923
Journal of Alzheimer’s Disease 48 (2015) 923–926 DOI 10.3233/JAD-150477 IOS Press
Short Communication
A Novel MAPT Mutation Causing Corticobasal Syndrome Led by Progressive Apraxia of Speech Charles R. Marshalla , Rita Guerreirob , Steffi Thustc , Phillip Fletchera , Jonathan D. Rohrera and Nick C. Foxa,∗ a Dementia
Research Centre, Department of Neurodegenerative Disease, London, UK of Molecular Neuroscience, UCL Institute of Neurology, London, UK c Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, UK b Department
Accepted 14 July 2015
Abstract. The authors describe a case of corticobasal syndrome led by progressive apraxia of speech, associated with a novel mutation in exon 10 of the MAPT gene. Genetic bases for progressive apraxia of speech and corticobasal syndrome are only rarely described, and have not been described in conjunction. Keywords: Corticobasal syndrome, frontotemporal dementia, microtubule-associated protein tau, progressive apraxia of speech
CASE REPORT A 47-year-old right-handed woman presented with progressive speech difficulty. She exhibited apraxia of speech, with associated orofacial apraxia and dysphagia, but with preserved comprehension, and no evidence of agrammatism when using a computer to communicate. Four years after initial symptom onset, she began to experience stiffness and pain of her right arm, with clinical evidence of spasticity, dyspraxia, and dystonia in the affected arm. Examination of her other limbs was unremarkable, and she had no evidence of wasting, fasciculations, or weakness. Her extraocular movements were normal. Six years after initial symptom onset, she had become almost completely mute. ∗ Correspondence
to: Prof. Nick Fox, MD, Dementia Research Centre, Institute of Neurology, Queen Square, London WC1N 3BG, UK. Tel.: +44 0845 155 5000; E-mail: [email protected].
She had no relevant past medical history. Her mother had developed progressive speech difficulty from age 60, and died at age 67 having received a diagnosis of motor neuron disease (MND). She had had some difficulty holding a pen during the course of her illness, but no limb weakness or gait abnormalities were recalled by the family. Her maternal grandparents both died in their 60 s without evidence of neurological disease. She had 5 siblings aged between 48 and 55, and 2 children aged 19 and 23, all of whom were well. There was no history of neurological disease in her father’s family. Neuropsychological evaluation revealed severe speech output impairment, cognitive slowing, and executive dysfunction. Memory, naming, perceptual, and spatial skills were intact. A summary of neuropsychological tests is shown in Table 1. Neurophysiological investigation showed occasional fibrillations and fasciculation potentials in the right first dorsal interosseous muscle, but there was otherwise no evidence of widespread denervation or motor
ISSN 1387-2877/15/$35.00 © 2015 – IOS Press and the authors. All rights reserved
924
C.R. Marshall et al. / Novel MAPT Mutation
Table 1 Summary of neuropsychological test scores (WAIS, Weschler Adult Intelligence Scale; VOSP, Visual Object and Space Perception battery) WAIS-III Verbal IQ WAIS-III Performance IQ WAIS-III subtests Digit Span Vocabulary Similarities Picture Completion Block Design Picture Arrangement Recognition Memory Test for Words (short version) Recognition Memory Test for Faces (short version) Camden Paired Associate Learning Test Graded Naming Test VOSP Object Decision VOSP Cube Analysis Trail Making Test Part B Counting B’s
and in silico analysis predicts an increase in splicing of exon 10, suggesting that the variant is likely to be pathogenic.
88 80
DISCUSSION Borderline (70–79) Low Average (80–89) Average (90–109) Low Average (80–89) Low Average (80–89) Borderline (70–79) >75th %ile 25th–50th %ile 90th %ile 75th–90th %ile >5% cut off >5% cut off
Journal of Alzheimer’s Disease 48 (2015) 923–926 DOI 10.3233/JAD-150477 IOS Press
Short Communication
A Novel MAPT Mutation Causing Corticobasal Syndrome Led by Progressive Apraxia of Speech Charles R. Marshalla , Rita Guerreirob , Steffi Thustc , Phillip Fletchera , Jonathan D. Rohrera and Nick C. Foxa,∗ a Dementia
Research Centre, Department of Neurodegenerative Disease, London, UK of Molecular Neuroscience, UCL Institute of Neurology, London, UK c Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, UK b Department
Accepted 14 July 2015
Abstract. The authors describe a case of corticobasal syndrome led by progressive apraxia of speech, associated with a novel mutation in exon 10 of the MAPT gene. Genetic bases for progressive apraxia of speech and corticobasal syndrome are only rarely described, and have not been described in conjunction. Keywords: Corticobasal syndrome, frontotemporal dementia, microtubule-associated protein tau, progressive apraxia of speech
CASE REPORT A 47-year-old right-handed woman presented with progressive speech difficulty. She exhibited apraxia of speech, with associated orofacial apraxia and dysphagia, but with preserved comprehension, and no evidence of agrammatism when using a computer to communicate. Four years after initial symptom onset, she began to experience stiffness and pain of her right arm, with clinical evidence of spasticity, dyspraxia, and dystonia in the affected arm. Examination of her other limbs was unremarkable, and she had no evidence of wasting, fasciculations, or weakness. Her extraocular movements were normal. Six years after initial symptom onset, she had become almost completely mute. ∗ Correspondence
to: Prof. Nick Fox, MD, Dementia Research Centre, Institute of Neurology, Queen Square, London WC1N 3BG, UK. Tel.: +44 0845 155 5000; E-mail: [email protected].
She had no relevant past medical history. Her mother had developed progressive speech difficulty from age 60, and died at age 67 having received a diagnosis of motor neuron disease (MND). She had had some difficulty holding a pen during the course of her illness, but no limb weakness or gait abnormalities were recalled by the family. Her maternal grandparents both died in their 60 s without evidence of neurological disease. She had 5 siblings aged between 48 and 55, and 2 children aged 19 and 23, all of whom were well. There was no history of neurological disease in her father’s family. Neuropsychological evaluation revealed severe speech output impairment, cognitive slowing, and executive dysfunction. Memory, naming, perceptual, and spatial skills were intact. A summary of neuropsychological tests is shown in Table 1. Neurophysiological investigation showed occasional fibrillations and fasciculation potentials in the right first dorsal interosseous muscle, but there was otherwise no evidence of widespread denervation or motor
ISSN 1387-2877/15/$35.00 © 2015 – IOS Press and the authors. All rights reserved
924
C.R. Marshall et al. / Novel MAPT Mutation
Table 1 Summary of neuropsychological test scores (WAIS, Weschler Adult Intelligence Scale; VOSP, Visual Object and Space Perception battery) WAIS-III Verbal IQ WAIS-III Performance IQ WAIS-III subtests Digit Span Vocabulary Similarities Picture Completion Block Design Picture Arrangement Recognition Memory Test for Words (short version) Recognition Memory Test for Faces (short version) Camden Paired Associate Learning Test Graded Naming Test VOSP Object Decision VOSP Cube Analysis Trail Making Test Part B Counting B’s
and in silico analysis predicts an increase in splicing of exon 10, suggesting that the variant is likely to be pathogenic.
88 80
DISCUSSION Borderline (70–79) Low Average (80–89) Average (90–109) Low Average (80–89) Low Average (80–89) Borderline (70–79) >75th %ile 25th–50th %ile 90th %ile 75th–90th %ile >5% cut off >5% cut off
