Episodic ataxia type 1 (EA1) is a potassium channelopathy (CP) characterized by constant myokymia and dramatic episodes of spastic contractions of the skeletal muscles of the head, arms, and legs with loss of both motor coordination and balance. During attacks some individuals may experience vertigo, blurred vision, diplopia, nausea, headache, diaphoresis, clumsiness, stiffening of the body, dysarthric speech, and difficulty in breathing. These episodes may last seconds to minutes, and can be precipitated by anxiety, emotional stress, fatigue, startle response or sudden postural changes (kinesigenic stimulation). Epilepsy is overrepresented in cases of EA1. Other symptoms include delayed motor development, cognitive disability, choreoathetosis, and carpal spasm. EA1 onset is in childhood or early adolescence. It is inherited in an autosomal dominant manner and genetic analysis of several EA1 families has lead to the discovery of a number of point mutations in the voltage-dependent potassium channel gene KCNA1 (Kv1.1), on chromosome 12p13. To date KCNA1 is the only gene known to be associated with EA1. Functional studies have shown that these mutations impair Kv1.1 channel function with variable effects on channel assembly, trafficking and kinetics. Despite solid evidence obtained on the molecular mechanisms underlying EA1, how these cause dysfunctions within the central and peripheral nervous systems circuitries remains for the most part obscure. Without doubt, EA1 research is important for the identification of signaling pathways involved in this disease and also to find novel pharmacological interventions. More broadly, however, this research may serve as a paradigm for studying related disorders, help in the understanding of the functional properties of the proteins involved and shed new light on the physiological workings of the human body.
|Title of host publication||Ataxia|
|Subtitle of host publication||Causes, Symptoms and Treatment|
|Publisher||Nova Science Publishers, Inc.|
|Number of pages||29|
|Publication status||Published - Feb 2012|
ASJC Scopus subject areas