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Thoracic Aortic Aneurysm in Infancy in Aneurysms– O steoarthritis Syndrome Due to a Novel SMAD 3 Mutation: Further Delineation of the Phenotype
Author(s) -
Wischmeijer Anita,
Van Laer Lut,
Tortora Giada,
Bolar Nikhita Ajit,
Van Camp Guy,
Fransen Erik,
Peeters Nils,
di Bartolomeo Roberto,
Pacini Davide,
Gargiulo Gaetano,
Turci Simone,
Bonvicini Marco,
Mariucci Elisabetta,
Lovato Luigi,
Brusori Stefano,
Ritelli Marco,
Colombi Marina,
Garavelli Livia,
Seri Marco,
Loeys Bart L.
Publication year - 2013
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.35852
Subject(s) - medicine , aneurysm , aortic aneurysm , marfan syndrome , thoracic aortic aneurysm , thoracic aorta , aorta , cardiology , surgery
Recently, mutations in the SMAD3 gene were found to cause a new autosomal dominant aneurysm condition similar to Loeys–Dietz syndrome (LDS), mostly with osteoarthritis, called aneurysms–osteoarthritis syndrome (AOS). Our 3‐year‐old propositus underwent correction of an inguinal hernia at 3 months and substitution of the ascending aorta for pathologic dilation at 12 months of age. Family history reveals aortic dilation in his mother at 30 years, death due to aortic dissection of an 18‐year‐old maternal aunt, surgical replacement of the ascending aorta because of aneurysm in a maternal uncle at 19 years, postpartum death of the maternal grandmother at 24 years and surgical intervention because of thoracic aortic aneurysm in a brother of the propositus' grandmother at 54 years. The affected individuals present with several other signs of connective tissue disease, but the two adult patients evaluated revealed no radiologic evidence of osteoarthritis. Molecular testing of the TGFBR1 and TGFBR2 genes, involved in LDS, resulted negative, but analysis of SMAD3 disclosed the novel heterozygous loss‐of‐function mutation c.1170_1179del (p.Ser391AlafsX7) in exon 9 in all affected family members, confirming the diagnosis of AOS. SMAD3 mutations should be considered in patients of all ages with LDS‐like phenotypes and negative TGFBR1/2 molecular tests, especially in the presence of aortic root or ascending aortic aneurysms, even though signs of early onset osteoarthritis are absent. © 2013 Wiley Periodicals, Inc.