Childhood-onset CADASIL: clinical, imaging, and neurocognitive features.
CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a progressive neurodegenerative condition, associated with mutations in the notch3 gene. Symptoms include migraine with aura, mood disorders, progressive cognitive decline, subcortical ischemic strokes, dementia, and premature death. We present an 8-year-old boy with attention and behavioral difficulties, as well as a family history of the condition. Magnetic resonance imaging revealed subcortical foci of increased T2 hyperintensity, and sequencing of the notch3 gene revealed 1 previously reported mutation and 1 novel sequence variant. Neurocognitive assessment revealed deficits in several aspects of executive functioning and in verbal learning. To our knowledge, this is the youngest reported patient with this condition, and it prompts reconsideration of CADASIL as an adult-onset disease.
Hartley
Jessica
J
Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Westmacott
Robyn
R
Decker
Jochen
J
Shroff
Manohar
M
Yoon
Grace
G
D017668:Age of Onset; D001921:Brain / Q000473:pathology*; D046589:CADASIL / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D002648:Child; D003072:Cognition Disorders / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D014644:Genetic Variation; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D009483:Neuropsychological Tests; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics; D017422:Sequence Analysis, DNA
C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch