1/326. myotonic dystrophy associated with QT prolongation and torsade de pointes. A rare case of myotonic dystrophy (MD) with congestive heart failure, associated with QT prolongation and torsade de pointes (TdP) is reported. A 53-year-old woman was admitted to the hospital because of congestive heart failure. Electrocardiograph (ECG) showed first-degree atrioventricular block and QT prolongation. During hospitalization, TdP appeared but returned to sinus rhythm spontaneously. As the patient had quadriplegia, a myopathic face, cataracts, diabetes mellitus, and an increased number of cytosine-thymineguanine (CTG) repeats (760 repeats), she was diagnosed as having MD. Electrocardiographic analysis of her family also revealed abnormal QT(U) prolongation in her daughter and brother who both had MD, while ECG findings of other family members without MD were normal. Thus, the presence of QT(U) prolongation was associated with MD in this family. ( info) |
2/326. Expansion of CTG repeat in myotonin protein kinase gene on Alu(ins)-HinfI-I background in a myotonic dystrophy patient from india. Mutations in brief no. 210. Online. To determine the founder of Indian myotonic dystrophy mutation, we have studied the expansion of CTG repeats in myotonin protein kinase gene and two intragenic linked loci Alu(ins) / Alu(del) and G/T intron 9 HinfI polymorphism in ten unrelated DM patients from eastern india. Out of these ten patients, reconstruction of haplotype was possible for five patients unambiguously. In the other five cases, haplotype for the normal allele was assumed to be the most common haplotype found in normal individuals from Indian populations. Such analysis showed that in nine cases, the expansion of CTG repeats took place on Alu(ins)-HinfI-2 background indicating common founder with other DM mutation published. However, in one case we observed a different haplotype [Alu(ins)-HinfI-1] which could be a new mutation or due to admixture. ( info) |
| An autopsy case of myotonic dystrophy (MD) is reported. The patient was a 58-year-old male. He presented with muscular weakness and muscular atrophy at the age of 33 and was diagnosed as having MD from myotonic symptoms (i.e. percussion and grip myotonia) at 49 years old. mental disorders including a delusional hallucinatory state, mental slowness, indifference, and lack of spontaneity as well as visual cognitive impairments were noted at the age of 55. He showed Parkinsonism and died of septic shock. T2-weighted magnetic resonance imaging demonstrated diffuse cortical atrophy with a marked frontal atrophy and high-intensity signals in the white matter. Single photon emission computed tomography demonstrated hypoperfusion in the frontal cortex. Neuropathologic observation revealed neuronal loss in the superficial layer of the frontal and parietal cortices and extensive neuronal loss in the occipital cortex, intracytoplasmic inclusion body in the nerve cell of the medial thalamic nuclei, neuronal loss and presence of lewy bodies in the substantia nigra and locus ceruleus corresponding to the pathologic features of Parkinson's disease, as well as abnormalities of myelin in the white matter. The present case suggests that in MD brain, various neuropathologic changes may occur and they contribute to the mental disorders. ( info) |
4/326. myotonic dystrophy and progressive cognitive decline: a common condition or two separate problems? We report the case of NG, a 43-year old woman with myotonic dystrophy (MYD) who has shown a slow decline in both motor and cognitive abilities since her referral to us at age 32. MYD is an autosomal dominant disorder characterised by weakening and wasting of the muscles together with impaired muscle relaxation. Cognitive abilities are usually little affected in the adult onset form, although there is a high risk of cognitive impairment in those with childhood onset. Cognitive decline is also typically associated with maternal inheritance. NG, who was diagnosed with MYD at the age of 18, inherited it from her father. We report the decline in NG's cognitive abilities over 11 years of longitudinal assessment, and consider whether she is an atypical MYD patient or whether the MYD and cognitive decline are attributable to two separate pathological processes. ( info) |
| We present the clinical and neuroimaging findings of five patients (four males, one female; mean age 12 years) affected by congenital myotonic dystrophy and the correlation with their molecular genetic analysis. At birth all five presented severe muscular weakness and hypotonia, associated with feeding difficulties and respiratory distress. In the same patients, congenital clubfoot or more generalized arthrogryposis was also evident. Lymphocyte dna was characterized in each by a CTG repeat longer than 1300 in the region of the myotonic dystrophy gene in chromosome 19. The patients' neurological condition was evaluated by clinical examination, intelligence tests, electroencephalography, and brain magnetic resonance imaging. All five suffered from some impairment of intellectual function (IQ ranged from 52 to 79). In three a longitudinal evaluation of the cognitive deficit detected no deterioration. In all patients magnetic resonance imaging showed some degree of ventricular dilatation, loosely correlated to the cognitive impairment; in three there was hypoplasia of the corpus callosum and in two mild abnormalities of supratentorial white matter. The relationship between the size of the CTG repeat expansion found in lymphocyte dna and the cerebral abnormalities appeared inconsistent in this unusual myoencephalopathy of the newborn. ( info) |
6/326. Pharyngeal flap for velopharyngeal incompetence in patients with myotonic dystrophy. Velopharyngeal incompetence (VPI) has been associated with neuromuscular disorders. Only 4 patients with myotonic dystrophy (MD) who underwent pharyngeal flap elevation for VPI have been reported in the literature. In 3 patients, surgery preceded the diagnosis of MD. Cardiorespiratory complications characterized the postoperative period of 3 patients. The authors present 3 patients with VPI and an established diagnosis of MD (by molecular genetics) who underwent pharyngeal flap elevation. The operation resulted in a major improvement in speech in all patients, although some relapse was noted later in 1 patient. Contrary to previous reports, none had peri- or postoperative cardiorespiratory complications. MD, although an uncommon etiology, should be considered in cases of late-onset VPI. Owing to differences between the authors' findings and previous reports, additional studies are needed before final conclusions can be reached regarding the benefit and safety of pharyngeal flap surgery in MD patients. At present, MD should not be considered a contraindication for this procedure, although close perioperative monitoring is indicated. ( info) |
| The fulminant forms of congenital myotonic dystrophy, which rapidly lead to death, are difficult to diagnose. The case described illustrates the roles of persistent pulmonary hypertension in such a fatal form. ( info) |
8/326. Proximal myotonic myopathy (PROMM) presenting as myotonia during pregnancy. Proximal myotonic myopathy is a recently described autosomal dominant condition characterized by proximal myopathy, cataracts, intermittent myotonia, and myalgia. We report a further family with this condition. The proband and her two sisters presented with myotonia during pregnancy which resolved after each delivery. Two sisters experienced myalgia between each pregnancy. This relationship between pregnancy and symptom exacerbation suggests an intriguing hormonal influence in PROMM. ( info) |
9/326. Antenatal and preoperative genetic and clinical assessment in myotonic dystrophy. The antenatal investigation of an obstetric patient with a history of myotonia is described. The smooth and striated muscle dysfunction in myotonic dystrophy renders these patients, as a group, liable to surgical correction and exposure to anaesthesia. A caesarean section is reported to illustrate the preferred timing of diagnosis and peripartum management. While regional anaesthesia is preferred, myotonic dystrophy is not a contraindication to general anaesthesia, provided risks are anticipated and steps taken to minimize complications. ( info) |
10/326. Reduction of the DM-associated homeo domain protein (DMAHP) mRNA in different brain areas of myotonic dystrophy patients. myotonic dystrophy (DM) is a multisystemic disease caused by expansion of a CTG trinucleotide repeat in the 3' untranslated region of the DMPK protein kinase gene on chromosome 19q13.3. The mechanism by which this expansion causes disease remains unknown. It has been suggested that CTG expansion not only affects the expression of the DMPK gene, but also alters the nuclear rna metabolism and expression of neighboring genes. DMAHP, which is expressed in various human tissues, including skeletal muscle, heart and brain, is immediately distal to the 3' end of DMPK gene, in a CpG island which contains the CTG repeat. Here we report a 4- to 5-fold reduction of the expression of the DMAHP gene in different brain areas of DM patients. Our results demonstrate that [CTG]n expansion alters the brain DMAHP mRNA expression supporting a dominant-negative effect at the cellular level of DM [CTG]n mutation. The reduced brain expression of DMAHP could explain cerebral impairment in DM patients. ( info) |