A pathogenic progranulin mutation and C9orf72 repeat expansion in a family with frontotemporal dementia.
Bottom Line: Brain imaging from available cases showed a symmetrical pattern of atrophy particularly affecting the frontal and temporal lobes.Pathologically two cases were classified as FTLD-TDP type A with TDP-43 positive inclusions, with additional p62-positive 'star-like' inclusions found in the hippocampal formation and cerebellum.However the driving force of the pathological process may be either pathogenic mutation or a combination of both converging on a singular mechanism.
Affiliation: Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.Show MeSH
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Mentions: This 62-year-old woman presented with a 3-year history of speech, gait, behavioural and cognitive impairment. Her initial problem was of impaired articulation which steadily deteriorated with subsequent development of an unsteady gait. Over the same time period she had developed a change in her personality, becoming less extrovert than previously and less interested in doing her normal hobbies. In the year before presentation she also developed impairment of her language, spelling and arithmetic skills as well as dysphagia. She had coeliac disease but had been otherwise well previously. On examination her Mini Mental State Examination (MMSE) was 27/30. She had a bulbar dysarthria with decreased palatal elevation and orofacial apraxia. She had mild generalized wasting in the limbs but no fasciculation's. Power was mildly decreased in all muscle groups. Reflexes were brisk throughout with downgoing plantars. She had bilateral dysdiadochokinesis and gait ataxia. Neuropsychometry showed a verbal IQ of 84 and performance IQ of 86. Episodic memory was impaired with difficulties on tasks of naming, spelling, calculation and limb praxis. There was evidence of executive dysfunction but visuoperceptual skills were intact. EMG showed evidence of mild chronic denervation in tibialis anterior bilaterally but was otherwise normal. MRI brain showed relatively symmetrical generalized cortical atrophy with a frontotemporal predominance as well as mild cerebellar atrophy (Figure 2). A diagnosis of probable FTD-MND was made at this time although the features of ataxia were felt to be unusual. She was not seen again and died 4 years later.
Affiliation: Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.