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Ion Channel Myopathy

Ion channel myopathies are a heterogeneous group of disorders that are caused by genetic defects in sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia, chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes, and calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes ion channels Channels The Cell: Cell Membrane in the myocyte membranes resulting in myotonia. These myopathies present clinically with symptoms of muscle pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, weakness, stiffness, cramps, and spasm. Diagnosis is made on the basis of clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor, lab testing, electromyography Electromyography Recording of the changes in electric potential of muscle by means of surface or needle electrodes. Becker Muscular Dystrophy, and genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies. Management involves both prevention with diet and exercise modifications and treatment with diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication in some cases.

Last updated: 10 Sep, 2021

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Ion channel myopathies are a heterogeneous group of disorders that are caused by genetic defects in sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia, chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes, and calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes ion channels Channels The Cell: Cell Membrane in the myocyte membranes resulting in myotonia.

Classification, epidemiology, and pathophysiology

  • Myotonia congenita: 2 forms based on patterns of transmission
    • Both forms are due to mutations in the CLCN1 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics.
    • Becker form: autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance (not the same as Becker muscular dystrophy Muscular Dystrophy Becker Muscular Dystrophy)
      • Onset: ages 4–12 as general muscle stiffness
      • More common and severe, generalized form
    • Thomsen form: autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance
      • Onset: infancy to age 3
      • Rare and milder form
    • Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency is unknown.
    • Pathophysiology: defect in chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes channels Channels The Cell: Cell Membrane → decreased conductance of chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes into the muscle cell → slowed repolarization Repolarization Membrane Potential of the cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane
  • Hypokalemic periodic paralysis: most common type of periodic paralysis (PP)
    • Onset: late childhood to teenage years
    • Autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance disease 
    • Gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics mutations:
      • Most commonly (70%) CALCL1A gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics: codes for the alpha-1 subunit of the dihydropyridine-sensitive calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel in skeletal muscle
      • Less commonly SCN4A: affects sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia ion channels Channels The Cell: Cell Membrane
    • Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: 1 in 100,000
    • Clinical expression: men > women
    • Pathophysiology: triggering events → increased release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of epinephrine Epinephrine The active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. Sympathomimetic Drugs or insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin → intracellular potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia shift → hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia
  • Hyperkalemic PP:
    • Onset: 1st decade of life
    • Rare autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance disease 
    • Gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in SCN4A that regulates the production of a protein in the sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia channel in skeletal muscle
    • Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: 1 in 200,000
    • Clinical expression: equal in the 2 sexes
    • Pathophysiology:  
      • Normally, the sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia channel is closed in the resting phase Resting phase Skin: Structure and Functions after normal muscle contraction.
      • With hyperkalemic PP, the Na channel closes too slowly →  sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia ions continue to leak into the muscle cell →  myotonia (muscle stiffness)
      • If the channel remains open → muscle becomes desensitized → paralysis → potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia ions are released from the muscle → hyperkalemia Hyperkalemia Hyperkalemia is defined as a serum potassium (K+) concentration >5.2 mEq/L. Homeostatic mechanisms maintain the serum K+ concentration between 3.5 and 5.2 mEq/L, despite marked variation in dietary intake. Hyperkalemia can be due to a variety of causes, which include transcellular shifts, tissue breakdown, inadequate renal excretion, and drugs. Hyperkalemia

Clinical Presentation and Diagnosis

Symptoms and presentations can appear similar in different ion channel myopathies, making lab testing essential for diagnosis before treatment.

Clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor

Table: Comparison of clinical presentations of ion channel myopathy Myopathy Dermatomyositis
Myotonia congenita Hypokalemic periodic paralysis Hyperkalemic periodic paralysis
  • Symptoms vary between individuals.
  • Myotonia in 80%–99%
  • Myalgia in 5%–29%
  • < 5% will have muscle stiffness, weakness, percussion Percussion Act of striking a part with short, sharp blows as an aid in diagnosing the condition beneath the sound obtained. Pulmonary Examination myotonia, or skeletal muscle hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation.
  • Warm-up effect: Stiffness is usually painless and can be relieved by exercise.
  • No cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) involvement, as seen with myotonic dystrophy
  • Myotonia with relapsing episodes of hypotonic Hypotonic Solutions that have a lesser osmotic pressure than a reference solution such as blood, plasma, or interstitial fluid. Renal Sodium and Water Regulation paralysis
  • Lid lag: earliest finding
  • Proximal muscle groups more affected than distal muscle groups
  • Severe attacks can result in complete paralysis.
  • Occurs a few times per year; typically lasts for hours to days
  • No or minimal bulbar/respiratory involvement
  • Progressive proximal myopathy Myopathy Dermatomyositis eventually develops after age 50.
  • Weakness or paralysis of muscles in the hips, shoulders, and back
  • > 50% present before age 10
  • Normal sensation
  • May develop fixed proximal weakness
  • Attacks are rarely severe.
  • Occasional pseudohypertrophy of muscles
  • Can occur several times per day
  • Symptoms last for minutes to hours.
Triggers Triggers Hereditary Angioedema (C1 Esterase Inhibitor Deficiency):
  • Vigorous exercise
  • Fasting or other stress
  • High-carbohydrate meals
Triggers Triggers Hereditary Angioedema (C1 Esterase Inhibitor Deficiency):
  • Rest after exercise
  • Fasting or other stress
  • Ingesting potassium-rich food
  • Low-carbohydrate diet
  • Cold exposure Exposure ABCDE Assessment
  • Anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts

Diagnosis

  • For hypokalemic PP: Lab results show ↓ serum K+ level during an attack.
  • For hyperkalemic PP: Lab results show ↑ serum K+ levels.
  • For both forms of PP:
    • Myotonia on exam and/or electromyography Electromyography Recording of the changes in electric potential of muscle by means of surface or needle electrodes. Becker Muscular Dystrophy (EMG) during attacks
    • Family history Family History Adult Health Maintenance is important
    • Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies
    • Thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy function tests should be done.
    • Provocative tests and muscle biopsies are not recommended.
  • For myotonia congenita: clinical suspicion confirmed with genetic studies
    • Muscle biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma: no signs of dystrophy
    • Labs: CK levels may be elevated.
    • EMG: shows myotonic discharge

Management

Brief flare-ups of symptoms may not need treatment and can resolve with exercise or rest, depending on the disorder and the etiology of the attack.

  • Myotonia congenita:
    • Exercise may temporarily help the myotonia.
    • Medications to treat muscle stiffness:
      • Mexiletine Mexiletine Antiarrhythmic agent pharmacologically similar to lidocaine. It may have some anticonvulsant properties. Class 1 Antiarrhythmic Drugs (Sodium Channel Blockers)
      • Carbamazepine Carbamazepine A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal seizures. It may also be used in the management of bipolar disorder, and has analgesic properties. First-Generation Anticonvulsant Drugs
      • Phenytoin Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. First-Generation Anticonvulsant Drugs
    • Caution with increased risk of harmful side effects of anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts
    • Relatives should be tested during childhood.
  • Hypokalemic PP: 
    • Treatment of attacks:
      • Confirm potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia level before starting treatment.
      • Normalize serum K+ with oral K+ supplement.
      • IV potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia if arrhythmias present; should not be administered in solutions containing dextrose Dextrose Intravenous Fluids because of exaggerated insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin response to carbohydrate loads → hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia
    • Prevention:
      • Low-carbohydrate diet
      • Refrain from vigorous exercise.
    • Medications:
      • Oral K+ supplementation
      • K+-sparing diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication (e.g., spironolactone Spironolactone A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. Potassium-sparing Diuretics)
      • Carbonic anhydrase inhibitors Carbonic anhydrase inhibitors Carbonic anhydrase inhibitors (CAIs) block the carbonic anhydrase enzymes in the proximal convoluted tubule, inhibiting the reabsorption of sodium bicarbonate (NaHCO3), which results in diuresis and metabolic acidosis. Carbonic Anhydrase Inhibitors (e.g., acetazolamide Acetazolamide One of the carbonic anhydrase inhibitors that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. Carbonic Anhydrase Inhibitors)
  • Hyperkalemic PP:
    • Treatment of attacks:
      • Mild physical exercise
      • High-carbohydrate snack/sugar
      • IV calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes gluconate
    • Prevention:
    • Medications:
      • Thiazide diuretics Thiazide diuretics Thiazide and thiazide-like diuretics make up a group of highly important antihypertensive agents, with some drugs being 1st-line agents. The class includes hydrochlorothiazide, chlorothiazide, chlorthalidone, indapamide, and metolazone. Thiazide Diuretics
      • Carbonic anhydrase inhibitors Carbonic anhydrase inhibitors Carbonic anhydrase inhibitors (CAIs) block the carbonic anhydrase enzymes in the proximal convoluted tubule, inhibiting the reabsorption of sodium bicarbonate (NaHCO3), which results in diuresis and metabolic acidosis. Carbonic Anhydrase Inhibitors
      • Inhaled beta-agonists as needed

Differential Diagnosis

  • Andersen-Tawil syndrome Andersen-Tawil syndrome A form of inherited long QT syndrome (or LQT7) that is characterized by a triad of potassium-sensitive periodic paralysis, ventricular ectopic beats, and abnormal features such as short stature, low-set ears, and scoliosis. It results from mutations of KCNJ2 gene which encodes a channel protein that regulates resting membrane potential. Long QT Syndrome: rare genetic disorder associated with a mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations of the KCNJ2 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics causing an ion defect in the potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia channel. Andersen-Tawil syndrome Andersen-Tawil syndrome A form of inherited long QT syndrome (or LQT7) that is characterized by a triad of potassium-sensitive periodic paralysis, ventricular ectopic beats, and abnormal features such as short stature, low-set ears, and scoliosis. It results from mutations of KCNJ2 gene which encodes a channel protein that regulates resting membrane potential. Long QT Syndrome is characterized by a triad of symptoms that include episodes of muscle weakness and paralysis, arrhythmias, and distinctive facial and skeletal features. The diagnosis is made clinically with confirmatory genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies. There is no standard protocol for treatment, but prevention with carbonic anhydrase inhibitors Carbonic anhydrase inhibitors Carbonic anhydrase inhibitors (CAIs) block the carbonic anhydrase enzymes in the proximal convoluted tubule, inhibiting the reabsorption of sodium bicarbonate (NaHCO3), which results in diuresis and metabolic acidosis. Carbonic Anhydrase Inhibitors is used.
  • Myotonic dystrophy: Myotonic dystrophy types 1 and 2 are autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance heterogeneous diseases that primarily affect Affect The feeling-tone accompaniment of an idea or mental representation. It is the most direct psychic derivative of instinct and the psychic representative of the various bodily changes by means of which instincts manifest themselves. Psychiatric Assessment the muscles, but unlike other muscular dystrophies, they have multisystem effects. Both types present with myotonia, muscle weakness, and myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus; however, type 1 Type 1 Spinal Muscular Atrophy is severe and carries a reduced life expectancy Life expectancy Based on known statistical data, the number of years which any person of a given age may reasonably expected to live. Population Pyramids, whereas type 2 Type 2 Spinal Muscular Atrophy is mild, with a normal life expectancy Life expectancy Based on known statistical data, the number of years which any person of a given age may reasonably expected to live. Population Pyramids. Diagnosis is made clinically, with genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies, and by EMG. Management is primarily supportive.
  • Paramyotonia congenita: rare congenital Congenital Chorioretinitis autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance form of myotonia caused by sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia channel mutations in the SCN4A gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics. Paramyotonia congenita is described as paradoxical in that the myotonia becomes worse with exercise and is considered by some to be the same disorder as hyperkalemic periodic paralysis. It typically presents before age 10 with muscle stiffness in the face or upper extremities. Diagnosis is clinical, and distinction from other myotonias is by EMG and genomic sequencing.
  • Myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis (MG): autoimmune neuromuscular disorder caused by dysfunction/destruction of acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors. Myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis presents with fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, ptosis Ptosis Cranial Nerve Palsies, diplopia Diplopia A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. Myasthenia Gravis, and progressive weakness in the limbs, typically occurring with milder degrees of exertion than PP, and does not occur in “attacks.” Myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis often involves bulbar and extraocular muscles, which are rarely, if ever, affected in hyperkalemic PP. Diagnosis is based on clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor, detection of antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions, and electrophysiologic studies. Management involves increasing the activity of acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS at the neuromuscular junction Neuromuscular junction The synapse between a neuron and a muscle. Skeletal Muscle Contraction.
  • Thyrotoxic periodic paralysis ( TPP TPP Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition due to either a congenital or an acquired deficiency of ADAMTS-13, a metalloproteinase that cleaves multimers of von Willebrand factor (VWF). The large multimers then aggregate excessive platelets resulting in microvascular thrombosis and an increase in consumption of platelets. Thrombotic Thrombocytopenic Purpura): form of hypokalemic periodic paralysis. Thyrotoxic periodic paralysis most commonly presents as sudden-onset weakness in the proximal muscles after age 20. The diagnosis is made clinically and with lab testing for thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy function. Management is by maintaining a euthyroid Euthyroid Thyroiditis state, and preventive treatment with beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers) is used.

References

  1. Statland JM, et al. (2018). Review of the diagnosis and treatment of periodic paralysis. Muscle Nerve 57:522–530. DOI: 10.1002/mus.26009
  2. Neki NS. (2016). Hyperthyroid hypokalemic periodic paralysis. Pakistan Journal of Medical Sciences, vol. 32, no. 4, 2016, pp. 1051–52. PubMed Central. https://pubmed.ncbi.nlm.nih.gov/27648066/
  3. Ceccato F, Scaroni C. (2019). Central adrenal insufficiency: open issues regarding diagnosis and glucocorticoid treatment. Clinical Chemistry and Laboratory Medicine 57:1125–1135. https://doi.org/10.1515/cclm-2018-0824
  4. Lacomis D. (2019). Myopathies of systemic disease. UpToDate. Retrieved August 26, 2021, from https://www.uptodate.com/contents/myopathies-of-systemic-disease
  5. Taminato T, et al. (2020). Paramyotonia congenita with persistent distal and facial muscle weakness: a case report with literature review. Journal of Neuromuscular Diseases 7:193–201. DOI: 10.3233/JND-190440
  6. Gutmann L, Conwit R. (2021). Hyperkalemic periodic paralysis. UpToDate. Retrieved August 26, 2021, from https://www.uptodate.com/contents/hyperkalemic-periodic-paralysis
  7. Genetic and Rare Diseases Information Center (GARD). (2017). Myotonia congenita. Retrieved August 26, 2021, from https://rarediseases.info.nih.gov/diseases/12301/myotonia-congenita

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