnormalities. Central sleep apnoea or obstructive sleep apnoea
may cause excessive daytime sleepiness, and these individuals
should undergo a sleep study. Otherwise, there is evidence for the
use of modafinil as a central nervous system stimulant.
 Some small studies have suggested that imipramine, clomipramine
and taurine may be useful in the treatment of myotonia. However,
due to the weak evidence and potential side effects such as cardiac
arrhythmias, these treatments are rarely used.
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Treatment
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Currently, researchers are looking for a treatment on the
molecular level, a molecule capable of releasing and enabling
trapped proteins. It has shown promise, but it still in its
infancy. In the meantime, medical professionals are left to
treat and mask the symptoms. Many doctors must be
involved in this effort: • Primary care physicians •
Gastrointestinal specialists • Eye surgeons • Ear nose and
throat surgeons • Orthopedic surgeons, neurologists • Pain
management doctors Under normal circumstances, each of
these doctors should be visited at least once, if not twice, a
year. In addition, Type 1 patients whose condition is
progressing rapidly (which usually begins to happen about ten
years after the onset of symptoms) should have both an EKG
and ECG done every three months.
By Faeze heidari
medical91