Ataxia-Oculomotor Apraxia Syndrome

Abstract

Ataxia-oculomotor apraxia is a distinct entity first comprehensively described in 1988. The features include early childhood onset of ataxia and oculomotor apraxia, mimicking ataxia telangiectasia but without the extraneurologic findings of ataxia telangiectasia. We add to the clinical description of the ataxia-oculomotor apraxia syndrome by reporting eight patients, ages 2 to 15 years, from four families, suggesting autosomal recessive inheritance, with the longest follow-up over 6 years. After initial gait deterioration, all had a nonprogressive course. We have postulated that ataxia-oculomotor apraxia should be established as a separate disease from ataxia telangiectasia or its variants not only by clinical history, examination findings, and course, but primarily by the biologic markers of normal chromosome breakage and radiation sensitivity studies. We found no increased chromosome breakage in the four patients studied and intermediate sensitivity to chronic ionizing radiation of cultured skin fibroblasts on the three patients studied. Family studies revealed an intermediate radiosensitivity from two patients, their asymptomatic parents, and a sister. The lack of chromosome breakage strongly separates ataxia-oculomotor apraxia from ataxia telangiectasia. The radiation sensitivity studies are compatible with two possibilities: (1) symptomatic ataxia telangiectasia heterozygotes, but this would be highly unusual because the degree of clinical involvement in the ataxia-oculomotor apraxia patients is not mild, as would be expected if they were heterozygotes and (2) a separable disease entity, which is the interpretation we favor.

Recessive Ataxia With Ocular Apraxia

“…Comparing the present series with the previous description by Aicardi et al, 7 we found a great constancy and prominence of the peripheral neuropathy and existence of cerebellar atrophy in all patients. Our data also gave an overview of the natural course of AOA that is in disagreement with the findings of Gascon et al, 13 who found a nonprogressive course after initial gait deterioration. Autosomal recessive ataxia with ocular apraxia is a progressive condition allowing, in any case, very long survivals until late adulthood.…”

“…This new form of recessive ataxia was considered rare, and few reports were published thereafter. 13,14 Through a systematic population survey of inherited ataxias we are performing in Portugal, 15 several new families with ataxia associated with ocular apraxia (AOA) have been identified. We decided therefore to study the clinical presentation of this peculiar disease and to define diagnostic criteria.…”

Autosomal Recessive Cerebellar Ataxia with Oculomotor Apraxia (Ataxia-Telangiectasia–Like Syndrome) Is Linked to Chromosome 9q34

“…Results of computed tomography (CT) were normal in six patients and revealed mild cerebellar vermis atrophy in three. Three additional patients, from two consanguineous families, were reported with AOA that presented in early childhood (Hannan et al 1994;Gascon et al 1995). Again, detailed investigations of sensitivity to acute and chronic ionizing radiation did not reveal abnormalities typical of AT.…”

“…Again, detailed investigations of sensitivity to acute and chronic ionizing radiation did not reveal abnormalities typical of AT. On the basis of lack of laboratory evidence for chromosomal instability, it was suggested that AOA was a neurological and genetic entity separate from AT (Aicardi et al 1988;Hannan et al 1994;Gascon et al 1995). However, the families reported were too small to permit linkage analysis, and there has been little progress in determining the genetic basis of AOA/ATL.…”

Clinical and Molecular Characterization of Ataxia with Oculomotor Apraxia Patients In Saudi Arabia

“…Ataxia with Oculomotor Apraxia (AOA) is an autosomal recessive cerebellar ataxia (ARCA) mainly characterized by ataxia, oculomotor apraxia and choeroathetosis [1]. Two clinically overlapping forms were characterized; AOA1 (MIM# 208920) and AOA2 (MIM# 606002).…”