Autosomal recessive myotonia congenita is a nondystrophic skeletal muscle disorder characterized by muscle stiffness and an inability of the muscle to relax after voluntary contraction. Most patients have symptom onset in the legs, which later progresses to the ... Autosomal recessive myotonia congenita is a nondystrophic skeletal muscle disorder characterized by muscle stiffness and an inability of the muscle to relax after voluntary contraction. Most patients have symptom onset in the legs, which later progresses to the arms, neck, and facial muscles. Many patients show marked hypertrophy of the lower limb muscles. Some patients show transient muscle weakness (Koch et al., 1993). Becker disease is more common and more severe than Thomsen disease.
Te Kamp (1907) reported possible homozygosity in cases of myotonia congenita.
Becker (1966) concluded that a recessive form of myotonia congenita is more frequent and more severe than the dominant myotonia congenita of Thomsen. Segregation ratios ... Te Kamp (1907) reported possible homozygosity in cases of myotonia congenita. Becker (1966) concluded that a recessive form of myotonia congenita is more frequent and more severe than the dominant myotonia congenita of Thomsen. Segregation ratios and the frequency of parental consanguinity suggested recessive inheritance. Winters and McLaughlin (1970) described myotonia congenita in 2 brothers and a sister with normal parents. Harper and Johnston (1972) reported a particularly interesting family in which 3 children of first-cousin parents were affected. Becker (1977) reviewed the features distinguishing recessive from dominant myotonia. Although called myotonia congenita, the recessive form is not manifest at birth; it manifests between 4 and 12 years and, especially in males, as late as 18 years. It is a progressive disorder, starting in the legs and in a few years affecting the arms and finally the masticatory and facial muscles. Heiman-Patterson et al. (1988) described 2 sisters with myotonia congenita who, on halothane contracture testing of skeletal muscle in vitro, had findings consistent with susceptibility to malignant hyperthermia (145600). The proposita was a 31-year-old woman who developed generalized muscle stiffness on exposure to succinylcholine. Intubation was difficult and she had generalized muscle stiffness, including opisthotonos and decerebrate posturing. Lifelong clumsiness and rare cramping were the only neuromuscular complaints, and there was no clinical myotonia. A 42-year-old sister had a positive contracture test and, by history, muscle stiffness since early childhood that increased with exercise and involved her hands and eyelids. During 2 surgical procedures, she developed muscle rigidity without rise in temperature on exposure to succinylcholine. Neurologic examination showed lid lag and myotonia in all muscles tested. In both patients, slit-lamp was negative for the changes of myotonic dystrophy, and the EKG was normal. No information was provided on the parents. Dupre et al. (2009) reported 27 French Canadian patients with autosomal recessive myotonia associated with biallelic CLCN1 mutations (see, e.g., 118425.0009; 118425.0015; 118425.0019). The mean age at onset was 10 years (range, 3 to 34). Clinical features included lid lag (26%), lid myotonia (37%), tongue myotonia (63%), percussion myotonia (96%), handgrip myotonia (89%), transient weakness (48%), warm-up phenomenon (100%), generalized hypertrophy (55%), generalized stiffness (93%), muscle pain (41%), exacerbation with cold temperatures (63%) and a hormonal effect in women (46%). This latter subset of woman reported aggravation of symptoms during menstrual periods, aggravation during pregnancy, or alleviation after menopause. In addition, some patients reported that alcohol alleviated symptoms. Many patients took medication for symptom alleviation. Although some were resistant, the most effective medications were phenytoin and gabapentin. Electrophysiologic studies showed more severe myotonia and larger CMAP decrements on repetitive nerve stimulation compared to patients with dominant myotonia due to heterozygous CLCN1 mutations. Dupre et al. (2009) noted that the short exercise test is less painful, but just as accurate as repetitive nerve stimulation in assessing CMAP decrements.
In 3 brothers, born of consanguineous parents, with autosomal recessive myotonia congenita, Koch et al. (1992) identified a homozygous mutation in the CLCN1 gene (118425.0001).
In affected members of a German family with recessive myotonia, Lorenz ... In 3 brothers, born of consanguineous parents, with autosomal recessive myotonia congenita, Koch et al. (1992) identified a homozygous mutation in the CLCN1 gene (118425.0001). In affected members of a German family with recessive myotonia, Lorenz et al. (1994) identified compound heterozygosity for 2 mutations in the CLCN1 gene (118425.0003; 118425.0004). In affected members of 18 unrelated families from Norway and Sweden with both autosomal dominant (5 families) and autosomal recessive (13 families) inheritance of myotonia congenita, Sun et al. (2001) identified 8 different mutations in the CLCN1 gene. Fifteen patients had mutations on both alleles, consistent with the recessive disorder; 2 probands had mutations in a single allele; and 2 probands had no CLCN1 mutations. In 2 families, 3 CLCN1 mutations were found in the proband, and Sun et al. (2001) suspected that this phenomenon may be underestimated because mutation search in a disease gene usually ends by the identification of 2 mutations in a family with recessive inheritance. Families with apparently dominant segregation of myotonia congenita may actually represent recessive inheritance with undetected heterozygous individuals married-in as a consequence of a high population carrier frequency of some mutations. The findings, together with the very variable clinical presentation, challenged the classification into dominant Thomsen or recessive Becker disease. Sun et al. (2001) suggested that most cases of myotonia congenita show recessive inheritance with some modifying factors or genetic heterogeneity. Raja Rayan et al. (2012) performed multiplex ligation-dependent probe amplification (MLPA) specific to the CLCN1 gene in 60 families with recessive myotonia congenita in whom either no mutations or only a single pathogenic CLCN1 mutation had been identified. The results were positive in 4 (6.7%) patients: 2 unrelated patients were found to have 2 different multiexon deletions within the CLCN1 gene on the second allele, and 2 additional patients had a homozygous duplication of exons 8 through 14 of the CLCN1 gene (118425.0020). The 2 patients with the duplication were both of Iraqi origin, but were unrelated. Both Iraqi patients had a severe form of the disorder with onset in infancy. Haplotype analysis suggested a founder effect for this duplication mutation. Raja Rayan et al. (2012) concluded that copy number variation involving the CLCN1 gene is an important genetic mechanism in patients with recessive myotonia congenita, and that MLPA analysis may aid in genetic counseling.
Sun et al. (2001) stated that the worldwide prevalence of myotonic congenita, both dominant and recessive forms, is 1:100,000. In the northern Norwegian population, Sun et al. (2001) found a prevalence of about 9:100,000, which was comparable to ... Sun et al. (2001) stated that the worldwide prevalence of myotonic congenita, both dominant and recessive forms, is 1:100,000. In the northern Norwegian population, Sun et al. (2001) found a prevalence of about 9:100,000, which was comparable to the Finnish experience.
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