LAUSR

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. 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 1952 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, possibly resulting from posterior vermian atrophy. 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.