Clinical features and genetic analysis of Korean patients with Loeys–Dietz syndrome

Abstract

Loeys-Dietz syndrome (LDS) is an inherited disorder that is characterized by the triad of arterial tortuosity and aneurysms, hypertelorism and a bifid uvula or cleft palate. The disease is caused by heterozygous mutations in the genes encoding transforming growth factor b receptors 1 and 2 (TGFBR1 and TGFBR2, respectively). However, studies of patients with LDS are limited in Korea. From June 2000 to December 2010, 13 patients (10 probands) diagnosed with LDS were enrolled. The multidisciplinary data of the patients were reviewed retrospectively. The frequency of each clinical manifestation in Korean patients with LDS was compared with Western populations as described in the report by Loeys et al. Twelve (92%) of the 13 LDS patients had arterial tortuosity, 9 (69%) patients had hypertelorism and 11 (85%) patients had bifid uvula or cleft palate. Mutations in either TGFBR1 or TGFBR2 were detected in nine probands (90%). Of the mutations, five novel mutations were detected; three in TGFBR2 and two in TGFBR1. Blue sclera and atrial septal defect were not observed in the Korean patients, and the frequency of blue sclera was significantly lower in our Korean population than previously-described Western population (0 vs 40%; P¼0.005). Despite the restricted number of patients in our study, we identified five novel mutations in the TGFBR1 and TGFBR2 genes and, except for blue sclera, no differences in phenotype are apparent between Korean patients and Western patients. Keywords: arterial tortuosity; bifid uvula; hypertelorism; Loeys-Dietz syndrome; transforming growth factor b receptors INTRODUCTION Loeys-Dietz syndrome (LDS), a genetic disorder affecting the connective tissue, is caused by mutations in the genes encoding transforming growth factor b receptors 1 and 2 (TGFBR1 and TGFBR2, respectively). 1 LDS is characterized by the triad of hypertelorism, a bifid uvula or cleft palate and generalized arterial tortuosity with widespread vascular aneurysm and dissection. 2 The diagnosis of LDS is made according to clinical presentations in the proband and family members, and molecular genetic testing of the TGFBR1 and TGFBR2 genes. 3 Early and accurate diagnosis is essential to patients with LDS because they are at increased risk for aortic dissection or rupture at an early age. To date, most studies related to LDS are based on data obtained from the European and American populations. There are few data regarding the clinical and genetic characteristics of the Korean patients with LDS, leaving doubt as to whether or not there are racial differences in the physical presentation of LDS between the Oriental and Western populations.Therefore, we investigated the clinical and genetic characteristics in the Korean patients with LDS, and compared clinical manifestations between Korean patients and Western populations as reported by Loeys et al. 2 MATERIALS AND METHODS SubjectsWe reviewed 22 consecutive patients who were suspicious of having LDS from June 2000 to December 2010. All had undergone genetic analysis of the TGFBR1 an...

Evaluation of cervical spine pathology in children with Loeys-Dietz syndrome

“…Cervical spine instability in patients with LDS is reported widely in the literature,[ 5 , 7 , 16 , 23 , 25 , 26 ] therefore, evaluation is an important surveillance tool to identify potentially serious pathology and monitor for progression. We identified a 37.5% prevalence of cervical instability among those evaluated in our series.…”

“…The frequency of cervical spine instability in LDS patients is poorly described in the literature, with a prevalence ranging from 16.3% to 100%. [ 5 , 7 , 16 , 23 , 25 , 26 ] Due to rarity of disease, understanding of disease pathology is continually evolving, reflected by the recent development of cervical spine screening recommendations for these patients. Therefore, we aimed to examine our experience with cervical spine evaluation in patients with LDS at a tertiary academic referral center.…”

Aortic Aneurysm in Children and Adolescents

“…Elective surgery is recommended at an aortic root diameter of 40 mm. In Loeys-Dietz syndrome, defective microfibrils due to excessive activity of Transforming Growth Factor β activity lead to defective formation of matrix in the arterial wall and thus, aortic aneurysms [24,25,26].…”