Myoclonus from selective dentate nucleus degeneration in type 3 Gaucher disease

Objective: To describe a case with a new genetic variant of type 3 Gaucher disease presenting with stimulus-sensitive and action myoclonus in the pres ence of selective dentate abnormalities. Design: Clinical, pathologic, and molecular genetic studies. Setting: Medical school departments. Patient: A B-year-old girl with type 3 Gaucher disease experienced progress ively crippling generalized stimulus-sensitive and action myoclonus. Repeat ed electroencephalographic examination did not show cortical activity assoc iated with the myoclonus, suggesting its subcortical origin. Neuropathologi cal examination revealed selective degeneration of the cerebellar dentate n ucleus and dentatorubrothalamic pathway in the face of essentially complete lack of storage in the brain. Mutation analysis identified the following 2 mutant alleles: one with a V394L mutation and the other with the lesion Re cTL (D409H + L444P + A456P + V460V), which resulted from a recombination ev ent, with the pseudogene located 16 kilobases downstream from the structura l gene. Conclusion: Given the restricted abnormalities, this genetically unique cas e provides insight into the pathogenesis of myoclonus and suggests a promin ent role for the cerebellar dentate nucleus in its genesis.