Clinical and molecular findings of ataxia with oculomotor apraxia type 2 in 4 families.

BACKGROUND

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease caused by SETX mutations in 9q34 resulting in cerebellar ataxia in association with peripheral neuropathy, cerebellar atrophy on imaging, an elevated alpha-fetoprotein (AFP) serum level, and occasional oculomotor apraxia.

OBJECTIVE

To describe the clinical and molecular findings of 7 patients with a clinical presentation of AOA2 and their relatives.

DESIGN

Case report.

SETTING

Projet Hospitalier de Recherche Clinique.

PATIENTS

Seven patients with AOA2 and their family members.

INTERVENTION

Linkage analysis and direct sequencing of all exons of SETX were performed in all patients. Magnetic resonance imaging and electroneuromyography were performed and the patients' AFP serum levels were tested.

RESULTS

We identified 7 patients with AOA2 from 4 unrelated families. Three novel SETX mutations were found. The clinical picture of the patients reported is fairly homogeneous and in accordance with the classic AOA2 presentation: onset from 13 to 18 years of progressive cerebellar ataxia and areflexia. Oculomotor apraxia was detected in 1 patient. Predominant axonal neuropathy and a diffuse cerebellar atrophy were found in the 4 patients tested. All patients had elevated AFP serum levels and 5 of 8 nonsymptomatic heterozygous relatives had moderately increased AFP serum levels as well.

CONCLUSIONS

Ataxia with oculomotor apraxia type 2 is a homogeneous form of cerebellar ataxia with occasional oculomotor apraxia. Most nonsymptomatic heterozygous carriers present with increased AFP serum levels.