13q syndrome and evidence of linkage to chromosome ataxia: Clinical description of a new episodic Episodic vertical oscillopsia with progressive gait

We describe four families with late onset episodic vertical oscillopsia and progressive gait ataxia. Probands presented between the ages of 40 and 64 with initial symptoms of episodic vertical oscillopsia and interictal downbeat nystagmus. A mild gait ataxia developed over several years. Triggers included physical exertion, alcohol and caffeine. Patients did not respond to acetazolamide. Genetic screening for episodic ataxia types 1 and 2, SCA 1, 2, 3 and 6 were negative. Using ancestral IBD analysis and dense SNP genotyping throughout the genome, an interval of 28.6cM (~14.2Mb) on chromosome 13q12.11q13.3 composed of 1259 SNPs, was shared between affected individuals in two of the four families and highlighted a region of suggestive linkage (LOD > 2.7). Introduction: Oscillopsia is a visual illusion of movement caused by a mismatch in either the gain or the timing of eye movement versus head movement. Patients describe seeing the world “oscillate,” “bounce,” or “shake.” Oscillopsia can be caused by inadequate compensation of eye movement for head movement, inadequate suppression of the vestibulo-ocular reflex (VOR) or by adventitious eye movements. Oscillopsia secondary to cerebellar dysfunction is usually associated with downbeat nystagmus and involves dysfunction of the gaze holding pathways, particularly the flocculonodular lobe. Episodic oscillopsia has been described in patients with Arnold Chiari malformations, bilateral superior canal dehiscence, and Tullio phenomenon. A family with positional downbeat nystagmus with episodic vertical oscillopsia was described by Kattah and Gujrati. Three additional probands who experienced late onset episodic vertical oscillopsia with interictal downbeat nystagmus and a slowly progressive gait ataxia were identified in our database and their clinical features are described here. We used Affymetrix 250K Nsp1 SNP arrays and a novel ancestral identity-by-descent (IBD) mapping technique to identify a single haplotype of 28.6cM (14.2 Mb) on Chromosome 13 shared between two of the 4 families, suggesting a potential interval of linkage. This case series adds to the differential diagnosis of episodic vertical oscillopsia. Case Material: Family 50: A 71 year old woman presented at the age of 62 with a 6 year history of intermittent vertical oscillopsia and progressive gait imbalance. Her spells were triggered by heat, fatigue and emotional stress and would last 15-20 minutes. Interictal examination revealed primary position downbeat nystagmus with gaze-evoked and rebound nystagmus. Saccade accuracy was normal but smooth pursuit was impaired. Limb coordination was normal. Gait was wide-based; the patient was unable to tandem walk. Episodes were not reduced with 250mg bid of acetazolamide. The patient’s mother and maternal aunt developed gait problems in their 50-60’s (Table 1). on 25 May 2007 jnnp.bmj.com Downloaded from