Background LDS is a rare connective tissue disease with significant phenotypic overlap with Marfan syndrome(MFS) and characterized by generalized arterial tortuosity, craniofacial features(hypertelorism, bifid uvula, cleft palate) and aggressive aortic aneurysm disease. Whereas MFS results from mutations in fibrillin 1(FBN1) gene, LDS is caused by mutations in transforming growth factor �� receptors 1 and 2(TGFBR1 and 2) genes. Previously, we reported the first LDS case in Korea. Now, we are reporting nine LDS patients with two LDS families, which are the first familial LDS in Korea. Method and result We thoroughly examined and investigated mutations of TGFBR gene in 12 patients who were suspected of LDS. They were children with aggressive aortic aneurysms and adult patients initially diagnosed as MFS or Ehlers-Danlos syndrome IV without mutations in FBN1 or procollagen type 3 (COL3A1). Among these 12 patients, 6 patients (M:F=4:2) were identified as LDS. Genetic analysis revealed TGFBR mutations in five patients(1 patient: mutation in TGFBR1 and 4 patients: mutation in TGFBR2). Molecular study of family members identified two patients with positive family members. One patient���s mother, and the other patient���s daughter and sun were affected. Involvement of aorta was observed in all proband cases; annuloaortic ectasia in 4 patients, aortic regurgitation in 3 patients, and type I aortic dissection in 2 patients. Five of these patients underwent operative repair; valve-sparing root replacement in 2 patients, Bentall procedure in 2 patients, and descending thoracic aorta replacement in 1 patient. Six patients had other cardiac anomalies; 2 patients: PDA, 2 patients: MVP, 2 patients: pulmonary artery aneurysm. Arterial tortuosity was noticed in 43% of patients. All of these patients had bifid uvula and/or cleft palate. Hypertelorism was noted in 57% of patients. Skeletal deformities were observed in 100% of patients. Conclusion Because LDS shows more extensive and aggressive disease course, it is crucial to recognize early and manage properly. For early recognition of this disease, high degree of suspicion is mandatory and genetic testing of TGFBRs should be performed in suspected cases.