Clinical features
• Early infantile epileptic encephalopathy, characterized by the onset of tonic spasms within the first 3 months of life that can be generalized or lateralized, independent of the sleep cycle, and that can occur hundreds of times per day, leading to psychomotor impairment and death.
• Episodic ataxia type 1 (EA1) is a frequent form of hereditary episodic ataxia characterized by brief episodes of ataxia, neuromyotonia, and continuous interictal myokymia. The estimated prevalence of EA2 is approximately 1:500,000.
• Hereditary continuous muscle fiber activity is a rare, non-dystrophic myopathy characterized by generalized myokymia and increased muscle tone associated with delayed motor milestones, leg stiffness, spastic gait, hyperreflexia and Babinski sign. Symptoms may be worsened by febrile illness or anesthesia.
• Isolated autosomal dominant hypomagnesemia, Glaudemans type (IADHG) is a form of familial primary hypomagnesemia characterized by low serum magnesium (Mg) values but normal urinary Mg values. The typical clinical features are recurrent muscle cramps, episodes of tetany, tremor, and muscle weakness, especially in distal limbs. The disease is potentially fatal.
• Paroxysmal kinesigenic dyskinesia (PKD) is a form of paroxysmal dyskinesia, characterized by recurrent brief involuntary hyperkinesia’s, such as choreoathetosis, ballism, athetosis or dystonia, triggered by sudden movements.
Inheritance
KCNA1 is inherited in an autosomal dominant manner. However, an autosomal recessive mode of inheritance for a pathogenic loss-of-function homozygous variant (p.Val368Leu) has been recently reported.
KCNA1