Hereditary spastic ataxia comprises a heterogeneous group of progressive neurodegenerative disorders characterized by lower-limb spasticity and generalized ataxia with dysarthria, impaired ocular movements, and gait disturbance. Spastic ataxia-1 (SPAX1) is an autosomal dominant form of the disorder with ... Hereditary spastic ataxia comprises a heterogeneous group of progressive neurodegenerative disorders characterized by lower-limb spasticity and generalized ataxia with dysarthria, impaired ocular movements, and gait disturbance. Spastic ataxia-1 (SPAX1) is an autosomal dominant form of the disorder with linkage to chromosome 12p13 (summary by Meijer et al. (2002)). - Genetic Heterogeneity of Spastic Ataxia See also SPAX2 (611302), which maps to chromosome 17p13; SPAX3 (611390), which maps to chromosome 2q33-q34; SPAX4 (613672), caused by mutation in the MTPAP gene (613669) on chromosome 10p11; SPAX5 (614487), caused by mutation in the AFG3L2 gene (604581) on chromosome 18p11; SPAX6 (270550), caused by mutation in the SACS (604490) on chromosome 13q12.12; and SPAX7 (108650).
Mahloudji (1963) described a rare hereditary syndrome of spastic ataxia, closely resembling disseminated sclerosis (126200), in 18 persons in an Iranian family. The pedigree, covering 5 generations, strongly suggests autosomal dominant transmission. It appears to be the same ... Mahloudji (1963) described a rare hereditary syndrome of spastic ataxia, closely resembling disseminated sclerosis (126200), in 18 persons in an Iranian family. The pedigree, covering 5 generations, strongly suggests autosomal dominant transmission. It appears to be the same disorder as was reported by Ferguson and Critchley (1929). Gayle and Williams (1933) described 17 cases in 4 generations of a disorder beginning in the sixth decade with stiffness in the leg muscles, followed by stumbling, dysarthria, and loss of memory. Although progression to severe spastic paraplegia occurred, the disorder did not shorten life. These patients lived in Accomac and Northampton counties on the eastern shore of Virginia. Meijer et al. (2002) described 3 large Newfoundland families with autosomal dominant hereditary spastic ataxia in which most affected individuals initially presented with progressive leg spasticity of variable degrees followed by ataxia in the form of involuntary head jerk, dysarthria, dysphagia, and ocular movement abnormalities with no signs of amyotrophy. The lower limbs showed hyperreflexia and hypertonicity. The ocular movement abnormalities included slow saccades, impaired vertical gaze, and, in some cases, lid retraction. A few patients had additional features, such as dystonia, pes cavus, mild ptosis, and decreased vibration sense in the lower limbs. This phenotype resembled that observed in autosomal recessive Charlevoix-Saguenay spastic ataxia (ARSACS; 270550); however, these families were from a different population and showed a clear pattern of dominant inheritance with a later age at onset than is seen in ARSACS. The severity of the phenotype in the 3 families studied by Meijer et al. (2002) varied greatly within and among the families, and the age at onset was from early childhood to early twenties, although most presented with onset of symptoms at age 10 to 20 years. Neuropathologic findings included degeneration of the corticospinal tracts and posterior columns. The life span and cognition of patients was not affected. There was no recognized kinship between these 3 families, although the detection of a shared disease haplotype suggested that they originated from a common ancestor. In further studies of the 3 large families reported by Meijer et al. (2002) from a historically isolated cluster of rural communities, Grewal et al. (2004) assumed that the affected individuals had the same condition, although they were apparently unrelated. They noted that significant mobility problems were present by the fourth decade, with a broad-based ataxic and spastic gait. MRI scans of the brain and spinal cord were normal. Neuropathologic changes included midbrain neuronal loss. Variability of phenotypic expression could be observed even within the same sibship. Pedigree analysis showed no evidence of anticipation or any sex differences in severity. The condition was unusually prevalent in the province of Newfoundland, which is a characteristic of a founder effect followed by isolation and large family size.