Organ Dysfunction and Muscular Disability in Myotonic Dystrophy Type 1

Abstract

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder characterized by muscle weakness and multiple organ impairment, especially the eyes, lung, and heart. We conducted the current study to analyze the prevalence and intercorrelation among these disorders and their respective relationships with muscular disability. We assessed medical history, anthropometric data, lung volumes, arterial and venous blood samples, surface 12-lead electrocardiogram, echocardiography, ophthalmologic examination, and muscular impairment rating scale (MIRS) in 106 patients (48 male and 58 female) with DM1, aged 43.7 ± 12.8 years. Obesity, hypertriglyceridemia, and diabetes were found in respectively 25.6%, 47.6%, and 17.1% of patients. Disabling cataract was found in 43.4%, and was independently predicted by age and MIRS. Restrictive lung disease was noted in 34%, and was predicted by MIRS, CTG repeat expansion, and body mass index. Conduction disorders were found in 30.2% of patients and were predicted by left ventricular ejection fraction, MIRS, and CTG repeat expansion.We found significant relationships between cataract, restrictive lung disease, and conduction disorders: patients with cataract and those with conduction disorders exhibited more severe restrictive lung disease than the other patients. Conversely, the relative risk of restrictive lung disease was 2.42 (1% confidence interval [CI], 1.06-5.51) in patients with cataract and 2.54 (1% CI, 1.26-5.07) in patients with conduction disorders. Multivariate analysis revealed that MIRS was the only independent predictor for conduction disorders and restrictive lung disease. MIRS ≥3 and MIRS ≥4 were the best simple cutoff values to predict, respectively, lung and cardiac involvements.To conclude, muscular disability, ophthalmologic, and cardiac and pulmonary involvement are strongly correlated. Particular attention should be given to these entities in patients with distal or proximal muscular weakness.

Lack of correlation between the ventilatory response to CO2 and lung function impairment in myotonic dystrophy patients: Evidence for a dysregulation at central level

“…Besides the classical view as a neuromuscular disease (the majority of DM1 research focused on neuromuscular aspects), nowadays DM1 has to be also considered as a brain disorder regarding the central nervous system (CNS) and cognitive dysfunctions. Indeed, if lung function impairment [5] or cardiac conduction diseases [6,7] have been well described and have a clear prognostic value, the major issues affecting quality of life in DM1 patients are the CNS and cognitive dysfunctions [8,9]. The control of breathing has been shown to be affected, with the description of numerous clinical findings such as irregular breathing pattern [10], sleep breathing disorders [11] or excessive daytime sleepiness [12], supporting a dysregulation at the central level.…”

“…DM1 is an autosomal dominant inherited disorder caused by an unstable trinucleotide (CTG) repeat in the 3' untranslated region of a myotonin kinase gene at chromosome 19q13.3 [2]. The clinical course is clearly progressive from distal weakness to proximal weakness and involves multisystem features [3,4]. Besides the classical view as a neuromuscular disease (the majority of DM1 research focused on neuromuscular aspects), nowadays DM1 has to be also considered as a brain disorder regarding the central nervous system (CNS) and cognitive dysfunctions.…”

Diagnosis of muscle diseases presenting with early respiratory failure

“…The severity and likelihood of developing RF in DM1 correlate well with the severity of the phenotype [48]. Respiratory muscle weakness was demonstrated in onethird of 106 patients in one series, including some with only distal muscle weakness [48].…”

“…Respiratory muscle weakness was demonstrated in onethird of 106 patients in one series, including some with only distal muscle weakness [48]. Uncommonly, DM1 patients develop overt RF whilst still ambulant, as the case for 3 patients (who had dyspnoea at rest) in one series [49].…”

Surgical treatment of obesity in DM1 – a case report and a review of the literature

“…In adults with DM1 there is a high prevalence of overweight (33%) and obesity (21-26%) [9,10]. Weight loss is difficult in DM1 patients.…”