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].

• Difficulty Walking

  walking Vasculitis Pain, weakness, numbness of arms and legs Metabolic Diseases of Muscle Symptoms Acid maltase deficiency Muscle weakness, dark-colored urine myoglobinuria, elevated CK or CPK, muscle fatigue, muscle cramps Carnitine deficiency Carnitine [nationwidechildrens.org]

• Perineal Pain

  However rarely this may result in tethered spinal cord syndrome caused by abnormal tissue attachments and traction of the cord within the spinal column. [3] Symptoms may vary including leg or perineal pains, weakness, sensory deficits, sphincter dysfunction [bmcanesthesiol.biomedcentral.com]

• Dyspnea

  […] limbs and myotonia 5 Myotonic dystrophy Systemic features Ocular : Cataract, ptosis, retinal degeneration Cardiac:Conduction disease, arryhtmias,cardiomyopathy Gastrointestinal: Dysphagia, colonic dysmotility, megacolon Diaphragmatic weakness can cause dyspnea [symptoma.com]

  However, when the patient was extubated following surgery, she exhibited acute dyspnea in the operating room and was immediately re-intubated and transferred to the intensive care unit. [link.springer.com]

  Novel mutation in KCNA1 causes episodic ataxia with paroxysmal dyspnea. Muscle and Nerve Volume 37, Issue 3, March 2008, Pages 399-402 Trip J, Drost G, van Engelen BGM, Faber CG. Drug treatment for myotonia. [now.aapmr.org]

• Myopathy

  Hyperthyroid myopathy and hypothyroid myopathy affect different muscles in different ways. [healthofchildren.com]

  ENDOCRINE MYOPATHIES Endocrine myopathies can occur when a gland produces too much or too little of a hormone. [web.archive.org]

  MDA supports ongoing research into the molecular bases of inherited myopathies and to find effective treatments. For more, see Research. [mda.org]

  G71.20 Congenital myopathy, unspecifed G71.22 Centronuclear myopathy G71.220 X-linked myotubular myopathy G71.228 Other centronuclear myopathy G71.29 Other congenital myopathy G71.3 Mitochondrial myopathy, not elsewhere classified G71.8 Other primary [icd10data.com]

• Myalgia

  Feeding difficulties Dysphagia Neonatal hypotonia Myalgia [mendelian.co] Swallowing difficulty [ more ] 0002015 Facial muscle hypertrophy Increased size of facial muscles Large facial muscles [ more ] 0012892 Feeding difficulties Feeding problems Poor [symptoma.com]

  PARAMYOTONIA CONGENITA WITHOUT COLD PARALYSIS, INCLUDED Classification genetic, neurological Phenotypes Autosomal dominant inheritance ; Feeding difficulties ; Handgrip myotonia ; Infantile onset ; Inspiratory stridor ; Muscle stiffness ; Muscle weakness ; Myalgia [mousephenotype.org]

  […] dystrophy type I (DM1, Curschmann-Steinert disease) Myotonic dystrophy type II (DM2, proximal myotonic myopathy) Clinical features Myotonia: delayed muscle relaxation following normal muscle contraction Skeletal muscle weakness(due to muscle atrophy) Myalgia [amboss.com]

  Genes related to Paramyotonia Congenita Of Von Eulenburg SCN4A View recommended genes panels Clinical Features Top most frequent phenotypes and symptoms related to Paramyotonia Congenita Of Von Eulenburg Feeding difficulties Dysphagia Neonatal hypotonia Myalgia [mendelian.co]

  Early reports suggested that patients with myoadenylate deaminase deficiency had various forms of myalgia, and exercise intolerance. [scielo.br]

• Spinal Cord Syndrome

  However rarely this may result in tethered spinal cord syndrome caused by abnormal tissue attachments and traction of the cord within the spinal column. [3] Symptoms may vary including leg or perineal pains, weakness, sensory deficits, sphincter dysfunction [bmcanesthesiol.biomedcentral.com]

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].

Evaluated in two adult patients refractory to other treatments and administered at a rate of one 0.5 mg tablet twice a day, the treatment was very conclusive both clinically and electrophysiologically, at four weeks apart. [institut-myologie.org]

Treatment Some patients do not require treatment to manage the symptoms of paramyotonia congenita. Others, however, require treatment for their muscle stiffness and often find mexiletine to be helpful. [checkorphan.org]

Treatment team Paramyotonia congenita is diagnosed and treated by neurologists. Treatment Paramyotonia congenita is usually mild enough not to require any treatment at all. [encyclopedia.com]

There are currently no FDA approved treatments for this disorder. [n.neurology.org]

Description Recent advances in the understanding of myotonia congenita have identified potential areas that could possibly respond to treatment in a drug study. [centerwatch.com]

Prognosis The 'prognosis' of Paramyotonia congenita usually refers to the likely outcome of Paramyotonia congenita. [checkorphan.org]

[diseaseinfosearch.org] Prognosis Prognosis The 'prognosis' of Paramyotonia congenita usually refers to the likely outcome of Paramyotonia congenita. [checkorphan.org] Prognosis Paramyotonia congenita has an excellent prognosis. [symptoma.com]

Prognosis Paramyotonia congenita has an excellent prognosis. [encyclopedia.com]

[doi.org] The overlap between various syndromes and etiologies can be confusing. [symptoma.com]

Many etiologies result in myotonia, including dystrophic and non-dystrophic myotonias. [statpearls.com]

[…] phosphorylation to generate the… Expand BackgroundThe recent development and spread of ultrasonography and ultrasonography-guided fine needle aspiration biopsy (FNAB… Expand Ulcerative colitis is a common form of inflammatory bowel disease with a complex etiology [semanticscholar.org]

ETIOLOGY:- The presentation of myotonia can result from a diverse array of etiologies. [samarpanphysioclinic.com]

Cases of severe denervation of any etiology.8 The rest of this article will focus on the true primary myotonic disorders. [now.aapmr.org]

[dovemed.com] Epidemiology PMC has not previously been described in Denmark and an epidemiological description of the family is given. [symptoma.com]

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. [findzebra.com]

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]

[medigoo.com] 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. [symptoma.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]

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]

This pathophysiological mechanism can lead to an initial burst of myotonia discharges and result in the symptom of stiffness. [tandfonline.com]

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]

Google Scholar Medline [journals.sagepub.com] Prevention Tocainide prevented myotonia and weakness induced by cooling, but failed to prevent hyperkalemic weakness. [symptoma.com]

Beginning in infancy or early childhood, people with this condition experience bouts of sustained muscle tensing (myotonia) that prevent muscles from relaxing normally. [raregenomics.org]

Treatment may prevent, and may even reverse, progressive muscle weakness. [nlm.nih.gov]

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