CLINICAL REPORT A New Form of Severe Spondyloepimetaphyseal Dysplasia: Clinical and Radiological Characterization † Bertrand Isidor, 1,2 * Loı ¨c Geffroy, 3 Benoı ˆt de Courtivron, 4 Ce ´dric Le Caignec, 1 Christian T. Thiel, 5 Geert Mortier, 6 Vale ´rie Cormier-Daire, 7 Albert David, 1 and Annick Toutain 8 1 Service de Ge ´ne ´tique Me ´dicale, CHU de Nantes, Nantes, France 2 INSERM, UMR-S 957, Nantes, France 3 Service d’Orthope ´die Pe ´diatrique, CHU de Nantes, Nantes, France 4 Service de Chirurgie Orthope ´dique Pe ´diatrique, CHU de Tours, Tours, France 5 Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen, Germany 6 Department of Medical Genetics, Antwerp University Hospital and University of Antwerp, Edegem, Belgium 7 De ´partement de Ge ´ne ´tique, Ho ˆpital Necker-Enfants Malades, Paris, France 8 Service de Ge ´ne ´tique, Centre Hospitalier Universitaire, Tours, France Manuscript Received: 9 October 2012; Manuscript Accepted: 30 May 2013 We report on two patients with a severe form of spondyloepi- metaphyseal dysplasia (SEMD). Both patients show normal birth length, early postnatal growth deficiency, severe short stature, flexion contractures in the hips, bowing of the legs with genu varum. Skeletal radiographies show platyspondyly and charac- teristic vertebral body shape with central indentation of end- plates, progressive, and severe metaphyseal changes, very small and irregular proximal femoral epiphyses with severe coxa vara, absence of calcifications, and mild metaphyseal irregularities in upper limbs. The similarities in the skeletal radiographs with SEMD type Strudwick and SEMD matrilin 3 type prompted us to analyze the COL2A1 and MATN3 genes. Direct sequencing of genomic DNA failed to identify any mutation in COL2A1 for both patients and MATN3 sequencing for Patient 1 identified only one heterozy- gous variant with no predicted damaging effect inherited from an unaffected parent. We therefore conclude that this form of SEMD probably differs from SEMD matrilin 3 type and does not belong to the spectrum of type II collagenopathies. The similarities between our two patients allowed us to propose that they might show a new form of SEMD. Ó 2013 Wiley Periodicals, Inc. Key words: spondyloepimetaphyseal dysplasia; platyspondyly; skeletal dysplasia; COL2A1; MATN3 INTRODUCTION The last Nosology of Constitutional Bone Disorders [Warman et al., 2011] distinguished 15 different forms of Spondyloepime- taphyseal dysplasias (SEMD). All are defined by the combination of vertebral, epiphyseal, and metaphyseal abnormalities. The diagnosis is either based on the specificity of the skeletal manifes- tations or on the presence of characteristic extraskeletal features, which may appear during the course of the disease. Most of SEMD are rare and often arise sporadically, but distinctive genetic forms with autosomal dominant, autosomal recessive, or X-linked transmission have been reported. Here, we report on two unrelated patients with severe vertebral and epimetaphyseal abnormalities distinct from previous reported SEMD. How to Cite this Article: Isidor B, Geffroy L, de Courtivron B, Le Caignec C, Thiel CT, Mortier G, Cormier- Daire V, David A, Toutain A. 2013. A new form of severe spondyloepimetaphyseal dysplasia: Clinical and radiological characterization. Am J Med Genet Part A 161A:2645–2651. † This article was published online on 16 Aug 2013. An error was subsequently identified in Fig. 4 and its legend. The corrected Fig. 4 and legend are shown in this article. Ã Corresponding to: Bertrand Isidor, Medical Genetics Unit, Centre Hospitalier Universitaire de Nantes 7, Quai Moncousou, 44000 Nantes Cedex, France. E-mail: bertrand.isidor@chu-nantes.fr Article first published online in Wiley Online Library (wileyonlinelibrary.com): 16 August 2013 DOI 10.1002/ajmg.a.36132 Ó 2013 Wiley Periodicals, Inc. 2645