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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].

Italian
  • The authors describe an Italian kindred with nine individuals affected by hyperkalaemic periodic paralysis associated with paramyotonia congenita (hyperPP/PMC).[ncbi.nlm.nih.gov]
  • Center for Neurological and Neuromuscular Rare Disease, Università degli Studi della Campania Luigi Vanvitelli , Napoli , Campania , Italy 3 Molecular Genetics and Genomics Laboratory , Institute of Genetics and Biophysics, Adriano Buzzati Traverso, Italian[jnnp.bmj.com]
  • Meola, Mutation in the S4 segment of the adult skeletal sodium channel gene in an Italian Paramyotonia Congenita (PC) family, The Italian Journal of Neurological Sciences, 10.1007/BF02334608, 15, 9, (473-480), (1994). Franklin H. Epstein, Louis J.[doi.org]
Myopathy
  • 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]
Proximal Muscle Weakness
  • On the basis of clinical findings in this family, persistent proximal muscle weakness, myopathic EMG abnormalities, a type IIB atrophy on muscle biopsy and no symptoms but other signs of muscle affection, were earlier suggested as clinical features of[ncbi.nlm.nih.gov]
  • Mild proximal muscle weakness was evident in adult family members without obvious muscle wasting.[doi.org]
Muscle Contracture
  • 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.[symptoma.com]
Foot Pain
  • 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]
Vertigo
  • Thomas Brandt, Familial periodic ataxia/vertigo (episodic ataxia), Vertigo, 10.1007/978-1-4471-0527-5_25, (365-374), (1999).[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]
  • There is no cure for this disease and treatment usually includes avoiding activities that lead to symptoms. If your child has been diagnosed with paramyotonia congenita, talk to their doctor about all treatment options.[diseaseinfosearch.org]

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]
  • […] the sodium channel disorder described here should be considered in patients with the symptoms described — especially as the symptoms respond to treatments such as acetazolamide and mexiletine, and as there are implications for genetic counselling and prognosis[mja.com.au]

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.[ipfs.io]
  • 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]
Sex distribution
Age distribution

Pathophysiology

  • 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]
  • Emphasis has been placed on the diagnosis and management of these disorders rather than on their pathophysiology.[books.google.com]
  • Abstract An important question in the pathophysiology of dominantly inherited diseases, such as channelopathies, is the level of expression of the mutant protein.[ncbi.nlm.nih.gov]
  • Pathophysiologic and anesthetic considerations for patients with myotonia congenita or periodic paralyses . Paediatr Anaesth 2013 ; 23: 824 – 833 . Google Scholar Medline[journals.sagepub.com]

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]
  • Avoidance of myotonia triggering events is also an effective method of mytonia prevention. Resources - Paramyotonia congenita Not supplied.[checkorphan.org]

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: 2019-07-11 20:53