Channelopathies are a group of disorders caused by dysfunctions in ion channels, which are proteins embedded in cell membranes that regulate the flow of ions (such as sodium, potassium, calcium, and chloride) across the membrane. These ion channels are crucial for various cellular processes, including generating electrical signals in nerve, muscle, and other excitable tissues.

Skeletal Muscle Channelopathies

• Periodic Paralyses
  • Hypokalemic Periodic Paralysis (HKPP)
    • Caused by mutations in CACNA1S (calcium channel gene)
    • Triggers: high carbohydrate meals, rest after exercise
  • Hyperkalemic Periodic Paralysis (HyperKPP)
    • Caused by mutations in SCN4A (sodium channel gene)
    • Triggers: fasting, exercise, potassium-rich foods
  • Andersen-Tawil Syndrome
    • Mutations in KCNJ2 (potassium channel gene)
    • Features: periodic paralysis, ventricular arrhythmias, dysmorphic features
• Congenital Myotonias
  • Thomsen Disease
    • Autosomal dominant mutation in CLCN1 (chloride channel gene)
    • Features: muscle stiffness without weakness
  • Becker Disease
    • Autosomal recessive mutation in CLCN1
    • Features: more severe myotonia than Thomsen disease
  • Paramyotonia Congenita
    • Caused by mutations in SCN4A
    • Features: cold-induced muscle stiffness
• Malignant Hyperthermia Susceptibility
  • Caused by mutations in RYR1 (ryanodine receptor) or CACNA1S
  • Triggered by volatile anesthetics or depolarizing muscle relaxants

Central Nervous System Channelopathies

• Epilepsy Syndromes
  • Generalized Epilepsy with Febrile Seizures Plus (GEFS+)
    • Mutations in SCN1A, SCN2A, or GABRG2
  • Dravet Syndrome
    • Caused by mutations in SCN1A
    • Features: intractable seizures, developmental delay
  • Benign Familial Neonatal Epilepsy
    • Mutations in KCNQ2 or KCNQ3 (potassium channels)
    • Features: self-limiting neonatal seizures
  • Childhood Absence Epilepsy
    • Associated with CACNA1H (calcium channel mutations)
• Migraine Syndromes
  • Familial Hemiplegic Migraine (FHM)
    • Type 1: CACNA1A mutation
    • Type 2: ATP1A2 mutation
    • Type 3: SCN1A mutation
• Ataxia Syndromes
  • Episodic Ataxia Type 1
    • Caused by KCNA1 (potassium channel mutation)
    • Features: ataxia with myokymia
  • Episodic Ataxia Type 2
    • Caused by CACNA1A mutation
    • Features: ataxia with vertigo
• Neurodevelopmental Disorders
  • KCNQ2 Encephalopathy
    • Mutations in KCNQ2 (potassium channel gene)
    • Features: early-onset epilepsy and severe developmental delay
  • SCN2A Encephalopathy
    • Mutations in SCN2A (sodium channel gene)
    • Features: severe epileptic encephalopathy

Cardiac Channelopathies

• Long QT Syndromes (LQTS)
  • LQT1: Mutations in KCNQ1 (potassium channel)
  • LQT2: Mutations in KCNH2 (potassium channel)
  • LQT3: Mutations in SCN5A (sodium channel)
• Brugada Syndrome
  • Mutations in SCN5A (sodium channel)
  • Features: ventricular arrhythmias, sudden cardiac death
• Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
  • Type 1: Mutations in RYR2 (ryanodine receptor)
  • Type 2: Mutations in CASQ2 (calcium-handling protein)
• Short QT Syndrome
  • Mutations in KCNH2, KCNJ2, or CACNA1C

Pain and Sensory Channelopathies

• Inherited Erythromelalgia
  • Mutations in SCN9A (sodium channel)
  • Features: severe burning pain triggered by warmth
• Paroxysmal Extreme Pain Disorder
  • Mutations in SCN9A
  • Features: episodic severe rectal, ocular, or jaw pain
• Congenital Insensitivity to Pain
  • Mutations in SCN9A or TRKA (nerve growth factor receptor)
  • Features: absence of pain perception
• Small Fiber Neuropathy
  • Associated with SCN9A or SCN10A mutations
  • Features: burning pain, dysautonomia

Endocrine Channelopathies

• Congenital Hyperinsulinism
  • Mutations in ABCC8 or KCNJ11 (potassium channels in beta cells)
  • Features: persistent hypoglycemia
• Familial Hypocalciuric Hypercalcemia
  • Mutations in CASR (calcium-sensing receptor)
• Bartter Syndrome
  • Type 1: Mutations in SLC12A1 (sodium-potassium-chloride cotransporter)
  • Type 3: Mutations in CLCNKB (chloride channel)

Other Channelopathies

• Cystic Fibrosis
  • Mutations in CFTR (chloride channel)
  • Features: pulmonary and gastrointestinal involvement
• Andersen-Tawil Syndrome
  • Potassium channelopathy with systemic features
• Hypomagnesemia
  • TRPM6/TRPM7 mutations affecting magnesium reabsorption