Clinical Characteristics
Ocular Features
Horizontal nystagmus is present in some patients.
Systemic Features
Cerebellar ataxia, dysarthria, and spasticity of the lower limbs appear in the first two decades of life. The spasticity may involve all 4 limbs late in life. Cognition is not impacted. Cervical dystonia has been noted. No consistent changes have been found on brain imaging. The neurologic signs are slowly progressive although patients may remain ambulatory.
Tremor, clonus, and extrapyramidal chorea has been seen in several families with what has been called spastic paraplegia-58 which may be the same disorder as SPAX2 since mutations are found in the same gene (KIF1C). Symptoms and prognosis are similar in these conditions except for the reported presence of developmental delay and mild mental retardation in some individuals diagnosed to have SPG58.
Genetics
Inheritance
This is an autosomal recessive condition as the result of homozygous mutations in the KIF1C gene (17p13.2).
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.