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Early-onset osteoarthritis, Charcot-Marie-Tooth like neuropathy, autoimmune features, multiple arterial aneurysms and dissections: an unrecognized and life threatening condition.

Aubart M, Gobert D, Aubart-Cohen F, Detaint D, Hanna N, d'Indya H, Lequintrec JS, Renard P, Vigneron AM, Dieudé P, Laissy JP, Koch P, Muti C, Roume J, Cusin V, Grandchamp B, Gouya L, LeGuern E, Papo T, Boileau C, Jondeau G - PLoS ONE (2014)

Bottom Line: 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.SMAD3 gene mutations are associated with aortic dilatation and osteoarthritis, but also autoimmunity and peripheral neuropathy which mimics type II Charcot-Marie-Tooth.

View Article: PubMed Central - PubMed

Affiliation: INSERM U698, Hôpital Bichat, Paris, France.

ABSTRACT

Background: Severe osteoarthritis and thoracic aortic aneurysms have recently been associated with mutations in the SMAD3 gene, but the full clinical spectrum is incompletely defined.

Methods: All 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.

Results: Thirty-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.

Interpretation: SMAD3 gene mutations are associated with aortic dilatation and osteoarthritis, but also autoimmunity and peripheral neuropathy which mimics type II Charcot-Marie-Tooth.

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Related in: MedlinePlus

Aortic features in different subgroups.Abdominal aortic dissection is abdominal aortic dissection not related to thoracic aortic dissection extension. Asymptomatic subjects are patients without demonstration of any feature.
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pone-0096387-g002: Aortic features in different subgroups.Abdominal aortic dissection is abdominal aortic dissection not related to thoracic aortic dissection extension. Asymptomatic subjects are patients without demonstration of any feature.

Mentions: Aortic features were studied in all 50 subjects (26 mutation carriers and 24 obligate mutation carriers) (Figure 2). Disease of the thoracic ascending aorta was present in 36/50 (dilatation leading or not to surgery, aortic dissection or sudden death), and led to an aortic event in 28 (aortic dissection, preventive aortic surgery and/or sudden death) at a mean age of 44.8 years. Thoracic aortic dilatation was evidenced in 30% of the non-operated patients (8/26), maximal at the level of the sinuses of Valsalva. Four patients (8%, 4/50) had a history of abdominal aortic dissection, isolated in one patient. Overall, 54% (28/50) displayed documented aortic disease (aneurysm, dissection, surgery) and an additional 18% (9/50) sudden death of unknown origin (total 74% [37/50]).


Early-onset osteoarthritis, Charcot-Marie-Tooth like neuropathy, autoimmune features, multiple arterial aneurysms and dissections: an unrecognized and life threatening condition.

Aubart M, Gobert D, Aubart-Cohen F, Detaint D, Hanna N, d'Indya H, Lequintrec JS, Renard P, Vigneron AM, Dieudé P, Laissy JP, Koch P, Muti C, Roume J, Cusin V, Grandchamp B, Gouya L, LeGuern E, Papo T, Boileau C, Jondeau G - PLoS ONE (2014)

Aortic features in different subgroups.Abdominal aortic dissection is abdominal aortic dissection not related to thoracic aortic dissection extension. Asymptomatic subjects are patients without demonstration of any feature.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4012990&req=5

pone-0096387-g002: Aortic features in different subgroups.Abdominal aortic dissection is abdominal aortic dissection not related to thoracic aortic dissection extension. Asymptomatic subjects are patients without demonstration of any feature.
Mentions: Aortic features were studied in all 50 subjects (26 mutation carriers and 24 obligate mutation carriers) (Figure 2). Disease of the thoracic ascending aorta was present in 36/50 (dilatation leading or not to surgery, aortic dissection or sudden death), and led to an aortic event in 28 (aortic dissection, preventive aortic surgery and/or sudden death) at a mean age of 44.8 years. Thoracic aortic dilatation was evidenced in 30% of the non-operated patients (8/26), maximal at the level of the sinuses of Valsalva. Four patients (8%, 4/50) had a history of abdominal aortic dissection, isolated in one patient. Overall, 54% (28/50) displayed documented aortic disease (aneurysm, dissection, surgery) and an additional 18% (9/50) sudden death of unknown origin (total 74% [37/50]).

Bottom Line: 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.SMAD3 gene mutations are associated with aortic dilatation and osteoarthritis, but also autoimmunity and peripheral neuropathy which mimics type II Charcot-Marie-Tooth.

View Article: PubMed Central - PubMed

Affiliation: INSERM U698, Hôpital Bichat, Paris, France.

ABSTRACT

Background: Severe osteoarthritis and thoracic aortic aneurysms have recently been associated with mutations in the SMAD3 gene, but the full clinical spectrum is incompletely defined.

Methods: All 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.

Results: Thirty-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.

Interpretation: SMAD3 gene mutations are associated with aortic dilatation and osteoarthritis, but also autoimmunity and peripheral neuropathy which mimics type II Charcot-Marie-Tooth.

Show MeSH
Related in: MedlinePlus