Abstract
To investigate cerebellar dysfunctions and quantitatively characterize specific oculomotor changes in ataxia-telangiectasia-like disorder (ATLD), a rare autosomal recessive disease caused by mutations in the MRE11 gene. Additionally, to further elucidate the pathophysiology of cerebellar damage in the ataxia-telangiectasia (AT) spectrum disorders. Saccade dynamics, metrics, and visual fixation deficits were investigated in two Italian adult siblings with genetically confirmed ATLD. Visually guided saccades were compared with those of 40 healthy subjects. Steady fixation was tested in primary and eccentric positions. Quantitative characterization of saccade parameters, saccadic intrusions (SI), and nystagmus was performed. Patients showed abnormally hypermetric and fast horizontal saccades to the left and greater inaccuracy than healthy subjects in all saccadic eye movements. Eye movement abnormalities included slow eye movements that preceded the initial saccade. Horizontal and vertical spontaneous jerk nystagmus, gaze-evoked, and rebound nystagmus were evident. Fixation was interrupted by large square-wave jerk SI and macrosaccadic oscillations. Slow eye movements accompanying saccades, SI, and cerebellar nystagmus are frequently seen in AT patients, additionally our ATLD patients showed the presence of fast and hypermetric saccades suggesting damage of granule cell-parallel fiber-Purkinje cell synapses of the cerebellar vermis. A dual pathogenetic mechanism involving neurodevelopmental and neurodegenerative changes is hypothesized to explain the peculiar phenotype of this disease.
Highlights
Autosomal recessive cerebellar ataxias with DNA-double strand break repair deficits are a group of severe neurodegenerative and systemic diseases featuring early-onset ataxia and radiosensitivity including ataxia-telangiectasia (AT), the most common disorder of this group, and ataxia-telangiectasialike disorder (ATLD) [1]
This study shows fast, hypermetric saccades sometimes preceded by slow eye movements, saccadic intrusions (SI), macrosaccadic oscillations (MSO), and different types of nystagmus
(spontaneous jerk type, gaze-evoked, and rebound nystagmus) in two siblings with ATLD. These results confirm that oculomotor alterations are common to ATLD and AT including slow eye movements, especially following saccades in AT, SI, and different types of cerebellar nystagmus [21,22,23]
Summary
Autosomal recessive cerebellar ataxias with DNA-double strand break repair deficits are a group of severe neurodegenerative and systemic diseases featuring early-onset ataxia and radiosensitivity including ataxia-telangiectasia (AT), the most common disorder of this group, and ataxia-telangiectasialike disorder (ATLD) [1]. ATLD is a very rare autosomal recessive disease due to mutations in the MRE11 gene [2]. The clinical features of the majority of patients with ATLD resemble those of patients with AT including progressive cerebellar ataxia, oculomotor apraxia, and cellular hypersensitivity to ionizing radiations, with a generally mild presentation and slow progression [12]. Clinical descriptions of oculomotor changes in both AT and ATLD patients show inability to initiate voluntary saccades, saccade hypometria, delayed convergence and impaired smooth pursuit, vestibulo-ocular reflex (VOR), and optokinetic nystagmus [7, 10]; fixation abnormalities such as saccadic intrusions (SI), drifts, spontaneous, gaze-evoked, and down-beat nystagmus [7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
