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Paramyotonia Congenita

Eulenburg Disease

Paramyotonia congenita is an inherited disorder characterized by progressive muscle stiffness with repeated activities and exposure to cold temperatures. It is an autosomal dominant disorder and results from a defect in the gene that encodes the sodium channel associated with muscle contraction (SCN4A).


Presentation

In persons with paramyotonia congenita, symptoms typically appear early in life, anywhere from infancy to adolescence. Patients complain of an inability to relax muscles and weakening that worsens with repeated activity or prolonged exercise [1]. This is exactly the difference between paramyotonia and classic myotonia in which symptoms are alleviated by physical activity. Symptoms last from minutes to days. The most commonly affected muscles are those in the face and upper extremities [2].

Patients may report worsened symptoms during activities involving cold temperatures such as shoveling snow or while handling frozen foods. Women may experience exacerbation of symptoms during menstruation or pregnancy [3]. Parents may state that their infant's eyes appear to "stick" or the infant has difficulty opening his/her eyes following crying spell [4].

Myopathy
  • Signs of myopathy with central nuclei in the muscle cells were noted in 9 of the patients. 4 of these patients also had small areas with degeneration and, in one, vacuoles were observed.[ncbi.nlm.nih.gov]
  • The myopathy, transmitted by autosomal dominant inheritance, is characterized by a typical past medical history and by the persistent contraction of the muscles of the face, arms and legs provoked by exposure to cold.[ncbi.nlm.nih.gov]
  • […] congenita mutant skeletal muscle sodium channel in vitro, because life-threatening complications resulting from severe muscle rigidity during induction of anesthesia have been observed using other anesthetics in patients with hereditary sodium channel myopathies[ncbi.nlm.nih.gov]
  • Abstract Paramyotonia congenita (OMIM 168300) is a non-dystrophic myopathy caused by mutations in the SCN4A gene that sometimes can be confused with myotonia congenita.[ncbi.nlm.nih.gov]
  • Hanna , Periodic paralysis , Myopathies , 10.1016/S0072-9752(07)86004-0 , (77-106) , (2007) . Frank Lehmann‐Horn and Karin Jurkat‐Rott , Myotonic disorders , Myopathies , 10.1016/S0072-9752(07)86003-9 , (61-76) , (2007) . J.G. McGivern and J.F.[doi.org]
Foot Pain
  • Abstract An 18-year-old male runner was referred to the authors' clinic with a 1-year history of cramping left foot pain.[ncbi.nlm.nih.gov]
Onset in Infancy
  • Conversely, only two of seven affected members of the Korean family had onset in infancy, while the other five patients had a more typical onset towards the end of the first decade. Most striking was the difference in frequency of the episodes.[doi.org]
  • In addition to the proband (IV-2), 5 members of her family (III-I, III-4, III-6, IV-3, and IV-4) interviewed experienced cold-induced muscle stiffness in their faces and hands with onsets in infancy, and 3 other members (I-2, II-2, and II-3) were thought[doi.org]

Workup

Evaluation for paramyotonia congenita includes a medical history of the patient as well as his/her family, physical examination, and neuromuscular testing. Myotonia will worsen with repeated or prolonged movement and then ultimately resolve after a period of minutes to days [1]. Symptoms are worsened by exposure to cold temperatures [2]. Patients may provide a history of anesthetic complications [5]. The patient's family history will often reveal similar symptoms or "cold intolerance" in relatives. Hypertrophy of affected muscles may be present in adults.

Tests commonly used to establish a diagnosis of paramyotonia congenita include:

  • Genetic analysis - Mutations of the SCN4A gene can be confirmed by genetic testing. A mutation of this gene confirms the diagnosis of paramyotonia congenita [6].
  • Electromyography (EMG) - EMG findings facilitate differentiation between paramyotonia congenita and myotonia congenita [7] [8]. In patients with paramyotonia congenita, EMG will show diffuse myotonic discharges, which are more pronounced with cooling of the affected muscles, as well as a total absence of muscle contractures with progressive cooling [9].
  • Muscle cooling - Lowering a temperature of affected muscles to 20-25°C induces muscle paralysis and stiffness, which persists even after rewarming. Exercise while the muscle is cooled results in exacerbation of muscle weakness and decreased compound muscle action potentials [10].
  • Exercise test - Exercise test is performed to confirm periodic paralysis. A positive test is characterized by two key findings in affected muscles: compound muscle action potentials are decreased and weakening of the muscle with exercise [11].
  • Muscle biopsy - A muscle biopsy showing vacuoles confirms the presence of non-specific myopathy [12] [6]; however, it does not confirm a diagnosis of paramyotonia congenita.

Laboratory tests do not confirm the diagnosis of paramyotonia congenita, but may help rule out other conditions. Patients with paramyotonia congenita may have a normal or slightly elevated creatine kinase level and/or normal or increased potassium level [13] [14] [15].

Treatment

  • Thiazide treatment in these two patients was ineffective. All seven patients responded well to tocainide. Treatment response and side effects were dose-dependent.[ncbi.nlm.nih.gov]
  • Pushpa Narayanaswami , Treatment and Management of Disorders of Neuromuscular Hyperexcitability , Neuromuscular Disorders: Treatment and Management , 10.1016/B978-1-4377-0372-6.00017-7 , (285-306) , (2011) . Satish V. Khadilkar, R.K. Singh, K.A.[doi.org]
  • Abstract Treatment of paramyotonia congenita with acetazolamide has been shown to reduce myotonic symptoms but severe weakness has developed in some patients leading to a recommendation not to use the drug in this disorder.[ncbi.nlm.nih.gov]
  • A patient with paramyotonia congenita, a related disorder with myotonia and episodic weakness, was studied during treatment with acetazolamide.[ncbi.nlm.nih.gov]
  • The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.[orpha.net]

Prognosis

  • Prognosis - Paramyotonia congenita The \'prognosis\' of Paramyotonia congenita usually refers to the likely outcome of Paramyotonia congenita.[checkorphan.org]
  • Prognosis Paramyotonia congenita has an excellent prognosis.[encyclopedia.com]
  • Paramyotonia congenita has an excellent prognosis.[medigoo.com]
  • CLINICAL COURSE/PROGNOSIS DM1 16: Patients with more severe cases may be severely affected with hypotonia, clubfoot, myopathic facies and dysphagia at birth.[now.aapmr.org]

Etiology

  • Because hyperkalemic periodic paralysis can occur in some families with PMC, it has been suggested that the 2 diseases share a common etiologic basis.[doi.org]
  • The overlap between various syndromes and etiologies can be confusing.[now.aapmr.org]

Epidemiology

  • PMC has not previously been described in Denmark and an epidemiological description of the family is given.[ncbi.nlm.nih.gov]
  • Epidemiology Paramyotonia congenita is considered an extremely rare disorder, though little epidemiological work has been done. Prevalence is generally higher in European derived populations and lower among Asians.[muscle-diseas.blogspot.com]
  • Epidemiological estimates have been provided for the German population. Here, it was estimated that the prevalence of PC is between 1:350,000 (0.00028%) and 1:180,000 (0.00056%).[medigoo.com]
  • Epidemiological estimates have been provided for the German population.[chemeurope.com]
Sex distribution
Age distribution

Pathophysiology

  • Emphasis has been placed on the diagnosis and management of these disorders rather than on their pathophysiology.[books.google.com]
  • Ruben , Physiology and Pathophysiology of Sodium Channel Inactivation , Na Channels from Phyla to Function , 10.1016/bs.ctm.2016.04.001 , (479-509) , (2016) . W. David Arnold, Daniel H.[doi.org]
  • Rüdel , Molecular pathophysiology of voltage-gated ion channels , Reviews of Physiology Biochemistry and Pharmacology, Volume 128 , 10.1007/3-540-61343-9_9 , (195-268) , (2005) . S.H.[doi.org]
  • Pathophysiologic and anesthetic considerations for patients with myotonia congenita or periodic paralyses . Paediatr Anaesth 2013 ; 23: 824 – 833 . Google Scholar Medline[journals.sagepub.com]
  • Rüdel , Molecular pathophysiology of voltage-gated ion channels , Reviews of Physiology Biochemistry and Pharmacology, Volume 128 , 10.1007/3-540-61343-9_9 , (195-268) , (2005) . Alfred L.[doi.org]

Prevention

  • Tocainide prevented myotonia and weakness induced by cooling, but failed to prevent hyperkalemic weakness. Hydrochlorothiazide prevented hyperkalemic weakness, but did not influence symptoms evoked by cooling.[ncbi.nlm.nih.gov]
  • Membrane repolarization, produced by a K channel opener, partly prevented and antagonized the drop in twitch force.[ncbi.nlm.nih.gov]
  • Efforts should be made to prevent perioperative attacks of muscle weakness when planning anesthesia for patients with this kind of disorder.[ncbi.nlm.nih.gov]
  • Depolarization could be prevented by the application of tetrodotoxin, a finding suggesting a defect in the Na channels.[ncbi.nlm.nih.gov]
  • The decrease of the resting potential and the changes in the current-voltage relationship at 27 degrees C could be prevented by the use of the Na channel blocker tetrodotoxin (TTX) or by bathing the fibers in a Na-free solution.[ncbi.nlm.nih.gov]

References

Article

  1. Baxter DW, Dyck PJ. Paramyotonia Congenita. Can Med Assoc J. 1961;85:113.
  2. Hahn C, Salajegheh MK. Myotonic disorders: A review article. Iran J Neurol. 2016;15:46-53.
  3. Matthews E, Tan SV, Fialho D, et al. What causes paramyotonia in the United Kingdom? Common and new SCN4A mutations revealed. Neurology. 2008;70:50–53.
  4. Bernard G, Shevell MI. Channelopathies: a review. Pediatr Neurol. 2008;38:73–85.
  5. Trivedi JR, Bundy B, Statland J, et al. Non-dystrophic myotonia: prospective study of objective and patient reported outcomes. Brain. 2013;136(Pt 7):2189–2200.
  6. Miller TM, Dias da Silva MR, Miller HA, et al. Correlating phenotype and genotype in the periodic paralyses. Neurology. 2004;63:1647–1655.
  7. Subramony S, Malhotra C, Mishra S. Distinguishing paramyotonia congenita and myotonia congenita by electromyography. Muscle Nerve. 1983;6: 374–379.
  8. Streib E, Russell JM, Douglass M, et al. Evoked response testing in myotonic syndromes. Muscle Nerve. 1984;7:590–592.
  9. Nielsen VK, Friis ML, Johnsen T. Electromyographic distinction between paramyotonia congenita and myotonia congenita: effect of cold. Neurology. 1982;32:827–832.
  10. Streib EW. AAEE minimonograph #27: Differential diagnosis of myotonic syndromes. Muscle Nerve. 1987;10:603-615.
  11. Hoffman EP, Lehmann-Horn F, Rudel R. Overexcited or inactive: ion channels in muscle disease. Cell. 1995;80:681–686.
  12. Thrush DC, Morris CJ, Salmon MV. Paramyotonia congenita: a clinical, histochemical and pathological study. Brain. 1972;95:537–552.
  13. Haass A, Ricker K, Rudel R, et al. Clinical study of paramyotonia congenita with and without myotonia in a warm environment. Muscle Nerve. 1981;4:388–395.
  14. Thrush DC, Morris CJ, Salmon MV. Paramyotonia congenita: a clinical, histochemical and pathological study. Brain. 1972;95:537–552.
  15. Matsumura T Saito T, Yonemoto N, et al. Renal dysfunction can be a common complication in patients with myotonic dystrophy. Neurol Sci. 2016;368:266-271.

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Last updated: 2018-06-22 00:56