Trudeau et al. (2006) reported a family of Swedish and Norwegian origin with highly variable neurologic deficits. The proband was a 9-year-old boy with markedly delayed psychomotor development, attention deficit disorder, and cerebellar ataxia. Features included ataxic wide-based ... Trudeau et al. (2006) reported a family of Swedish and Norwegian origin with highly variable neurologic deficits. The proband was a 9-year-old boy with markedly delayed psychomotor development, attention deficit disorder, and cerebellar ataxia. Features included ataxic wide-based gait, dysmetria in the upper limbs, and dysarthria, with normal strength, tone, and reflexes. He also had esophoria, amblyopia, and gaze-evoked nystagmus. Brain MRI showed moderate pancerebellar atrophy, accentuated in the vermal and parasagittal regions, as well as optic nerve hypoplasia. There were no cerebral abnormalities. His mother and maternal aunt had a history of emotional instability and mild cognitive impairment, and a first cousin had attention deficit-hyperactivity disorder (ADHD; 143465). A brother of the proband was noted to have impaired cognition and another cousin was noted to have ADHD, but they were not studied at the molecular level. In addition, none of the family members besides the proband was available for formal clinical evaluation or brain imaging studies. The proband was ascertained during a study of 151 patients with ataxia who were screened specifically for mutations in the SCN8A gene (see MOLECULAR GENETICS).
Because SCN8A is widely expressed in neurons of the central and peripheral nervous systems, and because mutations in the mouse ortholog result in ataxia and other movement disorders, Trudeau et al. (2006) screened the 26 coding exons of ... Because SCN8A is widely expressed in neurons of the central and peripheral nervous systems, and because mutations in the mouse ortholog result in ataxia and other movement disorders, Trudeau et al. (2006) screened the 26 coding exons of SCN8A in 151 patients with inherited or sporadic ataxia and no mutations in known ataxia-related genes. They found a heterozygous 2-bp deletion in exon 24 (600702.0001) in a 9-year-old boy with mental retardation, pancerebellar atrophy, and ataxia. Three additional family members who were heterozygous for this mutation exhibited milder cognitive behavioral deficits including ADHD. However, Trudeau et al. (2006) noted that it was unclear whether the relatives of the proband had a milder version of the neurologic abnormalities seen in the proband due to haploinsufficiency for SCN8A, or if the proband's symptoms were caused by an unrelated developmental disorder.