OMIM ID:
Ataxia with Oculomotor Apraxia 1
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Patients with this disorder have difficulty initiating voluntary ocular movements upon command or when following targets (oculomotor apraxia). 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. Ocular apraxia is often evident a few years after symptoms of ataxia are noted and may progress to external ophthalmoplegia. Most patients have exaggerated blinking.
Systemic Features
The ataxia is cerebellar in origin with onset usually in the first decade of life (mean age of onset 4.3 years). It is associated with peripheral axonal neuropathy and hypoalbuminemia. Gait imbalance is usually the first symptom followed by upper limb dysmetria. Other variable signs include dysarthria, choreiform or athetoid movements, facial grimacing, tongue and limb fasciculations, areflexia, and distal sensory deficits. All symptoms are progressive and ambulation is lost within a decade of onset. Cerebellar atrophy may be seen on MRI and the EMG shows evidence of axonal neuropathy. Mental function is normal in most patients but some have cognitive impairments.
Genetics
Inheritance
Mutations in the APTX gene (9p21.1) encoding aprataxin are responsible for this autosomal recessive condition.
There is evidence of clinical and genetic heterogeneity. At least two loci are involved, with the mutation at 9p13 causing an earlier onset of disease (first decade), and hypoalbuminemia, while the second one, ataxia with oculomotor apraxia 2 [606002]) at 9q34 causes a disorder of later onset (2nd or third decade) in which oculomotor apraxia is an inconsistent finding. Oculomotor apraxia is more consistently found in the disorder described here. Cogan-type oculomotor apraxia (257550) lacks other neurologic signs.
See also Ataxia with Oculomotor Apraxia 3 (615217), and Ataxia with Oculomotor Apraxia 4 (616267).
Oculomotor apraxia may be the presenting sign in Gaucher disease (230800, 230900, 231000).
The ocular phenotype is similar to that seen in ataxia-telangiectasia (208900).
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.