A 22‐year‐old man is the third of four siblings from a family with a high degree of consanguinity. At 18 months, he was first noted to be unsteady and subsequently developed a slurred speech. His symptoms deteriorated, and at the age of five, he was a wheelchair user. He then developed abnormal posturing of the limbs, as well as a more fidgety appearance and cognitive decline. His older sister was similarly affected and had additional scoliosis, and his younger sister manifested a pigeon‐toed walk at the age of eight.
Upon examination, the patient showed cerebellar ataxia with limb dysmetria and dysarthria (Supporting Video 1). Additionally, he had generalized chorea and dystonia. Oculomotor abnormalities included exotropia and nystagmus. However, the most striking feature was profound oculomotor apraxia. When attempting to look to the side, he used large head thrusts that overshot the target, with eyes in contraversion. When the head adjusts to the target, the eyes lag behind and follow only slowly (oculocephalic dissociation). This pattern was not only observed with volitional or directed saccades, but even with smooth pursuit. The intrusion of square wave jerks disrupted fixation; there was also gaze‐evoked nystagmus. In contrast, in the vertical plane, the abnormalities were limited to broken pursuit, nystagmus, and hypermetric saccades. Additional features not shown on the video were distal wasting, reflex loss, and loss of sensation.
In summary, this man presented with the core features of cerebellar ataxia with oculomotor apraxia. A previously performed MRI showed pancerebellar atrophy. Genetic testing demonstrated a homozygous deletion c.418del, p.(Arg140fs) in aprataxin (APTX), the gene underlying ataxia with oculomotor apraxia type 1 (AOA1). This variant has not been previously described in the literature. The deletion is predicted to result in a frameshift, and therefore lead to premature termination of translation, an underlying mechanism also previously reported in ATPX mutations. Our patient showed a fairly typical presentation of AOA1, with childhood onset of a cerebellar syndrome combined with neuropathy, dystonia, chorea, and intellectual disability.1 Albeit eponymous, oculomotor apraxia is not an obligate feature of the disease, but does correlate with clinical severity. Indeed, although the term oculomotor “apraxia” was used by Cogan 19522 to describe the inability to volitionally initiate saccades (contrasting that they could be initiated by other means), it is not an apraxia, but a cerebellar dysfunction of saccade initiation,3 possibly resulting from posterior vermian atrophy.4 Patients often use eye blinking to de‐fixate, and the head thrusts to direct their eyes to the target, as demonstrated in the video. In severe cases like our patient's, long latency and hypometria of saccades result in dissociation of head and eye movements.
Author Roles
1. Research project: A. Conception, B. Organization, C. Execution; 2. Statistical Analysis: A. Design, B. Execution, C. Review and Critique; 3. Manuscript Preparation: A. Writing of the first draft, B. Review and Critique.
B.B.: 3A
V.R.: 3B
A.L.: 3B
K.B.: 3B
Disclosures
Ethical Compliance Statement: We hereby confirm that the present study conforms to the ethical standards and guidelines of the journal. The authors confirm that the approval of an institutional review board was not required for this work. The patients have given written and informed consent for online publication of their videos.
Funding Sources and Conflicts of Interest: No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work.
Financial Disclosures for previous 12 months: B.B. is supported by the Robert Bosch Foundation. V.R. and A.L. report no disclosures. K.P.B. has received grant support from Welcome/MRC, NIHR, Parkinsons's UK and EU Horizon 2020. He receives royalties from publication of the Oxford Specialist Handbook Parkinson's Disease and Other Movement Disorders (Oxford University Press, 2008), of Marsden's Book of Movement Disorders (Oxford University Press, 2012), and of Case Studies in Movement Disorders–Common and Uncommon Presentations (Cambridge University Press, 2017). He has received honoraria/personal compensation for participating as consultant/scientific board member from Ipsen, Allergan, and Merz; and honoraria for speaking at meetings and from Allergan, Ipsen, Merz, Sun Pharma, Teva, UCB Pharmaceuticals, the American Academy of Neurology, and the International Parkinson's Disease and Movement Disorders Society.
Supporting information
Supporting Video 1: The patient is wheelchair‐bound. There is generalized dystonia with a mild truncal tilt, shoulder elevation on the right, and dystonic hand posturing with overflow dystonia on finger tapping. There is also generalized chorea. He has cerebellar ataxia with dysarthria and limb dysmetria (shown at the end of the video). Oculomotor examination reveals exotropia and profound saccadic initiation difficulties (“oculomotor apraxia”). When attempting to look to the side, he uses large head thrusts that overshoot the target with his eyes in contraversion. After the head is on target, the eyes lag behind and follow only slowly (oculocephalic dissociation). This pattern is not only observed with volitional or directed saccades, but even with smooth pursuit. Fixation is disrupted by intrusion of square wave and there is gaze‐evoked nystagmus. In contrast, in the vertical plane, the abnormalities are limited to broken pursuit, nystagmus, and hypermetric saccades.
Relevant disclosures and conflicts of interest are listed at the end of this article.
References
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Associated Data
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Supplementary Materials
Supporting Video 1: The patient is wheelchair‐bound. There is generalized dystonia with a mild truncal tilt, shoulder elevation on the right, and dystonic hand posturing with overflow dystonia on finger tapping. There is also generalized chorea. He has cerebellar ataxia with dysarthria and limb dysmetria (shown at the end of the video). Oculomotor examination reveals exotropia and profound saccadic initiation difficulties (“oculomotor apraxia”). When attempting to look to the side, he uses large head thrusts that overshoot the target with his eyes in contraversion. After the head is on target, the eyes lag behind and follow only slowly (oculocephalic dissociation). This pattern is not only observed with volitional or directed saccades, but even with smooth pursuit. Fixation is disrupted by intrusion of square wave and there is gaze‐evoked nystagmus. In contrast, in the vertical plane, the abnormalities are limited to broken pursuit, nystagmus, and hypermetric saccades.