Mutation-based growth charts for SEDC and other COL2A1 related dysplasias


  • How to cite this article: Terhal PA, van Dommelen P, Le Merrer M, Zankl A, Simon MEH, Smithson SF, Marcelis C, Kerr B, Kinning E, Mansour S, Hennekam RCM, van der Hout AH, Cormier-Daire V, Lund AM, Goodwin L, Mégarbané A, Lees M, Betz RC, Tobias ES, Coucke P, Mortier GR. 2012. Mutation-based growth charts for SEDC and other COL2A1 related dysplasias. Am J Med Genet Part C.


From data collected via a large international collaborative study, we have constructed a growth chart for patients with molecularly confirmed congenital spondylo-epiphyseal dysplasia (SEDC) and other COL2A1 related dysplasias. The growth chart is based on longitudinal height measurements of 79 patients with glycine substitutions in the triple-helical domain of COL2A1. In addition, measurements of 27 patients with other molecular defects, such as arginine to cysteine substitutions, splice mutations, and mutations in the C-terminal propeptide have been plotted on the chart. Height of the patients progressively deviate from that of normal children: compared to normal WHO charts, the mean length/height is −2.6 SD at birth, −4.2 SD at 5 years, and −5.8 SD in adulthood. The mean adult height (male and female combined) of patients with glycine substitutions in the triple-helical region is 138.2 cm but there is a large variation. Patients with glycine to cysteine substitutions tend to cluster within the upper part of the chart, while patients with glycine to serine or valine substitutions are situated between +1 SD and −1 SD. Patients with carboxy-terminal glycine substitutions tend to be shorter than patients with amino-terminal substitutions, while patients with splice mutations are relatively tall. However, there are exceptions and specific mutations can have a strong or a relatively mild negative effect on growth. The observation of significant difference in adult height between affected members of the same family indicates that height remains a multifactorial trait even in the presence of a mutation with a strong dominant effect. © 2012 Wiley Periodicals, Inc.