Objective: Autosomal dominant cerebellar ataxia with deafness and narcolepsy (ADCA-DN) is an emerging syndrome caused by mutations in the C-terminus end of the TS domain of the DNMT1 gene. ADCA-DN is also associated with sensorimotor polyneuropathy, extrapyramidal, and dysautonomic signs, as well as dementia. Little has been reported about the progressive cognitive impairment associated with ADCA-DN. Our objective is to provide a detailed characterization of the cognitive profile of ADCA-DN. Method: Three members of a kindred with ADCA-DN underwent comprehensive neuropsychological testing and neuroimaging. Results: At baseline, 2 individuals demonstrated cognitive profiles with executive difficulties in some areas consistent with frontalsystem dysfunction behaviorally and on standardized testing. The third individual was further in the disease course and exhibited more globally impaired cognition consistent with a diagnosis of dementia. Conclusions: This family demonstrated progressive neurodegeneration beginning with isolated areas of executive dysfunction and leading to globally impaired cognition and dementia. Cognitive decline occurred in parallel with neurological deterioration. The cognitive profile is similar to case reports of other individuals with an allelic neurological phenotype, Hereditary Sensory Autonomic Neuropathy 1E, also caused by DNMT1 mutations.

Additional Metadata
Keywords ADCA-DN, Cognition, DNMT1, HSAN 1E, Neuropsychology
Persistent URL dx.doi.org/10.1037/neu0000322
Journal Neuropsychology
Citation
Walker, L.A.S, Bourque, P. (Pierre), Smith, A.M. (Andra M.), & Chardon, J.W. (Jodi Warman). (2017). Autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN) associated with progressive cognitive and behavioral deterioration. Neuropsychology, 31(3), 292–303. doi:10.1037/neu0000322