Prevalence of scoliosis in Williams-Beuren syndrome patients treated at a regional reference center

CLINICAL SCIENCE Prevalence of scoliosis in Williams-Beuren syndrome patients treated at a regional reference center Marcelo Loquette Damasceno,I* Alexandre Fogaça Cristante,II Raphael Martus Marcon,II Tarcı́sio Eloy Pessoa de Barros FilhoIII I Hospital das Clı́nicas da Faculdade de Medicina da Universidade de São Paulo (IOT-HCFMUSP), Department of Orthopaedics and Traumatology, Spine Surgery Division, São Paulo/SP, Brazil. II Hospital das Clı́nicas da Faculdade de Medicina da Universidade de São Paulo (IOT-HCFMUSP), Instituto de Ortopedia e Traumatologia, Spine Division, São Paulo/SP, Brazil. III Hospital das Clı́nicas da Faculdade de Medicina da Universidade de São Paulo (IOTHCFMUSP), Instituto de Ortopedia e Traumatologia, Departamento de Ortopedia e Traumatologia, Disciplina de Ortopedia Geral, Grupo de Oncologia Ortopédica, São Paulo/SP, Brazil. OBJECTIVE: This study assessed the prevalence of scoliosis and the patterns of scoliotic curves in patients with Williams-Beuren syndrome. Williams-Beuren syndrome is caused by a chromosome 7q11.23 deletion in a region containing 28 genes, with the gene encoding elastin situated approximately at the midpoint of the deletion. Mutation of the elastin gene leads to phenotypic changes in patients, including neurodevelopmental impairment of varying degrees, characteristic facies, cardiovascular abnormalities, hypercalcemia, urological dysfunctions, and bone and joint dysfunctions. METHODS: A total of 41 patients diagnosed with Williams-Beuren syndrome, who were followed up at the genetics ambulatory center of a large referral hospital, were included in the study. There were 25 male subjects. The patients were examined and submitted to radiographic investigation for Cobb angle calculation. RESULTS: It was observed that 14 patients had scoliosis; of these 14 patients, 10 were male. The pattern of deformity in younger patients was that of flexible and simple curves, although adults presented with double and triple curves. Statistical analysis showed no relationships between scoliosis and age or sex. CONCLUSION: This study revealed a prevalence of scoliosis in patients with Williams-Beuren syndrome of 34.1%; however, age and sex were not significantly associated with scoliosis or with the severity of the curves. KEYWORDS: Elastin; Scoliosis; Williams-Beuren Syndrome. Damasceno ML, Cristante AF, Marcon RM, Barros Filho TE. Prevalence of scoliosis in Williams-Beuren syndrome patients treated at a regional reference center. Clinics. 2014;69(7):452-456. Received for publication on December 3, 2013; First review completed on December 20, 2013; Accepted for publication on December 20, 2013 E-mail: *corresponding author Tel.: 55 92 98233-9696 (5-7). WBS is caused by a chromosome 7q11.23 deletion in a region containing 28 genes and the gene encoding elastin is situated approximately at the midpoint of this deletion (8-10). Mutation of the elastin gene results in various phenotypic changes, including neurodevelopmental impairment of varying degrees, cardiovascular abnormalities, hypercalcemia, urological dysfunction, and bone and joint dysfunctions (11-13). Elastin is the best-known protein encoded in scoliosis. As the main component of the tissue extracellular matrix, elastin is fundamental to regulating the distribution of elastic fibers in the intervertebral discs. In patients with scoliosis, disorganization of collagen and elastic fibers is observed, elastic fibers are sparse, and the lamellar structure is lost (14-16). Few cases of scoliosis have been reported in patients with WBS (17-19), and the descriptions of the deformities have been brief. The prevalence of scoliosis in WBS is not fully understood, and the patterns of the scoliosis curves in patients with WBS have not been studied. & INTRODUCTION Many studies have identified mutations in the genetic loci encoding proteins that are components of elastic fibers, leading to a wide range of connective tissue disorders, including skeletal, cardiovascular and ocular abnormalities, as well as neurodevelopmental deficits (1-4). One of the most striking aspects of the syndromes that cause musculoskeletal impairment is scoliosis, which occurs frequently in individuals in the same family. Williams-Beuren syndrome (WBS) is a relatively rare disease, with a frequency of 157,500 to 1520,000 living births Copyright ß 2014 CLINICS – This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. No potential conflict of interest was reported. DOI: 10.6061/clinics/2014(07)02 452 CLINICS 2014;69(7):452-456 Scoliosis in Williams-Beuren syndrome patients Damasceno ML et al. The objectives of the present study were to assess the prevalence of scoliosis in patients with WBS and to determine the association of WBS with the patterns of scoliotic curves. observing the alignment of the spine and shoulders and the hip flexibility, in addition to verifying the spinal deviation. When scoliosis was suspected, the examiner verified the pattern of the primary curve, alignment, and sagittal balance. The Cobb angle was calculated, according to the Scoliosis Research Society criteria and was recorded. Scoliosis was defined as a Cobb angle greater than 10 ˚ between the cranial and caudal vertebrae of the spinal curve. The average distance between the two measurements was calculated and used to estimate the prevalence of scoliosis in this study. & MATERIALS AND METHODS Study design and study population The participants in this observational, cross-sectional study were WBS patients undergoing follow-up at the Genetics Ambulatory clinic of our public university hospital. Hospital das Clı́nicas is a referral center for genetic diseases that receives patients from other primary and tertiary health centers from all over Brazil. The patients are regularly followed up free of charge within the Brazilian public health system (Sistema Único de Saúde, SUS). WBS patients present with many different comorbidities of the disease, and in our hospital, they are closely monitored by our multidisciplinary team. For this study, the Genetics Ambulatory clinic provided a list of all of the patients with WBS who were registered at any time for diagnosis or treatment at the institution. The database of the Brazilian Association of Williams-Beuren Syndrome was checked, and 51 patients registered in Brazil were found. Of these patients, 50 were undergoing followup at Hospital das Clı́nicas. After obtaining approval from the local ethics committee, telephone calls were made by the Spinal Surgery Division of the Orthopaedics and Traumatology Department of the same hospital from June to July 2010 to each of the 50 patients registered with the hospital. The patients were asked to v (...truncated)