OMIM ID:
Spastic Ataxia 6, Charlevoix-Saguenay Type
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Patches of myelinated axons from retinal neurons in the retina are not unusual in the general population but are especially prominent among families in Canada with SPAX6. These typically appear as striated white or yellowish-white patches with ‘fuzzy’ borders in the nerve fiber layer of the retina and radiate from the disc. These findings are usually of no functional significance but if sufficiently large and dense can be demonstrated on perimetry as small scotomas. OCT studies in two Belgian families have revealed increased thickness of the peri-papillary retinal nerve fiber layer in both patients and carriers without clinical evidence of myelination. In addition the retinal nerve fiber layer has been described as 'hypertrophied' outside the areas of myelination. Horizontal gaze nystagmus and deficits in conjugate pursuit movements are often present.
Systemic Features
This neurodegenerative disorder begins in early childhood (12-18 months) with signs of cerebellar ataxia, pyramidal signs, and peripheral neuropathy. Slightly older children develop a mixed-sensorimotor peripheral neuropathy. Dysarthria, limb spasticity, distal muscle wasting, and mitral valve prolapse are often present. Knee reflexes are exaggerated while ankle reflexes are often absent. Extensor plantar responses are usually present. The EMG can show signs of denervation with slowed conduction while brain neuroimaging demonstrates regional atrophy in the cerebellum, especially the superior vermis. Most patients eventually become wheelchair-bound. However, cognitive and daily living skills are preserved into adulthood. Most patients live into the sixth decade.
Genetics
Inheritance
Homozygous or compound heterozygous mutations in the SACS gene (13q12.12) are responsible for this autosomal recessive disorder.
The largest number of cases is found in the Charlevoix-Saguenay region of Quebec, Canada among the descendents of a founder but families have also been found in Asia and Europe.
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.