Prevalence study of genetically defined skeletal muscle channelopathies in England

Horga, Alejandro; Rayan, D.L. Raja; Matthews, Emma; Sud, Richa; Fialho, Doreen; Durran, S.; Burge, J.; Portaro, Simona; Davis, Mary B.; Haworth, Andrea; Hanna, Michael G.

doi:10.1212/wnl.0b013e31828cf8d0

Cited by 112 publications

(99 citation statements)

References 12 publications

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“…Muscle fiber excitability is usually preserved at baseline, but the channel defects predispose individuals to paroxysmal attacks of muscle stiffness (myotonia from pathologically enhanced excitability) or intermittent failure of excitability resulting in severe weakness (periodic paralysis). These rare disorders have a prevalence of about 1 : 100,000 (106). Most are inherited in a Mendelian pattern as autosomal dominant traits, and most affect only skeletal muscle without defects of heart, peripheral nerve, or the central nervous system.…”

Section: Introductionmentioning

confidence: 99%

Channelopathies of Skeletal Muscle Excitability

Cannon

2015

Comprehensive Physiology

176

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Familial disorders of skeletal muscle excitability were initially described early in the last century and are now known to be caused by mutations of voltage-gated ion channels. The clinical manifestations are often striking, with an inability to relax after voluntary contraction (myotonia) or transient attacks of severe weakness (periodic paralysis). An essential feature of these disorders is fluctuation of symptoms that are strongly impacted by environmental triggers such as exercise, temperature, or serum K+ levels. These phenomena have intrigued physiologists for decades, and in the past 25 years the molecular lesions underlying these disorders have been identified and mechanistic studies are providing insights for therapeutic strategies of disease modification. These familial disorders of muscle fiber excitability are “channelopathies” caused by mutations of a chloride channel (ClC-1), sodium channel (NaV1.4), calcium channel (CaV1.1) and several potassium channels (Kir2.1, Kir2.6, Kir3.4). This review provides a synthesis of the mechanistic connections between functional defects of mutant ion channels, their impact on muscle excitability, how these changes cause clinical phenotypes, and approaches toward therapeutics.

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Section: Introductionmentioning

confidence: 99%

Channelopathies of Skeletal Muscle Excitability

Cannon

2015

Comprehensive Physiology

176

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“…Hyperkalaemic periodic paralysis (hyperPP) is a rare entity of muscle weakness disease with a prevalence of 0.17 per 100 000 1. It is due to SCN4A gene mutation resulting in a defect in skeletal muscle sodium channels 2.…”

Section: Introductionmentioning

confidence: 99%

Hyperkalaemic periodic paralysis in pregnancy

Yong

Sin

Tang³

et al. 2018

BMJ Case Reports

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Hyperkalaemic periodic paralysis is a rare skeletal muscle disorder which is characterised by episodic muscle paralysis associated with hyperkalaemia. Although it is an autosomal-dominant disease, cases of de novo mutations have been reported. We report the case of a 30-year-old woman, gravida 5 para 3+1, who was planned for an elective repeated caesarean section at 38 weeks and 3 days of pregnancy. She developed recurrent episodes of hyperkalaemic periodic paralysis after receiving corticosteroids. Intravenous calcium gluconate was administered to normalise potassium levels (from 6.3 mmol/L to 4.1 mmol/L). Extra anaesthetic precautions were taken during the caesarean delivery. Postoperatively, she was well and discharged from the ward. She encountered similar symptoms in her third pregnancy, and there was no family history of muscle weakness which suggested a de novo mutation. Pregnancy seemed to result in vulnerability to hyperkalaemic attacks as she was never symptomatic outside pregnancy.

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“…All three mechanisms are unified by destabilising the muscle membrane and leading to prolonged depolarisation. 10 The periodic paralyses are rare, the estimated point prevalence in England is: hyperkalemic periodic paralysis 0.17/100,000, hypokalemic periodic paralysis 0.13/100,000, and AndersenTawil syndrome (ATS) 0.08/100,000 11 .…”

Section: Introductionmentioning

confidence: 99%