An autosomal dominant disorder with episodic ataxia, vertigo, and tinnitus

Abstract

The authors report an autosomal dominant episodic ataxia that is clinically distinct from the other episodic ataxias. Vestibular ataxia, vertigo, tinnitus, and interictal myokymia are prominent; attacks are diminished by acetazolamide. Linkage analyses of markers flanking the EA1 and EA2 loci demonstrate genetic exclusion from the other autosomal dominant episodic ataxias. The authors suggest EA3 for periodic vestibulocerebellar ataxia and EA4 for the disorder described here.

CACNA1A haploinsufficiency causes cognitive impairment, autism and epileptic encephalopathy with mild cerebellar symptoms

“…Targeted sequencing of the CACNA1A gene in all three children revealed a variant in exon 23; c.3832C4T (p.(Arg1278Ter; NM_001127221.1; NG_011569.1; rs121909323)) leading to a premature stop codon and previously associated with EA2. 12,13 Additional sequencing of 35 known epileptic encephalopathy genes in patient 4.1 as described by Michaud et al, 14 was performed and was negative.…”

Pearls & Oy-sters: Episodic ataxia type 2

“…3 It is clinically differentiated from other episodic ataxias through a variety of features including age at onset, spell duration, interictal nystagmus, and genetic locus (table 2). 2,4,5 Genetically, the disorder has been linked to CACNA1A, which encodes the pore-forming subunit of the P/Q-type voltage-gated calcium channel. 1 The P/Q channel is expressed throughout the CNS, but is most densely expressed in cerebellar Purkinje cells and granule layer neurons.…”

Unique disease heritage of the Dutch‐German Mennonite population

“…Recently a fourth disorder, a suggested episodic ataxia 3 (EA3), was reported in a Mennonite kindred [Steckley et al, 2001;Cader et al, 2005]. Individuals presented complaining of several episodes of generalized ataxia, vertigo, uncoordination and imbalance along with other associated disorders such as tinnitus and visual disturbances.…”