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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