OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is associated with frontotemporal dementia (FTD) in 14% of cases. Five percent report a family history of ALS, and other ALS patients report a family history of other neurodegenerative diseases. The objective of this study was to conduct a family aggregation study of ALS, and neurodegenerative and neuropsychiatric conditions in ALS kindreds and matched healthy controls. The aim was to determine the true rate of familial ALS and the recurrence risk of ALS in family members, and to identify kindreds with increased aggregation of neurodegenerative and neuropsychiatric disease in the context of the recently described expanded hexanucleotide repeat in C9orf72. METHODS: A prospective, population-based, case-control family aggregation study was conducted. Family history information was collected through questionnaires and interviews from ALS patients and matched controls. Cause of death was verified with death certification. The recurrence rate of ALS and the risk in family members of other neurodegenerative and neuropsychiatric disease was calculated using the relative risk (lambda) and cumulative risk using Kaplan-Meier analysis. RESULTS: Medical histories from 9,684 first- and second-degree relatives of 172 ALS probands and 192 controls were obtained. Cause of death was verified in 2,494 cases. Sixteen percent (n=27) of ALS patients had a family history of ALS. The lifetime hazard ratio (HR) of developing ALS among first- and second-degree relatives was 34.3 (p<0.0001) in relatives of ALS patients with the C9orf72 repeat expansion, and 2.3 (p=0.019) in relatives of ALS patients without the expansion. The relatives of ALS patients also had an increased HR of developing a psychotic illness (HR=4.7, p=0.004, 95% confidence interval [CI]=1.6-12.3) and of suicide (HR=5.6, p<0.0001, 95% CI=2.4-12.9) INTERPRETATION: The true rate of familial ALS in Ireland is 16%. There is an overlap between ALS, FTD, and neuropsychiatric disease that is pronounced in kindreds with the C9orf72 repeat expansion, but is also present in kindreds of those without the C9orf72 expanded repeat.
OBJECTIVE:Amyotrophic lateral sclerosis (ALS) is associated with frontotemporal dementia (FTD) in 14% of cases. Five percent report a family history of ALS, and other ALSpatients report a family history of other neurodegenerative diseases. The objective of this study was to conduct a family aggregation study of ALS, and neurodegenerative and neuropsychiatric conditions in ALS kindreds and matched healthy controls. The aim was to determine the true rate of familial ALS and the recurrence risk of ALS in family members, and to identify kindreds with increased aggregation of neurodegenerative and neuropsychiatric disease in the context of the recently described expanded hexanucleotide repeat in C9orf72. METHODS: A prospective, population-based, case-control family aggregation study was conducted. Family history information was collected through questionnaires and interviews from ALSpatients and matched controls. Cause of death was verified with death certification. The recurrence rate of ALS and the risk in family members of other neurodegenerative and neuropsychiatric disease was calculated using the relative risk (lambda) and cumulative risk using Kaplan-Meier analysis. RESULTS: Medical histories from 9,684 first- and second-degree relatives of 172 ALS probands and 192 controls were obtained. Cause of death was verified in 2,494 cases. Sixteen percent (n=27) of ALSpatients had a family history of ALS. The lifetime hazard ratio (HR) of developing ALS among first- and second-degree relatives was 34.3 (p<0.0001) in relatives of ALSpatients with the C9orf72 repeat expansion, and 2.3 (p=0.019) in relatives of ALSpatients without the expansion. The relatives of ALSpatients also had an increased HR of developing a psychotic illness (HR=4.7, p=0.004, 95% confidence interval [CI]=1.6-12.3) and of suicide (HR=5.6, p<0.0001, 95% CI=2.4-12.9) INTERPRETATION: The true rate of familial ALS in Ireland is 16%. There is an overlap between ALS, FTD, and neuropsychiatric disease that is pronounced in kindreds with the C9orf72 repeat expansion, but is also present in kindreds of those without the C9orf72 expanded repeat.
Authors: Mark T W Ebbert; Christian A Ross; Luc J Pregent; Rebecca J Lank; Cheng Zhang; Rebecca B Katzman; Karen Jansen-West; Yuping Song; Edroaldo Lummertz da Rocha; Carla Palmucci; Pamela Desaro; Amelia E Robertson; Ana M Caputo; Dennis W Dickson; Kevin B Boylan; Rosa Rademakers; Tamas Ordog; Hu Li; Veronique V Belzil Journal: Acta Neuropathol Date: 2017-08-14 Impact factor: 17.088
Authors: Kevin F Bieniek; Marka van Blitterswijk; Matthew C Baker; Leonard Petrucelli; Rosa Rademakers; Dennis W Dickson Journal: JAMA Neurol Date: 2014-06 Impact factor: 18.302
Authors: Margaret O'Brien; Tom Burke; Mark Heverin; Alice Vajda; Russell McLaughlin; John Gibbons; Susan Byrne; Marta Pinto-Grau; Marwa Elamin; Niall Pender; Orla Hardiman Journal: JAMA Neurol Date: 2017-12-01 Impact factor: 18.302
Authors: Meinie Seelen; Perry T C van Doormaal; Anne E Visser; Mark H B Huisman; Margot H J Roozekrans; Sonja W de Jong; Anneke J van der Kooi; Marianne de Visser; Nicol C Voermans; Jan H Veldink; Leonard H van den Berg Journal: J Neurol Date: 2014-07-25 Impact factor: 4.849