參考網頁
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=160900
1. Gene map locus
---->19q13.2-q13.3
2.Clinical feature in Muscle and Cardiac
---->Muscle
Unlike the other muscular dystrophies, DM initially involves the distal
muscles of the extremities and only later affects the proximal musculature.
In addition, there is early involvement of the muscles of the head and neck.
Involvement of the extraocular muscles produces ptosis, weakness of eyelid
closure, and limitation of extraocular movements. Atrophy of masseters,
sternocleidomastoids, and the temporalis muscle produces a characteristic
haggard appearance. Bosma and Brodie (1969) demonstrated both myotonia and
weakness in patients with swallowing and speech disability. Myotonia, delayed
muscular relaxation following contraction, is most frequently apparent in the
tongue, forearm, and hand. Myotonia is rarely as severe as in myotonia
congenita and tends to be less apparent as weakness progresses.
---->Cardiac Features
Hawley et al. (1983) suggested that the tendency to have heart block or
arrhythmia with myotonic dystrophy is a familial characteristic. The
implication was that there may be 2 forms of myotonic dystrophy. They studied
18 families and found heart block in 4.
In a single large kindred, Tokgozoglu et al. (1995) compared the cardiac
findings in 25 patients with myotonic dystrophy with age-matched normal
family members. They found that the patients were more likely to have
conduction abnormality (52% vs 9%), mitral valve prolapse (32% vs 9%),
and wall motion abnormality (25% vs 0%). Left ventricular ejection fractions
and stroke volume were reduced compared with normals. Using multivariate
analysis, the number of CTG repeats (range, 69 to 1367; normal, less than
38) was the strongest predictor of abnormalities in wall motion and EKG
conduction. Patients with more extensive neurologic findings had a higher
incidence of wall motion and/or EKG conduction abnormalities. The authors also
found that the relation of mitral valve prolapse to the size of the CTG repeat
was of borderline significance.
Cardiac involvement is well described in adults with myotonic dystrophy.
Bu'Lock et al. (1999) undertook detailed cardiac assessment in 12 children
and young adults with congenital myotonic dystrophy using control data from
137 healthy children and young adults. All patients were in sinus rhythm with
a normal P wave axis. Three had first-degree heart block and 4 had a
borderline P-R interval (200 ms). Four others had more complex conduction
abnormalities. Three patients had mitral valve prolapse. Eleven of the 12
patients had abnormalities of 1 or more parameter of left ventricular
diastolic filling. None of these patients were symptomatic. The authors
commented that the prognostic implications of these findings were unclear;
however, they concluded that echocardiographic assessment of left ventricular
diastolic function may be a useful adjunct to electrocardiographic monitoring
of patients with congenital myotonic dystrophy.
Antonini et al. (2000) performed a prospective study of 50 DM1 patients
without known cardiac disease at the time of enrollment. Nineteen patients
developed major cardiac abnormalities during the 56-month study. No
correlation was found between CTG length and frequency of EKG abnormality
or type of arrhythmia. CTG length was inversely correlated with age at onset
of EKG abnormality.
Bassez et al. (2004) reported 11 DM1 patients under the age of 18 years who
had severe cardiac involvement. Two patients died suddenly, 1 patient had
cardiac arrest with successful resuscitation, and 1 asymptomatic 13-year-old
girl presented with recurrent presyncope. Rhythm disturbances included atrial
flutter in 4, ventricular tachycardia in 4, and atrial fibrillation in 1. Five
patients had atrioventricular block necessitating pacemaker implantation. Six
of 11 patients (55%) experienced arrhythmic events with vigorous exercise.
Genetic analysis detected between 235 and 1,200 CTG repeats in all patients.
No cardiac involvement was detected before age 10 years. Bassez et al. (2004)
concluded that patients with congenital or childhood forms of DM1 may present
with cardiac abnormalities and that exercise testing is a necessary evaluation
in these patients.
3.Thw mechanism of molecular genetics for MD disease
---->CTG Triplet Repeat
the diversity of phenotype in myotonic dystrophy may be due to the fact
that the DM CTG repeat induces long-range cis chromosomal effects that
suppress diverse genes on chromosome 19, resulting in manifest multisystem
abnormalities in the clinical disorder.
4.DIAGNOSIS
---->In classic adult-onset cases, clinical diagnosis is straightforward with
demonstration of progressive distal and bulbar dystrophy in the presence of
myotonia, with frontal balding, and cataracts. Confirmatory evidence is
provided by demonstration of depressed IgG and elevated CPK in the serum.
Clinical diagnosis can be difficult in mild cases, where cataracts may be
the only manifestation (Bundey et al., 1970).
Direct analysis of the size of the CTG repeat by Southern blotting permits
DNA diagnosis. Normal individuals have 5 to 37 CTG repeats, whereas patients
have from more than 50 to several thousand CTG repeats in peripheral
leukocytes (see review by Pizzuti et al., 1993).
Reardon et al. (1992) described a 5-year experience in providing
presymptomatic and prenatal molecular diagnostic services based on the
linkage principle using closely linked markers in 161 families. Only 10
analyses out of 235 proved uninformative, but a further 5 requests (1.9%)
could not be reported because of uncertainty in clinical status. Seven of
81 (8.6%) patients considered to be at low risk on clinical grounds were
found to be at high risk of carrying the gene. Reardon et al. (1992)
emphasized that careful clinical examination and appropriate investigations
of nonmolecular nature remain a cornerstone of diagnosis.
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