HEREDITARY DYSPHASIC DISINHIBITION DEMENTIA - A FRONTOTEMPORAL DEMENTIA LINKED TO 17Q21-22

Objective: The clinical and pathologic features of hereditary dysphasi c disinhibition dementia (HDDD) are described to determine whether it is a variant of known dementias. Background: Several dementing disorde rs have clinical and pathologic similarities with AD, Pick's disease, and the ''nonspecific'' dementias. A detailed description of clinical and pathologic presentation will aid classification, but ultimately th e discovery of causative gene(s) will define these disorders. Methods: The authors performed a clinical assessment: gross and microscopic pa thologic evaluation of brain tissue, genetic linkage studies, and sequ ence analyses. Results: HDDD is an autosomal-dominant frontotemporal d ementia with many similarities to Pick's disease. Salient clinical fea tures are global dementia with disproportionate dysphasia and ''fronto temporal'' symptoms. A linkage between HDDD and 17q21-22 was shown, wi th a maximum lod score of 3.68 at zero recombination. Conclusions: Sev eral dementias have been linked to the same region and have been terme d frontotemporal dementia with parkinsonism linked to chromosome 17. T hese disorders may represent phenotypic variants arising from mutation s within a common gene.