OMIM ID:
Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating Leukodystrophy
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Reported ocular signs are limited to abnormal eye movements. In other forms of spastic ataxia, nystagmus is evident in association with optic atrophy but no fundus examinations are reported in the 3 families with SPAX8. Hypometric saccades and limited upgaze have also been found in these families.
Systemic Features
First signs and symptoms occur sometime in the first 5 years of life and often in the first year. In 6 of 7 reported patients the presenting sign was nystagmus but one individual with reported onset of disease at age 5 years presented with ataxia. Cerebellar signs, both truncal and limb, are usually present and the majority of individuals have evidence of dystonia. Likewise, pyramidal signs are nearly always present. Cerebellar dysarthria and titubation are often present with dystonic posturing and torticollis.
Brain MRIs usually reveal cerebellar atrophy and widespread hypomyelination. Two individuals in a single family had severe global psychomotor delays as well. No sensory deficits were reported. This disorder is progressive and patients in adulthood may require the use of a wheelchair.
Genetics
Inheritance
Homozygous mutations in the NKX6-2 (NKX6-2) gene (10q26.3) are responsible for this disorder.
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.