Phenotypic spectrum of the SMAD3-related aneurysms–osteoarthritis syndrome

Laar, Ingrid M.B.H. van de; Linde, Denise van der; Oei, E.H.; Bos, P.K.; Bessems, J. H. J. M.; Bierma-Zeinstra, Sita M A; Meer, Belle L. van; Pals, Gerard; Oldenburg, Rogier A.; Bekkers, Jos A.; Moelker, Adriaan; Graaf, Bianca M. de; Mátyás, Gábor; Frohn-Mulder, Ingrid M.E.; Timmermans, Janneke; Hilhorst‐Hofstee, Yvonne; Cobben, Jan Maarten; Brüggenwirth, Hennie T.; Laer, Lut Van; Loeys, Bart; Backer, Julie De; Coucke, Paul; Dietz, Harry C.; Willems, Patrick J.; Oostra, Ben A.; Paepe, Anne De; Roos‐Hesselink, Jolien W.; Bertoli‐Avella, Aida M.; Wessels, Marja W.

doi:10.1136/jmedgenet-2011-100382

Cited by 223 publications

(194 citation statements)

References 41 publications

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“…These congenital heart malformations are only rarely seen in MFS. In LDS patients, pulmonary valve stenosis could also develop over time (21). Similar to MFS, MVP and mitral valve insufficiency are more frequently observed than in the general population (27,35), but appear to be somewhat less common in LDS compared to MFS (36).…”

Section: Cardiovascular Featuresmentioning

confidence: 99%

“…Besides aneurysms affecting the aortic root, LDS is known for its involvement of aneurysms affecting arterial branches of head, neck, lung, lower extremities, and thoracic and abdominal aorta (21,27,33). Dissection of the coronary artery and the internal iliac and superior mesenteric artery have been described without prior dilatation (21,34). Impaired left ventricular systolic function could be the consequence of coronary artery dissection (12).…”

Section: Cardiovascular Featuresmentioning

confidence: 99%

“…With increasing age, left ventricular hypertrophy and atrial fibrillation could develop (21,27), which are both uncommon in MFS. Arterial tortuosity is most prominently affecting the vessels of the head, neck and aorta, but also affects other thoracic and abdominal arteries or can be generalized (21,27,37,38).…”

Section: Cardiovascular Featuresmentioning

confidence: 99%

“…Arterial tortuosity is most prominently affecting the vessels of the head, neck and aorta, but also affects other thoracic and abdominal arteries or can be generalized (21,27,37,38). Cerebrovascular anomalies are frequently diagnosed and include tortuosity, affecting vertebral, internal carotid, cerebral and pericallosal arteries and intracranial aneurysms, typically affecting the vertebral, carotid, basilar, and ophthalmic arteries (21).…”

Section: Cardiovascular Featuresmentioning

confidence: 99%

“…A highly arched palate and bifid uvula, a milder presentation of a cleft palate, are frequently observed (21). Alternatively, the uvula can also have a broad appearance.…”

Section: Craniofacial Featuresmentioning

confidence: 99%

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Differences in manifestations of Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome

Meester

Verstraeten

Schepers

et al. 2017

Ann. Cardiothorac. Surg.

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228

184

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Many different heritable connective tissue disorders (HCTD) have been described over the past decades.These syndromes often affect the connective tissue of various organ systems, including heart, blood vessels, skin, joints, bone, eyes, and lungs. The discovery of these HCTD was followed by the identification of mutations in a wide range of genes encoding structural proteins, modifying enzymes, or components of the In contrast, no association is reported between LDS and the presence of ectopia lentis, a key distinguishing feature of MFS. Overlapping features between MFS and LDS include scoliosis, pes planus, anterior chest deformity, spontaneous pneumothorax, and dural ectasia. EDS refers to a group of clinically and genetically heterogeneous connective tissue disorders and all subtypes are characterized by variable abnormalities of skin, ligaments and joints, blood vessels, and internal organs. Typical presenting features include joint hypermobility, skin hyperextensibility, and tissue fragility. Up to one quarter of the EDS patients show aortic aneurysmal disease. The latest EDS nosology distinguishes 13 subtypes. Many phenotypic features show overlap between the different subtypes, which makes the clinical diagnosis rather difficult and highlights the importance of molecular diagnostic confirmation.

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Section: Cardiovascular Featuresmentioning

confidence: 99%

Section: Cardiovascular Featuresmentioning

confidence: 99%

Section: Cardiovascular Featuresmentioning

confidence: 99%

Section: Cardiovascular Featuresmentioning

confidence: 99%

“…A highly arched palate and bifid uvula, a milder presentation of a cleft palate, are frequently observed (21). Alternatively, the uvula can also have a broad appearance.…”

Section: Craniofacial Featuresmentioning

confidence: 99%

See 3 more Smart Citations

Differences in manifestations of Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome

Meester

Verstraeten

Schepers

et al. 2017

Ann. Cardiothorac. Surg.

Self Cite

228

184

View full text Add to dashboard Cite

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Genetics of Hereditary Large Vessel Diseases

Morisaki

2017

Encyclopedia of Life Sciences

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Recently, the genetic study of hereditary large vessel diseases such as Marfan syndrome has been advanced, leading to not only identifying pathogenic genes but also providing information of the pathophysiology and possible new therapeutic targets. Genes identified for hereditary large vessel diseases include FBN1 , TGFBR1 , TGFBR2 , SMAD3 , TGFB2 , TGFB3 , SKI , EFEMP2 , BGN , COL3A1 , FLNA , ACTA2 , MYH11 , MYLK , SLC2A10 and NOTCH1 . Dysfunction of these genes is mainly connected with altered function of transforming growth factor‐β (TGF‐β) signalling pathways, as well as that of the extracellular matrix or smooth muscle contractile apparatus, resulting in progression of structural abnormality to aorta and large vessels including aortic aneurysms and dissections. Furthermore, it has been shown that the TGF‐β signalling pathway plays a key role in the pathogenesis of Marfan syndrome and Loeys–Dietz syndrome, which may be important for development of strategies for medical and surgical treatment of hereditary large vessel diseases. Key Concepts Genetic study of hereditary large vessel diseases has been advanced. Young patients with large vessel diseases should be aware of possible genetic disease. Alteration of transforming growth factor‐β (TGF‐β) signalling pathways as well as that of the extracellular matrix or smooth muscle contractile apparatus is closely connected with large vessel diseases. Genetic study of hereditary large vessel diseases may help to get better therapeutic approach in the near future. Medical treatment modulating TGF‐β signaling would be effective for hereditary large vessel diseases.

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