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].

• Weakness

  For other patients, exercise consistently induces symptoms of myotonia and/or weakness. Typical presentations of this are during squating or repetitive fist clenching. [muscle-diseas.blogspot.com]

  Pure Paramyotonia: Consists of paramyotonia plus (in some but not all patients) episodic weakness which develops with exercise and chilling. Mild attacks cause stiffness, more severe ones cause weakness. [hkpp.org]

• Pain

  General Article Anesthesia and Pain Medicine 2014;9(4):298-300. Published online October 31, 2014. [anesth-pain-med.org]

  This is not painful, but is often misdiagnosed as thrush or as leukoplakia. Neurovascular Structures in Calluses (painful blood vessels or nerve endings). These can grow in the calluses and make trimming difficult and walking extra painful. [pachyonychia.org]

  At the 2009 PPA Conference, some patients with suspected HyperKPP/PMC complained of muscle pain during and after attacks. Therapy Paramyotonia congenita (PC) can present with one of two problems (or a combo of both). [periodicparalysis.org]

  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]

• Fatigue

  During brief exercise, overexcitation of muscles can cause stiffness, and with prolonged exercise, the overexcitation can occasionally lead to a fatigue-like weakness or even complete paralysis. [mda.org]

  Isometric twitch times did not alter significantly during this muscle fatigue. Cooling greatly accelerated the fatiguing process. [ncbi.nlm.nih.gov]

  We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: July 20, 2021 [patientslikeme.com]

• Falling

  Though exercise induced a mild fall in CMAP amplitude in both groups, postexercise fibrillations occurred only in patients with paramyotonia congenita. [ncbi.nlm.nih.gov]

  If activities like climbing stairs and walking long distances become very fatiguing it may be wise to use a chair to conserve physical strength and avoid falls. [hkpp.org]

  Striking feature is the sometimes generalized stiffness following a sudden surprise or startle resulting in a fall Muscle stiffness improves after repeated exercise (warm up phenomenon) Patients appear athletic and muscles are hypertrophied 9 Paramyotonia [slideplayer.com]

• 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]

• 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]

• Muscle Rigidity

  We examined the effects of propofol on a paramyotonia 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 [ncbi.nlm.nih.gov]

  In some families affected members have classical symptoms of PMC (muscle rigidity and weakness precipitated by cold and activity) without any other symptoms. But in other families affected members have attacks of both PMC and HyperKPP. [hkpp.org]

• Diarrhea

  […] doctor or other medical specialist, for example, a neurologist, will likely run some preliminary tests to rule in or rule out (called a differential diagnosis) other causes of muscle weakness such as licorice intoxication, laxative abuse, and/or severe diarrhea [medicinenet.com]

  It can cause severe diarrhea and can lead to symptoms that seem like Leigh Syndrome. Progressive External Ophthalmoplegia (PEO) causes the muscles in your eyes and eyelids to work incorrectly. [healthcare.utah.edu]

  Gastrointestinal complaints are also frequent and may be severe, often requiring GI specialist, speech therapist, and nutritionist input for dysphagia, constipation or diarrhea. [now.aapmr.org]

• Muscle Weakness

  CASE REPORT We report a family with a history of PC accompanied by persistent hand muscle weakness with masticatory muscle involvement. Persistent weakness was exacerbated with age, and MR analysis… Expand [semanticscholar.org]

  This condition causes patients to have myotonia attacks and muscle weakness attacks. People who have pure paramyotonia may have attacks of myotonia and weakness at the same time, or myotonia only, or weakness only. [periodicparalysis.org]

  There are also intermittent periods of a type of muscle weakness in which there is no muscle tone (flaccid paresis). [healthjade.net]

  It most often affects the muscles of the face and upper extremities. Though the paradoxical myotonia associated with Eulenburg disease can lead to muscle weakness, persistent weakness is not a symptom of this particular condition. [wisegeek.com]

  The Ile693Thr mutation of the skeletal muscle Na+ channel alpha-subunit is associated with an unusual phenotype of paramyotonia congenita characterized by cold-induced muscle weakness but no stiffness. [ncbi.nlm.nih.gov]

• Myopathy

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

  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]

• 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]

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

• Muscle Cramp

  DISCUSSION In 1978, Fishbein et al. described MAD deficiency in skeletal muscle of 5 patients with exercise-related muscle cramps, and myalgias2. [scielo.br]

  Symptoms Acid maltase deficiency Muscle weakness, dark-colored urine myoglobinuria, elevated CK or CPK, muscle fatigue, muscle cramps Carnitine deficiency Carnitine palmityl transferase deficiency Cytochrome oxidase deficiency Debrancher enzyme deficiency [nationwidechildrens.org]

  Common signs and symptoms include: Lack of muscle tone Muscle weakness Delayed motor skills Noticeable facial weakness Drooping eyelids Muscle cramps or contractions There are different types of congenital myopathies, some of which include: Central core [mayoclinic.org]

  […] contractions; fasciculation; hyporeflexia; muscle cramp; muscle weakness; hyperhidrosis; tachycardia; and myokymia. [icd10data.com]

• Painful Muscle Cramps

  Muscle Nerve 1983;6:143-8. 7. Sunohara N, Tomi H, Nakamura A, Arahata K, Nonaka I. Myotonia congenital with painful muscle cramps. Intern Med 1996;35:507-11. 8. Wadia RS, Amin RB, Prayag SV, Chanratare SN, Sardesai HV. [neurologyindia.com]

  Some people also experience muscle stiffness and painful muscle cramps. Severe cases can cause rhabdomyolysis. Sometimes, the disease causes muscle enlargement along with muscle weakness. [web.archive.org]

• Paresis

  Unfortunately, she suddenly presented a paresis of the left arm (dominant side) after a strong activity of crawl swimming. The clinical examination at day 3 showed a proximal paresis of the left arm. [ncbi.nlm.nih.gov]

• Clumsiness

  […] was no change in frequency2 PPP can have a significant impact on patients’ everyday lives1 Symptoms can persist after attacks have subsided: Patients have reported experiencing lingering symptoms, including weakness, extreme fatigue, muscle pain, and clumsiness [keveyis.com]

  I was called clumsy, lazy, and a hypochondriac. Once we asked a family physician why I was having so much trouble swallowing, and he said I had "Eve's Curse"... a little bit of the forbidden fruit stuck in my throat. [myotoniacongenita.org]

  On direct questioning, however, his parents reported that his movements appeared “clumsy” from the time he began to walk and that the symptoms related to his eyes were already present when he was an infant. [content.iospress.com]

  Children may appear clumsy and fall frequently, even after walking is established. Patients may also exhibit difficulty in opening eyes during prolonged contraction, such as crying. [statpearls.com]

• Slurred Speech

  It can cause slurred speech and temporarily cause your jaw to lock. Type 2 MMD (MMD2) is similar to type 1 MMD and shares most of the same symptoms. However, type 2 is usually less severe. [healthcare.utah.edu]

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/Management 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. [muscle-diseas.blogspot.com]

Treatment - Paramyotonia congenita 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]

Signs are generally mild and infrequent, and typically may not need treatment. If cold-induced myotonia is significant, avoidance of cold is recommended. [humpath.com]

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 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]

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]

[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]

[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]

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]

[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]

[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]

Pathophysiology Paramyotonia congenita (as well as hyperkalemic periodic paralysis and the potassium-aggravated myotonias) is caused by mutations in a sodium channel, SCN4A. The phenotype of patients with these mutations is indicated in Table 1. [muscle-diseas.blogspot.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]

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]

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

Avoidance of myotonia triggering events is also an effective method of mytonia prevention. Epidemiology Paramyotonia congenita is considered an extremely rare disorder, though little epidemiological work has been done. [muscle-diseas.blogspot.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]

Mexiletine is very effective in preventing and reducing the degree of cold-induced stiffness and weakness. Some paramyotonia congenita patients have taken it for decades and still use it. [periodicparalysis.org]

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.