OMIM ID:
Ataxia with Oculomotor Apraxia 3
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Ocular movement abnormalities are noted at the same time as other peripheral motor difficulties. Slow saccadic eye movements, and head-eye lag are evident. Pursuit movements are normal.
Systemic Features
Onset of gait instability occurs in the second decade of life with dysmetria and frequent falls. The eye movement abnormalities, dysarthria, and axial dysmetria with distal muscle atrophy and weakness are present at the same time. Distal sensory deficits with lack of sensory nerve action potentials are also present in the lower limbs. The upper limbs are involved somewhat later but with less pronounced movement impairment. Hyporeflexia or areflexia is common. The disorder is progressive with loss of independent mobility by the third decade.
Brain and spinal cord MRI imaging reveals cerebellar atrophy of the folia and vermis. Persistently elevated alpha-fetoprotein levels have been found but no hypoalbuminemia.
Genetics
Inheritance
Homozygous missense mutations in the PIK3R5 gene (17p12-p13) have been associated with this clinical picture in one family of 4 affected sibs born of consanguineous parents.
See also Ataxia with Oculomotor Apraxia 1 (208920) with hypoalbuminemia, Ataxia with Oculomotor Apraxia 2 (606002) (also known as Spinocerebellar Ataxia, Autosomal Recessive 1 or SCAR1), 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.