Myotonia refers to delayed relaxation after muscle contraction, which can cause muscle stiffness. Muscular dystrophies are inherited, progressive muscle disorders resulting from defects in one or more genes needed for normal muscle structure and function; dystrophic changes (eg, muscle fiber necrosis and regeneration) are seen on biopsy specimens.
Myotonic dystrophy affects about 10 cases per 100,000 in the general population (1 General references Myotonic dystrophy is an autosomal dominant muscle disorder and is among the most common forms of adult-onset muscular dystrophy. Two types are recognized. Both affect voluntary muscles, and... read more ). Inheritance is autosomal dominant Autosomal Dominant Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. If expression of a trait requires only one copy of a gene (one allele)... read more with variable penetrance. Two types are recognized, with different genetic loci. Type 1 DM (DM1) involves expansion of a CTG trinucleotide repeat of the DMPK gene located on chromosome 19. Type 2 DM (DM2) is milder and involves a CCTG repeat expansion mutation of the cellular nucleic acid binding protein gene CNBP (previously known as ZFN9) on chromosome 3q21.3.
Both types affect voluntary muscles, and DM1 also affects involuntary muscles (eg, of the gastrointestinal tract, uterus).
Congenital myotonic dystrophy
Occasionally, myotonic dystrophy is present at birth in children of mothers and, rarely, fathers with DM1 mutations. Offspring may have a severe form of myotonia referred to as congenital myotonic dystrophy. This form is characterized by severe hypotonia (floppy infant), feeding and respiratory difficulties, skeletal deformities, facial weakness, and delayed psychomotor development.
Up to 40% of infants do not survive, usually because of respiratory failure and perhaps cardiomyopathy Overview of Cardiomyopathies A cardiomyopathy is a primary disorder of the heart muscle. It is distinct from structural cardiac disorders such as coronary artery disease, valvular disorders, and congenital heart disorders... read more . Up to 60% of survivors have intellectual disability Intellectual Disability Intellectual disability is characterized by significantly subaverage intellectual functioning (often expressed as an intelligence quotient < 70 to 75) combined with limitations of adaptive... read more (2 General references Myotonic dystrophy is an autosomal dominant muscle disorder and is among the most common forms of adult-onset muscular dystrophy. Two types are recognized. Both affect voluntary muscles, and... read more ).
Congenital myotonic dystrophy should not be confused with myotonia congenita Myotonia Congenita Myotonia congenita is an inherited disorder causing muscle stiffness and hypertrophy beginning during childhood. There are 2 main types with different modes of inheritance and manifestations... read more , a separate disorder.
1. Liao Q, Zhang Y, He J, Huang K: Global Prevalence of Myotonic Dystrophy: An Updated Systematic Review and Meta-Analysis. Neuroepidemiology 56(3):163-173, 2022. doi: 10.1159/000524734
2. Darras BT, Volpe JJ: Muscle involvement and restricted disorders. In Volpe's Neurology of the Newborn, ed. 6, edited by Volpe JJ, Inder TE, Darras BT, et al. Elsevier, Philadephia, 2018, p. 922.
Symptoms and Signs of Myotonic Dystrophy
Symptoms and signs of myotonic dystrophy begin during adolescence or young adulthood and include myotonia (delayed relaxation after muscle contraction, which may be asymptomatic or described as muscle stiffness), weakness and wasting of distal limb muscles (especially in the hand and foot, leading sometimes to footdrop) and facial muscles (ptosis is especially common), and cardiomyopathy. Intellectual disability, cataracts, and endocrine disorders can also occur. Men may have small testes. Both men and women may have premature frontal balding.
Because of involuntary muscle involvement, patients with DM1 may also have dysphagia and constipation; uterine muscle abnormalities may cause problems for women during labor and delivery.
Diagnosis of Myotonic Dystrophy
DNA mutation analysis
Diagnosis of myotonic dystrophy is indicated by characteristic clinical findings, age at onset, and family history and is confirmed by DNA testing.
Treatment of Myotonic Dystrophy
Myotonia may respond to membrane-stabilizing medications (eg, mexiletine, lamotrigine, carbamazepine, phenytoin). Of these, mexiletine has been shown to significantly reduce myotonia in nondystrophic myotonia and is thus the first-line medication for patients with myotonic dystrophy who have functionally limiting myotonia (1 Treatment references Myotonic dystrophy is an autosomal dominant muscle disorder and is among the most common forms of adult-onset muscular dystrophy. Two types are recognized. Both affect voluntary muscles, and... read more , 2 Treatment references Myotonic dystrophy is an autosomal dominant muscle disorder and is among the most common forms of adult-onset muscular dystrophy. Two types are recognized. Both affect voluntary muscles, and... read more ). Because mexiletine can rarely precipitate arrhythmias in patients with underlying ventricular arrhythmias, it is contraindicated in patients with second- or third-degree atrioventricular block; consultation with a cardiologist is recommended before initiating mexiletine therapy, particularly in those with an abnormal ECG.
However, it is weakness, for which no treatment is available, and not myotonia, that usually disables the patient; braces for footdrop are usually required as the disease progresses.
1. Logigian EL, Martens WB, Moxley RT 4th, et al: Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type 1. Neurology 74(18):1441-1448, 2010. doi: 10.1212/WNL.0b013e3181dc1a3a
2. Heatwole C, Luebbe E, Rosero S, et al: Mexiletine in Myotonic Dystrophy Type 1: A Randomized, Double-Blind, Placebo-Controlled Trial. Neurology 96(2):e228-e240, 2021. doi: 10.1212/WNL.0000000000011002
Prognosis for Myotonic Dystrophy
Death is most commonly due to respiratory and cardiac disease, and patients who develop cardiac arrhythmias Overview of Arrhythmias The normal heart beats in a regular, coordinated way because electrical impulses generated and spread by myocytes with unique electrical properties trigger a sequence of organized myocardial... read more and severe muscle weakness at a younger age are at increased risk of premature death. Mean age at death is 55 years (1 Prognosis reference Myotonic dystrophy is an autosomal dominant muscle disorder and is among the most common forms of adult-onset muscular dystrophy. Two types are recognized. Both affect voluntary muscles, and... read more ).
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