How to cite this article: Simon M, Campos-Xavier AB, Mittaz-Crettol L, Valadares ER, Carvalho D, Speck-Martins CE, Nampoothiri S, Alanay Y, Mihci E, van Bever Y, Garcia-Segarra N, Cavalcanti D, Mortier G, Bonafé L, Superti-Furga A. 2012. Severe neurologic manifestations from cervical spine instability in spondylo-megaepiphyseal-metaphyseal dysplasia. Am J Med Genet Part C Semin Med Genet.
Severe neurologic manifestations from cervical spine instability in spondylo-megaepiphyseal-metaphyseal dysplasia†
Article first published online: 12 JUL 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part C: Seminars in Medical Genetics
Special Issue: New Topics in the Skeletal Dysplasias
Volume 160C, Issue 3, pages 230–237, 15 August 2012
How to Cite
Simon, M., Campos-Xavier, A. B., Mittaz-Crettol, L., Valadares, E. R., Carvalho, D., Speck-Martins, C. E., Nampoothiri, S., Alanay, Y., Mihci, E., van Bever, Y., Garcia-Segarra, N., Cavalcanti, D., Mortier, G., Bonafé, L. and Superti-Furga, A. (2012), Severe neurologic manifestations from cervical spine instability in spondylo-megaepiphyseal-metaphyseal dysplasia. Am. J. Med. Genet., 160C: 230–237. doi: 10.1002/ajmg.c.31339
- Issue published online: 19 JUL 2012
- Article first published online: 12 JUL 2012
- Brazil-Switzerland Joint Research Project. Grant Number: BSJRP 2012–2014
- Leenaards Foundation
- Faculté de Biologie et Medicine (FBM) of the Lausanne University
- spondylo-megaepiphyseal-metaphyseal dysplasia;
Spondylo-megaepiphyseal-metaphyseal dysplasia (SMMD; OMIM 613330) is a dysostosis/dysplasia caused by recessive mutations in the homeobox-containing gene, NKX3-2 (formerly known as BAPX1). Because of the rarity of the condition, its diagnostic features and natural course are not well known. We describe clinical and radiographic findings in six patients (five of which with homozygous mutations in the NKX3-2 gene) and highlight the unusual and severe changes in the cervical spine and the neurologic complications. In individuals with SMMD, the trunk and the neck are short, while the limbs, fingers and toes are disproportionately long. Radiographs show a severe ossification delay of the vertebral bodies with sagittal and coronal clefts, missing ossification of the pubic bones, large round “balloon-like” epiphyses of the long bones, and presence of multiple pseudoepiphyses at all metacarpals and phalanges. Reduced or absent ossification of the cervical vertebrae leads to cervical instability with anterior or posterior kinking of the cervical spine (swan neck-like deformity, kyknodysostosis). As a result of the cervical spine instability or deformation, five of six patients in our series suffered cervical cord injury that manifested clinically as limb spasticity. Although the number of individuals observed is small, the high incidence of cervical spine deformation in SMMD is unique among skeletal dysplasias. Early diagnosis of SMMD by recognition of the radiographic pattern might prevent of the neurologic complications via prophylactic cervical spine stabilization. © 2012 Wiley Periodicals, Inc.