A study of the clinical and radiological features in a cohort of 93 patients with a COL2A1 mutation causing spondyloepiphyseal dysplasia congenita or a related phenotype

Paulien A Terhal, Rutger Jan A J Nievelstein, Eva J J Verver, Vedat Topsakal, Paula van Dommelen, Kristien Hoornaert, Martine Le Merrer, Andreas Zankl, Marleen E H Simon, Sarah F Smithson, Carlo Marcelis, Bronwyn Kerr, Jill Clayton-Smith, Esther Kinning, Sahar Mansour, Frances Elmslie, Linda Goodwin, Annemarie H van der Hout, Hermine E Veenstra-Knol, Johanna C HerkertAllan M Lund, Raoul C M Hennekam, André Mégarbané, Melissa M Lees, Louise C Wilson, Alison Male, Jane Hurst, Yasemin Alanay, Göran Annerén, Regina C Betz, Ernie M H F Bongers, Valerie Cormier-Daire, Anne Dieux, Albert David, Mariet W Elting, Jenneke van den Ende, Andrew Green, Johanna M van Hagen, Niels Thomas Hertel, Muriel Holder-Espinasse, Nicolette den Hollander, Tessa Homfray, Hanne D Hove, Susan Price, Annick Raas-Rothschild, Marianne Rohrbach, Barbara Schroeter, Mohnish Suri, Elizabeth M Thompson, Edward S Tobias, Annick Toutain, Maaike Vreeburg, Emma Wakeling, Nine V Knoers, Paul Coucke, Geert R Mortier

69 Citationer (Scopus)


Type 2 collagen disorders encompass a diverse group of skeletal dysplasias that are commonly associated with orthopedic, ocular, and hearing problems. However, the frequency of many clinical features has never been determined. We retrospectively investigated the clinical, radiological, and genotypic data in a group of 93 patients with molecularly confirmed SEDC or a related disorder. The majority of the patients (80/93) had short stature, with radiological features of SEDC (n = 64), others having SEMD (n = 5), Kniest dysplasia (n = 7), spondyloperipheral dysplasia (n = 2), or Torrance-like dysplasia (n = 2). The remaining 13 patients had normal stature with mild SED, Stickler-like syndrome or multiple epiphyseal dysplasia. Over 50% of the patients had undergone orthopedic surgery, usually for scoliosis, femoral osteotomy or hip replacement. Odontoid hypoplasia was present in 56% (95% CI 38-74) and a correlation between odontoid hypoplasia and short stature was observed. Atlanto-axial instability, was observed in 5 of the 18 patients (28%, 95% CI 10-54) in whom flexion-extension films of the cervical spine were available; however, it was rarely accompanied by myelopathy. Myopia was found in 45% (95% CI 35-56), and retinal detachment had occurred in 12% (95% CI 6-21; median age 14 years; youngest age 3.5 years). Thirty-two patients complained of hearing loss (37%, 95% CI 27-48) of whom 17 required hearing aids. The ophthalmological features and possibly also hearing loss are often relatively frequent and severe in patients with splicing mutations. Based on clinical findings, age at onset and genotype-phenotype correlations in this cohort, we propose guidelines for the management and follow-up in this group of disorders. © 2015 Wiley Periodicals, Inc.

TidsskriftAmerican Journal of Medical Genetics. Part A
Udgave nummer3
Sider (fra-til)461-75
Antal sider15
StatusUdgivet - mar. 2015


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