Early-Onset Osteoarthritis, Charcot-Marie-Tooth Like Neuropathy, Autoimmune Features, Multiple Arterial Aneurysms and Dissections: An Unrecognized and Life Threatening Condition

Autor: Bernard Grandchamp, Delphine Detaint, Eric LeGuern, Philippe Renard, Christine Muti, Anne-Marie Vigneron, Nadine Hanna, Fleur Aubart-Cohen, Laurent Gouya, Pierre Koch, Janine-Sophie Lequintrec, Catherine Boileau, Joelle Roume, Philippe Dieudé, Mélodie Aubart, Hyacintha d’Indya, Jean-Pierre Laissy, Thomas Papo, Veronica Cusin, Guillaume Jondeau, Delphine Gobert
Rok vydání: 2014
Předmět:
Male
Osteoarthritis
Vascular Medicine
Marfan Syndrome
Death
Sudden
Aortic aneurysm
Smad3 gene
Charcot-Marie-Tooth Disease
Medicine and Health Sciences
Medicine
Child
Multidisciplinary
Neuromuscular Diseases
Syndrome
Aneurysm dissecting
Middle Aged
Pedigree
Phenotype
Neurology
Child
Preschool
cardiovascular system
Female
Genetic Dominance
Research Article
Adult
medicine.medical_specialty
Adolescent
Science
Cardiology
Aortic Diseases
macromolecular substances
Autoimmune Diseases
Young Adult
Aneurysm
Rheumatology
medicine.artery
Autosomal Dominant Traits
Genetics
Humans
Smad3 Protein
Aged
Clinical Genetics
Aorta
Aortic Aneurysm
Thoracic
business.industry
Arthritis
Autosomal Dominant Diseases
Biology and Life Sciences
medicine.disease
Surgery
Aortic Dissection
Arterial aneurysms
Mutation
Early onset osteoarthritis
business
Zdroj: PLoS ONE
PLoS ONE, Vol 9, Iss 5, p e96387 (2014)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0096387
Popis: BackgroundSevere osteoarthritis and thoracic aortic aneurysms have recently been associated with mutations in the SMAD3 gene, but the full clinical spectrum is incompletely defined.MethodsAll SMAD3 gene mutation carriers coming to our centre and their families were investigated prospectively with a structured panel including standardized clinical workup, blood tests, total body computed tomography, joint X-rays. Electroneuromyography was performed in selected cases.ResultsThirty-four SMAD3 gene mutation carriers coming to our centre were identified and 16 relatives were considered affected because of aortic surgery or sudden death (total 50 subjects). Aortic disease was present in 72%, complicated with aortic dissection, surgery or sudden death in 56% at a mean age of 45 years. Aneurysm or tortuosity of the neck arteries was present in 78%, other arteries were affected in 44%, including dissection of coronary artery. Overall, 95% of mutation carriers displayed either aortic or extra-aortic arterial disease. Acrocyanosis was also present in the majority of patients. Osteoarticular manifestations were recorded in all patients. Joint involvement could be severe requiring surgery in young patients, of unusual localization such as tarsus or shoulder, or mimicking crystalline arthropathy with fibrocartilage calcifications. Sixty eight percent of patients displayed neurological symptoms, and 9 suffered peripheral neuropathy. Electroneuromyography revealed an axonal motor and sensory neuropathy in 3 different families, very evocative of type II Charcot-Marie-Tooth (CMT2) disease, although none had mutations in the known CMT2 genes. Autoimmune features including Sjogren's disease, rheumatoid arthritis, Hashimoto's disease, or isolated autoantibodies- were found in 36% of patients.InterpretationSMAD3 gene mutations are associated with aortic dilatation and osteoarthritis, but also autoimmunity and peripheral neuropathy which mimics type II Charcot-Marie-Tooth.
Databáze: OpenAIRE
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