title: Of brain and bone: the unusual case of Dr. A.
abstract: Frontotemporal dementia (FTD) is a clinical syndrome characterized by progressive decline in social conduct and a focal pattern of frontal and temporal lobe damage. Its biological basis is still poorly understood but the focality of the brain degeneration provides a powerful model to study the cognitive and anatomical basis of social cognition. Here, we present Dr. A, a patient with a rare hereditary bone disease (hereditary multiple exostoses) and FTD (pathologically characterized as Pick's disease), who presented with a profound behavioral disturbance characterized by acquired sociopathy. We conducted a detailed genetic, pathological, neuroimaging and cognitive study, including a battery of tests designed to investigate Dr. A's abilities to understand emotional cues and to infer mental states and intentions to others (theory of mind). Dr. A's genetic profile suggests the possibility that a mutation causing hereditary multiple exostoses, Ext2, may play a role in the pattern of neurodegeneration in frontotemporal dementia since knockout mice deficient in the Ext gene family member, Ext1, show severe CNS defects including loss of olfactory bulbs and abnormally small cerebral cortex. Dr. A showed significant impairment in emotion comprehension, second order theory of mind, attribution of intentions, and empathy despite preserved general cognitive abilities. Voxel-based morphometry on structural MRI images showed significant atrophy in the medial and right orbital frontal and anterior temporal regions with sparing of dorsolateral frontal cortex. This case demonstrates that social and emotional dysfunction in FTD can be dissociated from preserved performance on classic executive functioning tasks. The specific pattern of anatomical damage shown by VBM emphasizes the importance of the network including the superior medial frontal gyrus as well as temporal polar areas, in regulation of social cognition and theory of mind. This case provides new evidence regarding the neural basis of social cognition and suggests a possible genetic link between bone disease and FTD.
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA 94143, USA.
authors.forename: J
authors.initials: J
authors.lastname: Narvid
authors.forename: M L
authors.initials: ML
authors.lastname: Gorno-Tempini
authors.forename: A
authors.initials: A
authors.lastname: Slavotinek
authors.forename: S J
authors.initials: SJ
authors.lastname: Dearmond
authors.forename: Y H
authors.initials: YH
authors.lastname: Cha
authors.forename: B L
authors.initials: BL
authors.lastname: Miller
authors.forename: K
authors.initials: K
authors.lastname: Rankin
mesh_terms: D000368:Aged; D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015897:Comorbidity; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004645:Empathy / Q000235:genetics; D005097:Exostoses, Multiple Hereditary / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D017809:Fatal Outcome; D057180:Frontotemporal Dementia / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010375:Pedigree; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012920:Social Behavior Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D056345:Theory of Mind / Q000502:physiology; D000099065:Exostosin 2
chemical_list: D017351:N-Acetylglucosaminyltransferases; D000099065:Exostosin 2