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Total Aortic Replacement in Loeys-Dietz Syndrome

2009; Elsevier BV; Volume: 87; Issue: 6 Linguagem: Inglês

10.1016/j.athoracsur.2008.10.049

1552-6259

J. Scott Rankin, Alan C. Braverman, Nicholas T. Kouchoukos,

Aortic aneurysm repair treatments

Loeys-Dietz syndrome presents early in life with rapidly progressive aortic aneurysmal disease, hypertelorism, and bifid uvula/cleft palate. Genetic testing reveals transforming growth factor-β 1 and 2 mutations. Patients require monitoring for progressive aneurysmal disease, and may need total aortic replacement. Two patients are presented who typify these concepts. Loeys-Dietz syndrome presents early in life with rapidly progressive aortic aneurysmal disease, hypertelorism, and bifid uvula/cleft palate. Genetic testing reveals transforming growth factor-β 1 and 2 mutations. Patients require monitoring for progressive aneurysmal disease, and may need total aortic replacement. Two patients are presented who typify these concepts. Inherited connective tissue disorders are associated with aortic aneurysms and dissections. Marfan syndrome is an example, in which mutation of the FBN1 gene encoding the protein fibrillin-1 causes the associated defects [1Dietz H.C. Cutting G. Pyeritz R. et al.Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene.Nature. 1991; 352: 337-339Crossref PubMed Scopus (1581) Google Scholar]. Recently, another genetic complex, Loeys-Dietz syndrome (LDS), has been described, and is characterized by rapidly progressive and generalized aortic and branch vessel disease, hypertelorism, and bifid uvula/cleft palate [2Loeys B.L. Schwarze U. Holm T. et al.Aneurysm syndromes caused by mutations in the TGF-β receptor.N Engl J Med. 2006; 355: 788-798Crossref PubMed Scopus (1229) Google Scholar]. Loeys-Dietz syndrome carries a worse prognosis than Marfan syndrome, with an average age for aortic surgery of 17 years and a life expectancy of 23 years in the earliest series [2Loeys B.L. Schwarze U. Holm T. et al.Aneurysm syndromes caused by mutations in the TGF-β receptor.N Engl J Med. 2006; 355: 788-798Crossref PubMed Scopus (1229) Google Scholar]. Thus, a better understanding of LDS and its clinical implications is important. In this report, two patients are described who exhibited clinical characteristics of LDS and required extensive staged replacement of the aorta at a young age.Case ReportsPatient 1In 2006, a 22-year-old woman experienced an acute type A aortic dissection diagnosed by computed tomography (CT) scanning, likely superimposed on a preexisting aortic root aneurysm (Fig 1). She had a history of bilateral club foot repair and was considered to have vascular Ehlers-Danlos syndrome, but this had not been confirmed by genetic testing. Pectus carinatum was noted on examination, and she was hemodynamically stable. She underwent emergency aortic root replacement using a valve-graft conduit. Recovery was uneventful, and a predischarge CT scan showed satisfactory appearance of the conduit and a 3.5-cm diameter patent distal aortic false lumen extending into the abdomen. She was placed on a regimen of beta-blocker and antihypertensive therapy and scheduled for follow-up CT examination in 6 months.Three months postoperatively, the patient complained of vague back pain, and a CT scan showed that the entire patent distal false lumen, from the aortic arch to the iliac bifurcation, had enlarged, with a maximum diameter of 6 cm in the descending aorta. She underwent graft replacement of the remaining thoracic aorta to the level of the T-9 intercostal arteries using a clam shell approach and profound hypothermia [3Kouchoukos N.T. Mauney M.C. Masetti P. et al.Single-stage repair of extensive thoracic aortic aneurysms: experience with the arch-first technique and bilateral anterior thoracotomy.J Thorac Cardiovasc Surg. 2004; 128: 669-676PubMed Scopus (73) Google Scholar]. The proximal anastomosis was to the valve-graft conduit, the brachiocephalic vessels were attached with separate grafts, and the distal aorta was fenestrated to permit perfusion of both lumens. She recovered uneventfully, and CT imaging showed a satisfactory result. She was scheduled for further evaluation of the remaining aorta in 3 months.Within 1 month, the patient complained of lower back pain, and CT imaging showed continued expansion of the false lumen. She was readmitted, and underwent replacement of the remaining thoracic and the entire abdominal aorta using a retroperitoneal flank incision and profound hypothermia [4Kouchoukos N.T. Masetti P. Rokkas C.K. et al.Hypothermic cardiopulmonary bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta.Ann Thorac Surg. 2002; 74: 1885-1887Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar]. Three pairs of distal intercostal arteries were reimplanted into the graft, and the visceral and renal arteries were revascularized with individual branch grafts. Recovery was uneventful, and postoperative imaging was satisfactory. Subsequent physical examination identified a bifid uvula, and genetic testing revealed a transforming growth factor (TGF)-β 2 mutation, confirming the diagnosis of LDS. The patient continues to do well 1 year postoperatively, and has returned to college to pursue a medical career.Patient 2In 1995, a 15-year-old girl underwent aortic root replacement for an aortic root aneurysm using a valve-graft conduit, and was thought to have Marfan syndrome. In 2004, aneurysmal dilation of her distal ascending aorta, arch, and proximal descending aorta developed. She underwent single-stage replacement of these segments using a clam shell incision and profound hypothermia. In 2006, a large aneurysm of the remaining descending aorta developed, and she underwent replacement to the level of the T-10 intercostal arteries using profound hypothermia and circulatory arrest. Her recovery was uncomplicated, and she remains well on a regimen of beta-blocker therapy. Genetic testing revealed a TGF-β 1 mutation, confirming the diagnosis of LDS. The patient is being followed with CT scans every 6 months to monitor the remaining aorta.CommentBased on clinical experience, it has been suggested that variants of genetic aneurysmal disease similar to but distinct from Marfan syndrome exist [5Wolfe W.G. Oldham H.N. Rankin J.S. et al.Surgical treatment of acute ascending aortic dissection.Ann Surg. 1983; 197: 738-742Crossref PubMed Scopus (39) Google Scholar]. Recently, several genetic mutations have been shown to account for a variety of aneurysmal disorders. While several, such as bicuspid aortic valve disease [6Braverman A.C. Guven H. Beardslee M.A. et al.The bicuspid aortic valve.Curr Prob Cardiol. 2005; 30: 461-522Abstract Full Text Full Text PDF Google Scholar] and familial thoracic aortic aneurysm and dissection syndromes [7Pannu H. Avidan N. Tran-Fadulu V. Milewicz D.M. Genetic basis of thoracic aortic aneurysms and dissections: potential relevance to abdominal aortic aneurysms.Ann NY Acad Sci. 2006; 1085: 242-255Crossref PubMed Scopus (38) Google Scholar], are continuing to be characterized, LDS is known to be caused by mutations in the TGF-β receptor [2Loeys B.L. Schwarze U. Holm T. et al.Aneurysm syndromes caused by mutations in the TGF-β receptor.N Engl J Med. 2006; 355: 788-798Crossref PubMed Scopus (1229) Google Scholar]. Mutations in this receptor increase downstream signaling of the cytokine TGF-β in blood vessels, leading to overproduction of collagen, loss of elastin content, and disarray of elastic fibers. These patients often carry alternative diagnoses initially, as ours did. When compared with Marfan syndrome, the vascular disease in LDS tends to be generalized and has an especially malignant natural history. Many patients present in childhood or young adulthood [8Williams J.A. Loeys B.L. Nwakanma L.U. et al.Early surgical experience with Loeys-Dietz: a new syndrome of aggressive thoracic aortic aneurysm disease.Ann Thorac Surg. 2007; 83: 757-763Abstract Full Text Full Text PDF Scopus (209) Google Scholar, 9Lee R.S. Fazel S. Schwarze U. et al.Rapid aneurysmal degeneration of a Stanford type B aortic dissection in a patient with Loeys-Dietz syndrome.J Thorac Cardiovasc Surg. 2007; 134: 242-243Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar]. Rupture can occur at an early age or at aortic diameters that ordinarily would not be predictive of this complication. Once the diagnosis is made, frequent aortic imaging is indicated, and aneurysmal progression may be especially rapid after aortic dissection, as occurred in our first patient. Staged replacement of affected aortic segments is indicated, sometimes leading to replacement of the entire aorta, as in patient 1. Because the disorder is autosomal dominant with variable clinical expression, genetic counseling and screening of family members is recommended.Total aortic replacement is a major surgical procedure that has carried significant mortality and morbidity in the past. Recent advances in intraoperative management have greatly improved outcomes [3Kouchoukos N.T. Mauney M.C. Masetti P. et al.Single-stage repair of extensive thoracic aortic aneurysms: experience with the arch-first technique and bilateral anterior thoracotomy.J Thorac Cardiovasc Surg. 2004; 128: 669-676PubMed Scopus (73) Google Scholar, 4Kouchoukos N.T. Masetti P. Rokkas C.K. et al.Hypothermic cardiopulmonary bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta.Ann Thorac Surg. 2002; 74: 1885-1887Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar]. Profound hypothermia is ideal for organ protection, not only for the brain but also for the spinal chord and abdominal organs. Continuous perfusion of the cerebral vasculature through axillary artery cannulation during arch replacement has minimized the duration of circulatory arrest, and greatly reduced the incidence of neurologic injury [3Kouchoukos N.T. Mauney M.C. Masetti P. et al.Single-stage repair of extensive thoracic aortic aneurysms: experience with the arch-first technique and bilateral anterior thoracotomy.J Thorac Cardiovasc Surg. 2004; 128: 669-676PubMed Scopus (73) Google Scholar]. Hypothermic protection of the spinal cord, together with routine reimplantation of distal thoracic intercostal/lumbar arteries, has been associated with a low incidence of paraplegia [4Kouchoukos N.T. Masetti P. Rokkas C.K. et al.Hypothermic cardiopulmonary bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta.Ann Thorac Surg. 2002; 74: 1885-1887Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar]. Likewise, hypothermic protection of the kidneys and abdominal viscera has reduced the incidence of organ failure. The clam shell incision has allowed larger segments of aorta to be replaced in a single stage, thus reducing the number of operations required.In summary, LDS is caused by mutations in the TGF-β receptor 1 and 2 genes, and is characterized by progressive aortic aneurysmal disease and dissection. Patients present at an early age and require vigilant monitoring of all vascular segments because of the rapidly progressive nature of the aortic disease. Surgical management using new supportive strategies is likely to produce better long-term outcomes, and total aortic replacement may be necessary. Inherited connective tissue disorders are associated with aortic aneurysms and dissections. Marfan syndrome is an example, in which mutation of the FBN1 gene encoding the protein fibrillin-1 causes the associated defects [1Dietz H.C. Cutting G. Pyeritz R. et al.Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene.Nature. 1991; 352: 337-339Crossref PubMed Scopus (1581) Google Scholar]. Recently, another genetic complex, Loeys-Dietz syndrome (LDS), has been described, and is characterized by rapidly progressive and generalized aortic and branch vessel disease, hypertelorism, and bifid uvula/cleft palate [2Loeys B.L. Schwarze U. Holm T. et al.Aneurysm syndromes caused by mutations in the TGF-β receptor.N Engl J Med. 2006; 355: 788-798Crossref PubMed Scopus (1229) Google Scholar]. Loeys-Dietz syndrome carries a worse prognosis than Marfan syndrome, with an average age for aortic surgery of 17 years and a life expectancy of 23 years in the earliest series [2Loeys B.L. Schwarze U. Holm T. et al.Aneurysm syndromes caused by mutations in the TGF-β receptor.N Engl J Med. 2006; 355: 788-798Crossref PubMed Scopus (1229) Google Scholar]. Thus, a better understanding of LDS and its clinical implications is important. In this report, two patients are described who exhibited clinical characteristics of LDS and required extensive staged replacement of the aorta at a young age. Case ReportsPatient 1In 2006, a 22-year-old woman experienced an acute type A aortic dissection diagnosed by computed tomography (CT) scanning, likely superimposed on a preexisting aortic root aneurysm (Fig 1). She had a history of bilateral club foot repair and was considered to have vascular Ehlers-Danlos syndrome, but this had not been confirmed by genetic testing. Pectus carinatum was noted on examination, and she was hemodynamically stable. She underwent emergency aortic root replacement using a valve-graft conduit. Recovery was uneventful, and a predischarge CT scan showed satisfactory appearance of the conduit and a 3.5-cm diameter patent distal aortic false lumen extending into the abdomen. She was placed on a regimen of beta-blocker and antihypertensive therapy and scheduled for follow-up CT examination in 6 months.Three months postoperatively, the patient complained of vague back pain, and a CT scan showed that the entire patent distal false lumen, from the aortic arch to the iliac bifurcation, had enlarged, with a maximum diameter of 6 cm in the descending aorta. She underwent graft replacement of the remaining thoracic aorta to the level of the T-9 intercostal arteries using a clam shell approach and profound hypothermia [3Kouchoukos N.T. Mauney M.C. Masetti P. et al.Single-stage repair of extensive thoracic aortic aneurysms: experience with the arch-first technique and bilateral anterior thoracotomy.J Thorac Cardiovasc Surg. 2004; 128: 669-676PubMed Scopus (73) Google Scholar]. The proximal anastomosis was to the valve-graft conduit, the brachiocephalic vessels were attached with separate grafts, and the distal aorta was fenestrated to permit perfusion of both lumens. She recovered uneventfully, and CT imaging showed a satisfactory result. She was scheduled for further evaluation of the remaining aorta in 3 months.Within 1 month, the patient complained of lower back pain, and CT imaging showed continued expansion of the false lumen. She was readmitted, and underwent replacement of the remaining thoracic and the entire abdominal aorta using a retroperitoneal flank incision and profound hypothermia [4Kouchoukos N.T. Masetti P. Rokkas C.K. et al.Hypothermic cardiopulmonary bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta.Ann Thorac Surg. 2002; 74: 1885-1887Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar]. Three pairs of distal intercostal arteries were reimplanted into the graft, and the visceral and renal arteries were revascularized with individual branch grafts. Recovery was uneventful, and postoperative imaging was satisfactory. Subsequent physical examination identified a bifid uvula, and genetic testing revealed a transforming growth factor (TGF)-β 2 mutation, confirming the diagnosis of LDS. The patient continues to do well 1 year postoperatively, and has returned to college to pursue a medical career.Patient 2In 1995, a 15-year-old girl underwent aortic root replacement for an aortic root aneurysm using a valve-graft conduit, and was thought to have Marfan syndrome. In 2004, aneurysmal dilation of her distal ascending aorta, arch, and proximal descending aorta developed. She underwent single-stage replacement of these segments using a clam shell incision and profound hypothermia. In 2006, a large aneurysm of the remaining descending aorta developed, and she underwent replacement to the level of the T-10 intercostal arteries using profound hypothermia and circulatory arrest. Her recovery was uncomplicated, and she remains well on a regimen of beta-blocker therapy. Genetic testing revealed a TGF-β 1 mutation, confirming the diagnosis of LDS. The patient is being followed with CT scans every 6 months to monitor the remaining aorta. Patient 1In 2006, a 22-year-old woman experienced an acute type A aortic dissection diagnosed by computed tomography (CT) scanning, likely superimposed on a preexisting aortic root aneurysm (Fig 1). She had a history of bilateral club foot repair and was considered to have vascular Ehlers-Danlos syndrome, but this had not been confirmed by genetic testing. Pectus carinatum was noted on examination, and she was hemodynamically stable. She underwent emergency aortic root replacement using a valve-graft conduit. Recovery was uneventful, and a predischarge CT scan showed satisfactory appearance of the conduit and a 3.5-cm diameter patent distal aortic false lumen extending into the abdomen. She was placed on a regimen of beta-blocker and antihypertensive therapy and scheduled for follow-up CT examination in 6 months.Three months postoperatively, the patient complained of vague back pain, and a CT scan showed that the entire patent distal false lumen, from the aortic arch to the iliac bifurcation, had enlarged, with a maximum diameter of 6 cm in the descending aorta. She underwent graft replacement of the remaining thoracic aorta to the level of the T-9 intercostal arteries using a clam shell approach and profound hypothermia [3Kouchoukos N.T. Mauney M.C. Masetti P. et al.Single-stage repair of extensive thoracic aortic aneurysms: experience with the arch-first technique and bilateral anterior thoracotomy.J Thorac Cardiovasc Surg. 2004; 128: 669-676PubMed Scopus (73) Google Scholar]. The proximal anastomosis was to the valve-graft conduit, the brachiocephalic vessels were attached with separate grafts, and the distal aorta was fenestrated to permit perfusion of both lumens. She recovered uneventfully, and CT imaging showed a satisfactory result. She was scheduled for further evaluation of the remaining aorta in 3 months.Within 1 month, the patient complained of lower back pain, and CT imaging showed continued expansion of the false lumen. She was readmitted, and underwent replacement of the remaining thoracic and the entire abdominal aorta using a retroperitoneal flank incision and profound hypothermia [4Kouchoukos N.T. Masetti P. Rokkas C.K. et al.Hypothermic cardiopulmonary bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta.Ann Thorac Surg. 2002; 74: 1885-1887Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar]. Three pairs of distal intercostal arteries were reimplanted into the graft, and the visceral and renal arteries were revascularized with individual branch grafts. Recovery was uneventful, and postoperative imaging was satisfactory. Subsequent physical examination identified a bifid uvula, and genetic testing revealed a transforming growth factor (TGF)-β 2 mutation, confirming the diagnosis of LDS. The patient continues to do well 1 year postoperatively, and has returned to college to pursue a medical career. In 2006, a 22-year-old woman experienced an acute type A aortic dissection diagnosed by computed tomography (CT) scanning, likely superimposed on a preexisting aortic root aneurysm (Fig 1). She had a history of bilateral club foot repair and was considered to have vascular Ehlers-Danlos syndrome, but this had not been confirmed by genetic testing. Pectus carinatum was noted on examination, and she was hemodynamically stable. She underwent emergency aortic root replacement using a valve-graft conduit. Recovery was uneventful, and a predischarge CT scan showed satisfactory appearance of the conduit and a 3.5-cm diameter patent distal aortic false lumen extending into the abdomen. She was placed on a regimen of beta-blocker and antihypertensive therapy and scheduled for follow-up CT examination in 6 months. Three months postoperatively, the patient complained of vague back pain, and a CT scan showed that the entire patent distal false lumen, from the aortic arch to the iliac bifurcation, had enlarged, with a maximum diameter of 6 cm in the descending aorta. She underwent graft replacement of the remaining thoracic aorta to the level of the T-9 intercostal arteries using a clam shell approach and profound hypothermia [3Kouchoukos N.T. Mauney M.C. Masetti P. et al.Single-stage repair of extensive thoracic aortic aneurysms: experience with the arch-first technique and bilateral anterior thoracotomy.J Thorac Cardiovasc Surg. 2004; 128: 669-676PubMed Scopus (73) Google Scholar]. The proximal anastomosis was to the valve-graft conduit, the brachiocephalic vessels were attached with separate grafts, and the distal aorta was fenestrated to permit perfusion of both lumens. She recovered uneventfully, and CT imaging showed a satisfactory result. She was scheduled for further evaluation of the remaining aorta in 3 months. Within 1 month, the patient complained of lower back pain, and CT imaging showed continued expansion of the false lumen. She was readmitted, and underwent replacement of the remaining thoracic and the entire abdominal aorta using a retroperitoneal flank incision and profound hypothermia [4Kouchoukos N.T. Masetti P. Rokkas C.K. et al.Hypothermic cardiopulmonary bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta.Ann Thorac Surg. 2002; 74: 1885-1887Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar]. Three pairs of distal intercostal arteries were reimplanted into the graft, and the visceral and renal arteries were revascularized with individual branch grafts. Recovery was uneventful, and postoperative imaging was satisfactory. Subsequent physical examination identified a bifid uvula, and genetic testing revealed a transforming growth factor (TGF)-β 2 mutation, confirming the diagnosis of LDS. The patient continues to do well 1 year postoperatively, and has returned to college to pursue a medical career. Patient 2In 1995, a 15-year-old girl underwent aortic root replacement for an aortic root aneurysm using a valve-graft conduit, and was thought to have Marfan syndrome. In 2004, aneurysmal dilation of her distal ascending aorta, arch, and proximal descending aorta developed. She underwent single-stage replacement of these segments using a clam shell incision and profound hypothermia. In 2006, a large aneurysm of the remaining descending aorta developed, and she underwent replacement to the level of the T-10 intercostal arteries using profound hypothermia and circulatory arrest. Her recovery was uncomplicated, and she remains well on a regimen of beta-blocker therapy. Genetic testing revealed a TGF-β 1 mutation, confirming the diagnosis of LDS. The patient is being followed with CT scans every 6 months to monitor the remaining aorta. In 1995, a 15-year-old girl underwent aortic root replacement for an aortic root aneurysm using a valve-graft conduit, and was thought to have Marfan syndrome. In 2004, aneurysmal dilation of her distal ascending aorta, arch, and proximal descending aorta developed. She underwent single-stage replacement of these segments using a clam shell incision and profound hypothermia. In 2006, a large aneurysm of the remaining descending aorta developed, and she underwent replacement to the level of the T-10 intercostal arteries using profound hypothermia and circulatory arrest. Her recovery was uncomplicated, and she remains well on a regimen of beta-blocker therapy. Genetic testing revealed a TGF-β 1 mutation, confirming the diagnosis of LDS. The patient is being followed with CT scans every 6 months to monitor the remaining aorta. CommentBased on clinical experience, it has been suggested that variants of genetic aneurysmal disease similar to but distinct from Marfan syndrome exist [5Wolfe W.G. Oldham H.N. Rankin J.S. et al.Surgical treatment of acute ascending aortic dissection.Ann Surg. 1983; 197: 738-742Crossref PubMed Scopus (39) Google Scholar]. Recently, several genetic mutations have been shown to account for a variety of aneurysmal disorders. While several, such as bicuspid aortic valve disease [6Braverman A.C. Guven H. Beardslee M.A. et al.The bicuspid aortic valve.Curr Prob Cardiol. 2005; 30: 461-522Abstract Full Text Full Text PDF Google Scholar] and familial thoracic aortic aneurysm and dissection syndromes [7Pannu H. Avidan N. Tran-Fadulu V. Milewicz D.M. Genetic basis of thoracic aortic aneurysms and dissections: potential relevance to abdominal aortic aneurysms.Ann NY Acad Sci. 2006; 1085: 242-255Crossref PubMed Scopus (38) Google Scholar], are continuing to be characterized, LDS is known to be caused by mutations in the TGF-β receptor [2Loeys B.L. Schwarze U. Holm T. et al.Aneurysm syndromes caused by mutations in the TGF-β receptor.N Engl J Med. 2006; 355: 788-798Crossref PubMed Scopus (1229) Google Scholar]. Mutations in this receptor increase downstream signaling of the cytokine TGF-β in blood vessels, leading to overproduction of collagen, loss of elastin content, and disarray of elastic fibers. These patients often carry alternative diagnoses initially, as ours did. When compared with Marfan syndrome, the vascular disease in LDS tends to be generalized and has an especially malignant natural history. Many patients present in childhood or young adulthood [8Williams J.A. Loeys B.L. Nwakanma L.U. et al.Early surgical experience with Loeys-Dietz: a new syndrome of aggressive thoracic aortic aneurysm disease.Ann Thorac Surg. 2007; 83: 757-763Abstract Full Text Full Text PDF Scopus (209) Google Scholar, 9Lee R.S. Fazel S. Schwarze U. et al.Rapid aneurysmal degeneration of a Stanford type B aortic dissection in a patient with Loeys-Dietz syndrome.J Thorac Cardiovasc Surg. 2007; 134: 242-243Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar]. Rupture can occur at an early age or at aortic diameters that ordinarily would not be predictive of this complication. Once the diagnosis is made, frequent aortic imaging is indicated, and aneurysmal progression may be especially rapid after aortic dissection, as occurred in our first patient. Staged replacement of affected aortic segments is indicated, sometimes leading to replacement of the entire aorta, as in patient 1. Because the disorder is autosomal dominant with variable clinical expression, genetic counseling and screening of family members is recommended.Total aortic replacement is a major surgical procedure that has carried significant mortality and morbidity in the past. Recent advances in intraoperative management have greatly improved outcomes [3Kouchoukos N.T. Mauney M.C. Masetti P. et al.Single-stage repair of extensive thoracic aortic aneurysms: experience with the arch-first technique and bilateral anterior thoracotomy.J Thorac Cardiovasc Surg. 2004; 128: 669-676PubMed Scopus (73) Google Scholar, 4Kouchoukos N.T. Masetti P. Rokkas C.K. et al.Hypothermic cardiopulmonary bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta.Ann Thorac Surg. 2002; 74: 1885-1887Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar]. Profound hypothermia is ideal for organ protection, not only for the brain but also for the spinal chord and abdominal organs. Continuous perfusion of the cerebral vasculature through axillary artery cannulation during arch replacement has minimized the duration of circulatory arrest, and greatly reduced the incidence of neurologic injury [3Kouchoukos N.T. Mauney M.C. Masetti P. et al.Single-stage repair of extensive thoracic aortic aneurysms: experience with the arch-first technique and bilateral anterior thoracotomy.J Thorac Cardiovasc Surg. 2004; 128: 669-676PubMed Scopus (73) Google Scholar]. Hypothermic protection of the spinal cord, together with routine reimplantation of distal thoracic intercostal/lumbar arteries, has been associated with a low incidence of paraplegia [4Kouchoukos N.T. Masetti P. Rokkas C.K. et al.Hypothermic cardiopulmonary bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta.Ann Thorac Surg. 2002; 74: 1885-1887Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar]. Likewise, hypothermic protection of the kidneys and abdominal viscera has reduced the incidence of organ failure. The clam shell incision has allowed larger segments of aorta to be replaced in a single stage, thus reducing the number of operations required.In summary, LDS is caused by mutations in the TGF-β receptor 1 and 2 genes, and is characterized by progressive aortic aneurysmal disease and dissection. Patients present at an early age and require vigilant monitoring of all vascular segments because of the rapidly progressive nature of the aortic disease. Surgical management using new supportive strategies is likely to produce better long-term outcomes, and total aortic replacement may be necessary. Based on clinical experience, it has been suggested that variants of genetic aneurysmal disease similar to but distinct from Marfan syndrome exist [5Wolfe W.G. Oldham H.N. Rankin J.S. et al.Surgical treatment of acute ascending aortic dissection.Ann Surg. 1983; 197: 738-742Crossref PubMed Scopus (39) Google Scholar]. Recently, several genetic mutations have been shown to account for a variety of aneurysmal disorders. While several, such as bicuspid aortic valve disease [6Braverman A.C. Guven H. Beardslee M.A. et al.The bicuspid aortic valve.Curr Prob Cardiol. 2005; 30: 461-522Abstract Full Text Full Text PDF Google Scholar] and familial thoracic aortic aneurysm and dissection syndromes [7Pannu H. Avidan N. Tran-Fadulu V. Milewicz D.M. Genetic basis of thoracic aortic aneurysms and dissections: potential relevance to abdominal aortic aneurysms.Ann NY Acad Sci. 2006; 1085: 242-255Crossref PubMed Scopus (38) Google Scholar], are continuing to be characterized, LDS is known to be caused by mutations in the TGF-β receptor [2Loeys B.L. Schwarze U. Holm T. et al.Aneurysm syndromes caused by mutations in the TGF-β receptor.N Engl J Med. 2006; 355: 788-798Crossref PubMed Scopus (1229) Google Scholar]. Mutations in this receptor increase downstream signaling of the cytokine TGF-β in blood vessels, leading to overproduction of collagen, loss of elastin content, and disarray of elastic fibers. These patients often carry alternative diagnoses initially, as ours did. When compared with Marfan syndrome, the vascular disease in LDS tends to be generalized and has an especially malignant natural history. Many patients present in childhood or young adulthood [8Williams J.A. Loeys B.L. Nwakanma L.U. et al.Early surgical experience with Loeys-Dietz: a new syndrome of aggressive thoracic aortic aneurysm disease.Ann Thorac Surg. 2007; 83: 757-763Abstract Full Text Full Text PDF Scopus (209) Google Scholar, 9Lee R.S. Fazel S. Schwarze U. et al.Rapid aneurysmal degeneration of a Stanford type B aortic dissection in a patient with Loeys-Dietz syndrome.J Thorac Cardiovasc Surg. 2007; 134: 242-243Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar]. Rupture can occur at an early age or at aortic diameters that ordinarily would not be predictive of this complication. Once the diagnosis is made, frequent aortic imaging is indicated, and aneurysmal progression may be especially rapid after aortic dissection, as occurred in our first patient. Staged replacement of affected aortic segments is indicated, sometimes leading to replacement of the entire aorta, as in patient 1. Because the disorder is autosomal dominant with variable clinical expression, genetic counseling and screening of family members is recommended. Total aortic replacement is a major surgical procedure that has carried significant mortality and morbidity in the past. Recent advances in intraoperative management have greatly improved outcomes [3Kouchoukos N.T. Mauney M.C. Masetti P. et al.Single-stage repair of extensive thoracic aortic aneurysms: experience with the arch-first technique and bilateral anterior thoracotomy.J Thorac Cardiovasc Surg. 2004; 128: 669-676PubMed Scopus (73) Google Scholar, 4Kouchoukos N.T. Masetti P. Rokkas C.K. et al.Hypothermic cardiopulmonary bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta.Ann Thorac Surg. 2002; 74: 1885-1887Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar]. Profound hypothermia is ideal for organ protection, not only for the brain but also for the spinal chord and abdominal organs. Continuous perfusion of the cerebral vasculature through axillary artery cannulation during arch replacement has minimized the duration of circulatory arrest, and greatly reduced the incidence of neurologic injury [3Kouchoukos N.T. Mauney M.C. Masetti P. et al.Single-stage repair of extensive thoracic aortic aneurysms: experience with the arch-first technique and bilateral anterior thoracotomy.J Thorac Cardiovasc Surg. 2004; 128: 669-676PubMed Scopus (73) Google Scholar]. Hypothermic protection of the spinal cord, together with routine reimplantation of distal thoracic intercostal/lumbar arteries, has been associated with a low incidence of paraplegia [4Kouchoukos N.T. Masetti P. Rokkas C.K. et al.Hypothermic cardiopulmonary bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta.Ann Thorac Surg. 2002; 74: 1885-1887Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar]. Likewise, hypothermic protection of the kidneys and abdominal viscera has reduced the incidence of organ failure. The clam shell incision has allowed larger segments of aorta to be replaced in a single stage, thus reducing the number of operations required. In summary, LDS is caused by mutations in the TGF-β receptor 1 and 2 genes, and is characterized by progressive aortic aneurysmal disease and dissection. Patients present at an early age and require vigilant monitoring of all vascular segments because of the rapidly progressive nature of the aortic disease. Surgical management using new supportive strategies is likely to produce better long-term outcomes, and total aortic replacement may be necessary.