Neuromuscular disorders
Angus Clarke, Alex Murray, Julian Sampson in Harper's Practical Genetic Counselling, 2019
Other myotonic syndromes are rare in comparison with myotonic dystrophy, which must be carefully excluded (Table 13.5). Myotonia congenita (Thomsen disease) is heterogeneous and at least half the cases are recessively inherited, despite the prominence of some large dominantly inherited families. The two types show clinical as well as genetic differences. Because new mutations for this benign condition are likely to be rare, it is wise to give a one in four risk for further children born to healthy parents of an isolated case, until a molecular diagnosis has been achieved. Correspondingly, the risk of such an isolated case transmitting the condition is, in the absence of a molecular diagnosis, small. Careful neurophysiological tests by an expert are important in distinguishing the different disorders in this group.
The Second Half of the Nineteenth Century
Arturo Castiglioni in A History of Medicine, 2019
In the field of German psychiatry are to be noted such names as that of Karl wernicke (1848-1905), who composed two treatises on diseases of the brain and insanity and also an excellent atlas of the brain. Emil kraepelin (1856-1926), Professor of Psychiatry in various German universities, was one of the pioneers in experimental psychiatry; he introduced one of the simplest classifications of psychopathologic disease, and established the clinical pictures of dementia praecox and manic-depressive insanity. His textbook was published in 1896. The Swiss P. E. bleuler (1857–1939) also brought an important contribution to the study of dementia praecox (schizophrenia) in the second volume of Aschaffenburg’s textbook, 1911. The Dane A. J. T. thomsen (1815-1896), of Schleswig, in 1876 described a new form of disease, myotonia congenita (“Thomsen’s disease”), from which he himself suffered.
Neurogenetics
John W. Scadding, Nicholas A. Losseff in Clinical Neurology, 2011
Myotonia is a disorder in which muscle stiffness occurs as a result of failure of muscle relaxation. Myotonia congenita may be dominant (Thomsen’s disease) or recessive (Becker’s disease). Myotonia may be detected clinically or on electromyography (EMG). Both types are caused by mutations in the muscle chloride channel gene (CLCN1). Paramyotonia congenita is a myotonic autosomal dominant disorder that occurs during exercise and, in contrast to myotonia congenita, worsens with activity. This disorder is caused by mutations in the muscle sodium channel SCN4A, which also causes hyperkalaemic periodic paralysis.
Identification of two novel compound heterozygous CLCN1 mutations associated with autosomal recessive myotonia congenita
Published in Neurological Research, 2019
Zhang Wei, Meng Huaxing, Wang Xiaomei, Wang Juan, Chang Xueli, Zhang Jing, Guo Junhong
Myotonia congenita (MC) is a genetic muscular disease characterized by impaired muscle relaxation after voluntary contraction (myotonia) [1,2]. It is caused by reduced sarcolemmal chloride conductance duo to mutations in the CLCN1 gene coding for the skeletal muscle voltage-gated chloride channel CLC-1 [3,4]. MC may be inherited as either an autosomal dominant (Thomsen disease, OMIM#160,800) or recessive trait (Becker disease, OMIM#255,700), and Becker disease exhibits a generally more severe phenotype[5]. Affected patients complain of muscle stiffness, which appears upon initiating movement following a period of rest and improves with several repetitions of the same movement (warm-up phenomenon) [2,5]. Rapid voluntary movement or mechanical stimulation can also provoke muscle stiffness. Muscular hypertrophy, a finding referred to as an athletic phenotype, is another common sign of MC[2]. Muscle atrophy and transient weakness can be observed in some patients [2,5].
Sodium Channel Myotonia and a Novel Gly701Asp Mutation in the SCN4A Gene: From an Ophthalmological Symptom to a Familial Disease
Published in Neuro-Ophthalmology, 2021
Filipa Sampaio, Sérgia Soares, Sara Pereira, José Alberto Lemos, Ágata Mota
Before the advent of DNA sequencing, non-dystrophic myotonias were differentiated based on clinical phenotypes that had been loosely matched to a specific ion channel. The ones caused by mutations in the CLCN1 gene cause both Thomsen’s (autosomal-dominant) and Becker’s (autosomal-recessive) myotonia congenita. These chloride ion channelopathies present with myotonia associated with muscle hypertrophy and display a characteristic “warm-up phenomenon”.5 The father, grandmother and uncle of the patient in the presented clinical case were initially diagnosed with Thomsen’s myotonia because of the overlapping of the clinical characteristics of the myotonia. The child’s phenotype, in combination with a negative result for a CLCN1 mutation, led to consideration of a sodium channel myotonia diagnosis, which was subsequently confirmed by genetic testing. A previous study screened patients with a clinical diagnosis of Thomsen’s or Becker’s for mutations in both the CLCN1 and SCN4A genes. Approximately 20% of cases were found to have no CLCN1 mutations, and of those all were found to have a SCN4A mutation, showing that sodium channelopathies can mimic the warm-up phenomenon seen with chloride channelopathies.6
Improving genetic diagnostics of skeletal muscle channelopathies
Published in Expert Review of Molecular Diagnostics, 2020
Vinojini Vivekanandam, Roope Männikkö, Emma Matthews, Michael G. Hanna
Myotonia Congenita (MC) is the most common skeletal muscle channelopathy. It is caused by mutations in the CLCN1 gene, which encodes the voltage-gated chloride channel ClC-1. The functional channel protein is comprised of two gene products [5]. The symptoms of myotonia generally present in the first or second decade of life [6]. Symptoms of myotonia are prominent at the initiation of movement and often improve with repeated activity – a phenomenon known as ‘warm up.’ Patients with recessively inherited myotonia congenita tend to have more severe symptoms compared to patients with dominant mutations [5] and additionally, some patients with recessive MC have transient weakness at the initiation of movement. Hundreds of pathogenic mutations have been identified in CLCN1, the majority of CLCN1 mutations are missense, with Gly230Glu the most common [2,7].
Related Knowledge Centers
- Birth Defect
- Channelopathy
- Hypokinesia
- Malignant Hyperthermia
- Muscle Contraction
- Myotonia
- Skeletal Muscle
- Hypertrophy
- Genetic Disorder
- Cramp