Loeys-Dietz syndrome.
Loeys-Dietz syndrome is an autosomal dominant aortic aneurysm syndrome characterized by multisystemic involvement. The most typical clinical triad includes hypertelorism, bifid uvula or cleft palate and aortic aneurysm with tortuosity. Natural history is significant for aortic dissection at smaller aortic diameter and arterial aneurysms throughout the arterial tree. The genetic cause is heterogeneous and includes mutations in genes encoding for components of the transforming growth factor beta (TGFβ) signalling pathway: TGFBR1, TGFBR2, SMAD3 and TGFB2. Despite the loss of function nature of these mutations, the patient-derived aortic tissues show evidence of increased (rather than decreased) TGFβ signalling. These insights offer new options for therapeutic interventions.
Center for Medical Genetics, Faculty of Medicine and Health Sciences, Antwerp University Hospital/University of Antwerp, Prins Boudewijnlaan 43, 2650, Antwerp, Belgium.
Lut
L
Van Laer
Harry
H
Dietz
Bart
B
Loeys
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001158:Arteries / Q000002:abnormalities / Q000473:pathology; D003937:Diagnosis, Differential; D004535:Ehlers-Danlos Syndrome / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D006801:Humans; D007593:Joint Instability / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D055947:Loeys-Dietz Syndrome / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D015398:Signal Transduction; D012873:Skin Diseases, Genetic / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D051900:Smad3 Protein / Q000235:genetics*; D053781:Transforming Growth Factor beta2 / Q000037:antagonists & inhibitors / Q000235:genetics*; D054079:Vascular Malformations / Q000175:diagnosis / Q000235:genetics / Q000473:pathology
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D057134:Antibodies, Neutralizing; D018125:Receptors, Transforming Growth Factor beta; C497790:SMAD3 protein, human; D051900:Smad3 Protein; C509041:TGFB2 protein, human; D053781:Transforming Growth Factor beta2; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625841:TGFBR1 protein, human