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 (loss of muscle coordination) characterized by brief episodes of ataxia, neuromyotonia (spontaneous, continuous muscular activity), and continuous interictal myokymia (involuntary muscular movement). 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 and spastic gait. 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 abnormal movements of the body, of different characteristics, triggered by sudden movements.
Inheritance
KCNA1 is inherited in an autosomal dominant manner. Most individuals diagnosed with a KCNA1-associated disorder have an affected parent; however, de novo pathogenic variants have been reported. Each child of an individual with a KCNA1-associated disorder has a 50% chance of inheriting the KCNA1 pathogenic variant.
However, an autosomal recessive mode of inheritance has been recently reported. This means that in some cases, two copies of an abnormal gene must be present for the disease or trait to develop.
KCNA1