Clinical Guidance

A study of 90 individuals with AOA2 found that pathogenic missense variants in the helicase domain caused less severe AOA2 phenotypes than missense variants outside of this domain, or deletions, or truncating variants of SETX. However, individuals with pathogenic truncating or missense variants outside of the helicase domain had a lower frequency of pyramidal signs – a finding that may reflect masking of the pyramidal signs by severe motor neuropathy .

Source: GeneReviews — "Ataxia with Oculomotor Apraxia Type 2"

Diagnostic Criteria

Suggestive Findings

Ataxia with oculomotor apraxia type 2 (AOA2) should be suspected in individuals with the following clinical, laboratory, and radiographic features.

Clinical features

• Cerebellar ataxia

• Absent or diminished tendon reflexes and later a peripheral axonal sensorimotor neuropathy (90% of individuals)

• Oculomotor apraxia (~51% of individuals)

• Pyramidal signs (Plantar response is either flexor or neutral.)

• Dystonic posture of the hands, choreic movements, head or postural tremor

• Onset between age three and 30 years

• Slow progression

• Absence of cardiac involvement, cancer predisposition, and immunodeficiency; rare or absent telangiectasia

• Absence of severe intellectual disability/ cognitive regression

• Family history consistent with autosomal recessive inheritance

Laboratory features

Source: GeneReviews — "Ataxia with Oculomotor Apraxia Type 2"

Differential Diagnosis

Childhood. The diagnosis of ataxia with oculomotor apraxia type 2 (AOA2) can be difficult to establish in young children because not all features of the disease are present or apparent. AOA2 in childhood needs to be distinguished from the following disorders:

Source: GeneReviews — "Ataxia with Oculomotor Apraxia Type 2"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with oculomotor apraxia type 2 (AOA2), the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended:

• Neurologic examination including assessment of cranial nerve function, gait and limb ataxia, coordination, tone, strength, reflexes, and sensory perception

• Ophthalmologic examination

• Physical therapy and occupational therapy assessment of strength and balance

• Assessment of cognitive function

• Serum cholesterol

• Consultation with a clinical geneticist and/or genetic counselor

• Serum alpha-fetoprotein (AFP) concentration, if not evaluated previously

Treatment of Manifestations

Physical therapy may be helpful, particularly for disabilities resulting from peripheral neuropathy. A wheelchair is usually necessary for mobility by age 30 years. Educational support (e.g., use of a computer with speech recognition and special keyboard for typing) should be provided to compensate for difficulties in reading (caused by oculomotor apraxia) and in writing (caused by upper-limb ataxia).

Prevention of Secondary Complications

A low-cholesterol diet is advised to reduce the risk of adverse health effects of hypercholesterolemia

Surveillance

Routine visits to the attending neurologist are indicated. Ophthalmologic surveillance is recommended. Cholesterol level should be monitored regularly.

Evaluation of Relatives at Risk

See for ...

Source: GeneReviews — "Ataxia with Oculomotor Apraxia Type 2"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Ataxia with Oculomotor Apraxia Type 2"

Surveillance Guidelines

Routine visits to the attending neurologist are indicated. Ophthalmologic surveillance is recommended. Cholesterol level should be monitored regularly.

Source: GeneReviews — "Ataxia with Oculomotor Apraxia Type 2"