Abstract Details

Title Eye Movement and Lid Disorders in Patients With Alternating Hemiplegia of Childhood due to ATP1A3 Gene Variants

Topic Neuro-ophthalmology/Neuro-otology

Presentation(s) P10 - Poster Session 10 (8:00 AM-9:00 AM)

Poster/Presentation
Number 17-011

Objective N/A

Background ATP1A3 gene pathogenic variants cause heterogeneous neurological phenotypes, including alternating hemiplegia of childhood (AHC), rapid-onset dystonia-parkinsonism (RDP), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome. Paroxysmal neurological episodes—such as hemiplegia, dystonia, ataxia, and seizure-like events— are common; progressive findings include developmental delay and cognitive impairment. Hours-long ocular motor episodes are reported; however, they have not been systematically characterized.

Design/Methods Home videos of 29 abnormal eye movement episodes from 11 AHC patients with pathogenic variants in ATP1A3 were analyzed and categorized.

Results Monocular deviation/strabismus (MD/S) occurred in 34% of episodes (n=7 exo, 2 eso, 1 hyper), conjugate tonic gaze deviation in 31%, and nystagmus in 17% (n=3 downbeat, 1 upbeat, 1 right beat). Lid findings (all co-existing with abnormal eye movements) included ptosis in 31% of episodes and dynamic lid movements (e.g., excess blinking, lid twitches/flutters) in 31%. In the 7 patients with MD/S and exotropia, all exhibited a unique eye movement, consisting of sudden large abduction of one eye accompanied by dissociated nystagmus/saccadic pulses in the abducting eye. Four additional patients had unidirectional horizontal saccadic pulses without prominent ocular misalignment.

Conclusions This study provides detailed analysis of episodic ocular motor and lid abnormalities in ATP1A3-related AHC. The diversity of findings highlights the phenotypic complexity of paroxysms, though most eye movements could be categorized into monocular gaze deviations, conjugate tonic gaze deviations, or classic nystagmus patterns. Several other disorders can also cause paroxysmal conjugate gaze deviations or nystagmus; however, the abrupt onset of monocular abduction accompanied by abducting saccadic pulses is unique, and possibly pathognomonic for AHC. Hypothetical mechanisms for this type of event may include third nerve or medial longitudinal fasciculus hypofunction, sixth nerve activation, or aberrant innervation between the two.

Authors/Disclosures
Abdulaziz Al-Abdulghani, MD PRESENTER	Dr. Al-Abdulghani has nothing to disclose.
Claudio M. De Gusmao, MD	Dr. DeGusmao has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mendelics Genomic Analysis. Dr. DeGusmao has received personal compensation in the range of $0-$499 for serving as a Consultant for EBSCO publishing. Dr. DeGusmao has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Clinical Outcome Solutions. Dr. DeGusmao has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for PTC Therapeuthics. The institution of Dr. DeGusmao has received research support from FDA.
Michael C. Brodsky, MD	Dr. Brodsky has nothing to disclose.
David S. Zee, MD (Johns Hopkins Hospital)	Dr. Zee has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for florida legal. Dr. Zee has received publishing royalties from a publication relating to health care. Dr. Zee has received personal compensation in the range of $500-$4,999 for serving as a lectuer with u of pittsburg physical therapy. Dr. Zee has received personal compensation in the range of $500-$4,999 for serving as a lecturer with johms hopkins CME.
Fernando Kok, MD	No disclosure on file
Matheus A. Castro, MD	Mr. Castro has nothing to disclose.
Ganeshwaran H. Mochida, MD	Dr. Mochida has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MedLink Neurology. The institution of Dr. Mochida has received research support from National Institutes of Health. The institution of Dr. Mochida has received research support from Rare Village Foundation.
Janet C. Rucker, MD	Dr. Rucker has nothing to disclose.

��ɫ��

��ɫ��