[en] Mutations in the FIG4 gene have been identified in various diseases, including amyotrophic lateral sclerosis, Parkinson's disease, and Charcot-Marie-Tooth 4 J (CMT4J), with a wide range of phenotypic manifestations. We present eight cases of CMT4J patients carrying the p.Ile41Thr mutation of FIG4. The patients were categorized according to their phenotype. Six patients had a pure CMT; whereas, two patients had a CMT associated with parkinsonism. Three patients had an early onset and exhibited more severe forms of the disease. Three others experienced symptoms in their teenage years and had milder forms. Two patients had a late onset in adulthood. Four patients showed electrophysiological evidence of conduction blocks, typically associated with acquired neuropathies. Consequently, two of them received intravenous immunoglobulin treatment without a significant objective response. Interestingly, two heterozygous patients with the same mutations exhibited contrasting phenotypes, one having a severe early-onset form and the other experiencing a slow disease progression starting at the age of 49. Notably, although 7 out of 8 patients in this study were compound heterozygous for the p.Ile41Thr mutation, only one individual was found to be homozygous for this genetic variant and exhibited an early-onset, severe form of the disease. Additionally, one patient who developed the disease in his youth was also diagnosed with hereditary neuropathy with pressure palsies. Our findings provide insights into the CMT4J subtype by reporting on eight heterogeneous patient cases and highlight the potential for misdiagnosis when conduction blocks or asymmetrical nerve conduction study results are observed in patients with FIG4 mutations.
Disciplines :
Pediatrics
Author, co-author :
Beloribi-Djefaflia, Sadia; Reference Center for Neuromuscular Disorders and ALS, Timone University Hospital, Aix-Marseille University, 264 Rue Saint Pierre, 05 13385, Marseille, Cedex, France ; Filnemus, European Reference Network of Rare Diseases (ERN), Marseille, France
Morales, Raul Juntas; Neuromuscular Unit. Neurology Department, Vall d'Hebron University Hospital. Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
Fatehi, Farzad; Reference Center for Neuromuscular Disorders and ALS, Timone University Hospital, Aix-Marseille University, 264 Rue Saint Pierre, 05 13385, Marseille, Cedex, France ; Filnemus, European Reference Network of Rare Diseases (ERN), Marseille, France
Isapof, Arnaud; Pediatric Neurology Department, Reference Centre for Neuromuscular Diseases, Armand Trousseau Hospital, APHP, Sorbonne University, 26, Avenue du Docteur Arnold Netter, 75012, Paris, France
Servais, Laurent ; Université de Liège - ULiège > Département des sciences cliniques ; MDUK Oxford Neuromuscular Centre and NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
Leonard-Louis, Sarah; Neuromyology, Reference Center of Neuromuscular Disorders, Pitié Salpétrière Hospital, APHP, 47-83 Boulevard de L'Hôpital, 75651, Paris Cedex 13, France
Michaud, Maud; Reference Center for Neuromuscular Disorders, Central Nancy University Hospital, 29 Avenue Maréchal de Lattre de Tassigny, 54035, Nancy, France
Verdure, Pierre; Clinique Saint-Hilaire, 76000, Rouen, France
Gidaro, Teresa; I-Motion Institute, Hôpital Trousseau, Paris, France
Pouget, Jean; Reference Center for Neuromuscular Disorders and ALS, Timone University Hospital, Aix-Marseille University, 264 Rue Saint Pierre, 05 13385, Marseille, Cedex, France ; Filnemus, European Reference Network of Rare Diseases (ERN), Marseille, France ; Aix Marseille Université-Inserm UMR 1251, Medical Genetics and Functional Genomics, Marseille, France
Poinsignon, Vianney; Department of Molecular Genetics Pharmacogenomics and Hormonology, APHP, CHU de Bicêtre, 94276, Le Kremlin-Bicêtre, France
Bonello-Palot, Nathalie; Aix Marseille Université-Inserm UMR 1251, Medical Genetics and Functional Genomics, Marseille, France
Attarian, Shahram ; Reference Center for Neuromuscular Disorders and ALS, Timone University Hospital, Aix-Marseille University, 264 Rue Saint Pierre, 05 13385, Marseille, Cedex, France. shahram.attarian@ap-hm.fr ; Filnemus, European Reference Network of Rare Diseases (ERN), Marseille, France. shahram.attarian@ap-hm.fr ; Aix Marseille Université-Inserm UMR 1251, Medical Genetics and Functional Genomics, Marseille, France. shahram.attarian@ap-hm.fr
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