Disease relevance of Myotonic Disorders

• A patient with paramyotonia congenita, a related disorder with myotonia and episodic weakness, was studied during treatment with acetazolamide [1].
• We have applied these polymorphisms to the investigation of hyperkalemic periodic paralysis and paramyotonia congenita, distinct neuromuscular disorders both of which are thought to involve mutation at SCN4A [2].
• Structural and functional mutations of the perlecan gene cause Schwartz-Jampel syndrome, with myotonic myopathy and chondrodysplasia [3].
• BACKGROUND: Previous investigations in three families have shown that proximal myotonic myopathy (PROMM) is not linked to the gene loci for myotonic dystrophy (DM) or to the loci of the genes of the muscle sodium and chloride channels associated with other myotonic disorders [4].

Psychiatry related information on Myotonic Disorders

• Here, we describe the phenotype and the histological features in muscle and brain of the first large pedigree with a non-myotonic dystrophy type 1 (DM1) non-DM2 multisystem myotonic disorder associated with severe frontotemporal dementia [5].

High impact information on Myotonic Disorders

• Two paramyotonia congenita mutations, R1448H and R1448C, substitute histidine and cysteine for arginine in the S4 segment of domain 4 [6].
• Acetazolamide-induced weakness in paramyotonia congenita [1].
• Dinucleotide repeat polymorphisms at the SCN4A locus suggest allelic heterogeneity of hyperkalemic periodic paralysis and paramyotonia congenita [2].
• Different effectiveness of tocainide and hydrochlorothiazide in paramyotonia congenita with hyperkalemic episodic paralysis [7].
• BACKGROUND: Myotonic dystrophy type 2/proximal myotonic myopathy (DM2/PROMM) is an autosomal dominant multisystem disorder [8].

Chemical compound and disease context of Myotonic Disorders

• Characterization of a new sodium channel mutation at arginine 1448 associated with moderate Paramyotonia congenita in humans [9].
• Successuful treatment of paramyotonia congenita (Eulenburg): muscle stiffness and weakness prevented by tocainide [10].
• The enhanced use-dependent block as seen with R1448H may explain the extraordinary therapeutic efficacy of mexiletine in most patients with paramyotonia congenita [11].
• The anesthetic propofol modulates gating in paramyotonia congenita mutant muscle sodium channels [12].
• To investigate the pathomechanism of paramyotonic stiffness, the mechanogram of isometric finger force and the electromyogram of the flexor digitorum muscle were simultaneously recorded in five unrelated paramyotonia congenita patients [13].

Biological context of Myotonic Disorders

• Hyperkalaemic periodic paralysis, paramyotonia congenita and a small heterogeneous group of related 'pure' myotonias are autosomal dominant disorders and are due to at least 16 different mutations in the SCN4A (SkM1) adult skeletal muscle sodium channel gene on chromosome 17q23-25 [14].
• The autosomal dominantly inherited phenotype of paramyotonia congenita (PC) without paralysis on exposure to cold MIM 168350) was originally described by De Jong in 1955 [15].
• Measures of heart rate variability tended to be lower in myotonic dystrophy type 2/proximal myotonic myopathy patients compared to healthy controls, but reached statistical significance only for the number of R-R intervals exceeding 50 ms (p50) and the power spectrum density in the low-frequency range (low-frequency power) [16].
• Still other diseases associated with abnormal energy metabolism include lipid-related disorders (carnitine and carnitine palmitoyl-transferase deficiencies) and myotonic syndromes (myotonia congenita, paramyotonia congenita, hypokalemic and hyperkalemic periodic paralysis, and malignant hyperexia) [17].

Gene context of Myotonic Disorders

• More recently a second form of multisystem myotonic disorder has been recognized and variously designated as proximal myotonic myopathy (PROMM), proximal myotonic dystrophy (PDM), or DM2 [18].
• Dominantly inherited proximal myotonic myopathy and leukoencephalopathy in a family with an incidental CLCN1 mutation [19].
• Hyperparathyroidism in a patient with proximal myotonic myopathy (PROMM) [20].
• Careful clinical evaluation of patients with DM2/PROMM shows that the similarities among the multisystemic myotonic disorders outweigh the differences [21].
• We have also excluded the MN1 disease locus from the chromosomal regions containing the genes for the muscle sodium (alpha- and beta-subunits) and chloride channels, both of which are involved in other myotonic disorders [22].

Analytical, diagnostic and therapeutic context of Myotonic Disorders

• Genetic analysis of the adult muscle sodium channel alpha-subunit, SCN4A gene on chromosome 17q, was performed by means of PCR technique in a Swedish family with paramyotonia congenita (Eulenburg) (PMC) [23].

References