TY - JOUR
T1 - Lafora disease in miniature Wirehaired Dachshunds
AU - Swain, Lindsay
AU - Key, Gill
AU - Tauro, Anna
AU - Ahonen, Saija
AU - Wang, Peixiang
AU - Ackerley, Cameron
AU - Minassian, Berge A.
AU - Rusbridge, Clare
N1 - Funding Information:
The Kennel Club Charitable Trust registered charity (No. 327802) partially subsidized the cost of genetic testing of many of the dogs in this study. The Dachshund Breed Council coordinated fundraising to contribute towards the cost of genetic testing. The genetic work was part funded by the Ontario Brain Institute and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (NIH) under award number P01 NS097197. Fitzpatrick Referrals Ltd, provided support in the form of salaries and materials for authors LS, AT and CR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript with the exception of the Dachshund Breed Council which has a Health and Welfare subcommittee which instigated the data collection but did not play a role in analysis. AT and CR are and LS was employed by Fitzpatrick Referrals Ltd, Surrey, GU7 2QQ. CR is also employed by the University of Surrey. SA, PW, CA and BM are employed by the Hospital for Sick Children, University of Toronto. The University of Surrey, The University of Toronto and Fitzpatrick Referrals Ltd did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of authors? salaries and/or research materials. GK is a member of the Lafora disease Subcommittee which is part of the Dachshund Breed Council affiliated with the UK Kennel Club. The Dachshund Breed Council represents the interests of sixteen UK Dachshund Breed Clubs and appoints Health and Welfare Sub-committees to develop policies and coordinate plans for Dachshund breed health improvement. The Lafora disease subcommittee instigated data collection but did not play a role in analysis, decision to publish, preparation of the manuscript or provide financial support other than coordinate fundraising to partially subsidize the cost of genetic testing. None of the authors have personal or financial relationships with other people or organizations that might inappropriately influence or bias the content of the paper. There are no patents, products in development, or marketed products to declare. This does not alter the authors? adherence to PLOS ONE policies on sharing data and materials. The authors are grateful to the Dachshund Breed Council, the Wire Haired Dachshund club and Lafora Subcommittee for enabling this project. In particular we would like to thank Ian Seath, Nora Price, Susan Holt and Roger Sainsbury for their considerable support.
PY - 2017/8
Y1 - 2017/8
N2 - Lafora disease (LD) is an autosomal recessive late onset, progressive myoclonic epilepsy with a high prevalence in the miniature Wirehaired Dachshund. The disease is due to a mutation in the Epm2b gene which results in intracellular accumulation of abnormal glycogen (Lafora bodies). Recent breed-wide testing suggests that the carrier plus affected rate may be as high as 20%. A characteristic feature of the disease is spontaneous and reflex myoclonus; however clinical signs and disease progression are not well described. A survey was submitted to owners of MWHD which were homozygous for Epm2b mutation (breed club testing program) or had late onset reflex myoclonus and clinical diagnosis of LD. There were 27 dogs (11 male; 16 female) for analysis after young mutation-positive dogs that had yet to develop disease were excluded. Average age of onset of clinical signs was 6.94 years (3.5–12). The most common initial presenting sign was reflex and spontaneous myoclonus (77.8%). Other presenting signs included hypnic myoclonus (51.9%) and generalized seizures (40.7%). Less common presenting signs include focal seizures, “jaw smacking”, “fly catching”, “panic attacks”, impaired vision, aggression and urinary incontinence. All these clinical signs may appear, and then increase in frequency and intensity over time. The myoclonus in particular becomes more severe and more refractory to treatment. Signs that developed later in the disease include dementia (51.9%), blindness (48.1%), aggression to people (25.9%) and dogs (33.3%), deafness (29.6%) and fecal (29.6%) and urinary (37.0%) incontinence as a result of loss of house training (disinhibited type behavior). Further prospective study is needed to further characterize the canine disease and to allow more specific therapeutic strategies and to tailor therapy as the disease progresses.
AB - Lafora disease (LD) is an autosomal recessive late onset, progressive myoclonic epilepsy with a high prevalence in the miniature Wirehaired Dachshund. The disease is due to a mutation in the Epm2b gene which results in intracellular accumulation of abnormal glycogen (Lafora bodies). Recent breed-wide testing suggests that the carrier plus affected rate may be as high as 20%. A characteristic feature of the disease is spontaneous and reflex myoclonus; however clinical signs and disease progression are not well described. A survey was submitted to owners of MWHD which were homozygous for Epm2b mutation (breed club testing program) or had late onset reflex myoclonus and clinical diagnosis of LD. There were 27 dogs (11 male; 16 female) for analysis after young mutation-positive dogs that had yet to develop disease were excluded. Average age of onset of clinical signs was 6.94 years (3.5–12). The most common initial presenting sign was reflex and spontaneous myoclonus (77.8%). Other presenting signs included hypnic myoclonus (51.9%) and generalized seizures (40.7%). Less common presenting signs include focal seizures, “jaw smacking”, “fly catching”, “panic attacks”, impaired vision, aggression and urinary incontinence. All these clinical signs may appear, and then increase in frequency and intensity over time. The myoclonus in particular becomes more severe and more refractory to treatment. Signs that developed later in the disease include dementia (51.9%), blindness (48.1%), aggression to people (25.9%) and dogs (33.3%), deafness (29.6%) and fecal (29.6%) and urinary (37.0%) incontinence as a result of loss of house training (disinhibited type behavior). Further prospective study is needed to further characterize the canine disease and to allow more specific therapeutic strategies and to tailor therapy as the disease progresses.
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U2 - 10.1371/journal.pone.0182024
DO - 10.1371/journal.pone.0182024
M3 - Article
C2 - 28767715
AN - SCOPUS:85026628885
VL - 12
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 8
M1 - e0182024
ER -