OMIM ID:
Ataxia with Oculomotor Apraxia 2
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Patients with this disorder have difficulty initiating voluntary ocular movements upon command or following targets (oculomotor apraxia). This feature is not as prominent or frequent in AOA2 (56%) as it is in ataxia with oculomotor apraxia 1 (208920). Gaze changes are often initiated first by head thrusting, followed by saccadic eye movements. One may test for this by holding the head whereupon the patient is unable to move the eyes. Strabismus and nystagmus are present in a significant proportion of patients. Optokinetic nystagmus is impaired.
Systemic Features
Initial development proceeds normally but cerebellar ataxia with significant gait problems appear toward the end of the first decade of life and sometimes not until the third decade (mean age of onset 15 years). Distal muscle weakness and atrophy are often seen. Mental decline has been observed in a few individuals but does not occur until midlife. Sensorimotor deficits are present in many patients. Tremors, dystonia, and choreiform movements are sometimes seen. Many patients become wheelchair-bound by the 4th decade of life.
Cerebellar atrophy is revealed by MRI. Serum alpha-fetoprotein concentrations are usually elevated while serum creatine kinase is increased in some patients. Circulating cholesterol may also be above normal. Mild serum changes in these components may be seen in heterozygotes. Hypoalbuminemia is not present in AOA2.
Genetics
Inheritance
Homozygous mutations in SETX (9q34.13) are responsible for this disorder. Ataxia with oculomotor apraxia 2 is distinguished from ataxia-telangiectasia (208900) by the lack of telangiectases and immunological deficiencies. It differs from ataxia with oculomotor apraxia 1 (208920) in having a somewhat later onset, somewhat slower course, and milder oculopraxic manifestations. Cogan-type oculomotor apraxia (257550) lacks other neurologic signs. Oculomotor apraxia may be the presenting sign in Gaucher disease (230800, 230900, 231000).
See also Ataxia with Oculomotor Apraxia 3 (615217), and Ataxia with Oculomotor Apraxia 4 (616267).
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.