OMIM ID:
Spinocerebellar Ataxia 18
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Ocular signs in SCAR18 include nystagmus, oculomotor apraxia, and optic atrophy. The nystagmus may be rotatory or horizontal and can be gaze-evoked. Some patients have intermittent and tonic upgaze. Visual acuity has not been reported.
Systemic Features
Patients are developmentally delayed and have intellectual disability. These features do not seem to be progressive. Ataxia, both truncal and cerebellar, is present. Mobility is impaired from early childhood and eventually requires assistance. Joint contractures sometimes develop and patients can be wheelchair-bound by the second decade. Dysarthric speech is common. No dysmorphic facial features are present.
Brain imaging shows progressive cerebellar and sometimes cerebral atrophy.
Genetics
Inheritance
This autosomal recessive disorder results from homozygous deletions in the GRID2 gene (4q22). This gene codes for a subunit of the glutamate receptor channel and is thought to be selectively expressed in the Purkinje cells of the cerebellum.
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.