How to Cite this Article: de Munnik SA, Otten BJ, Schoots J, Bicknell LS, Aftimos S, Al-Aama JY, van Bever Y, Bober MB, Borm GF, Clayton-Smith J, Deal CL, Edrees AY, Feingold M, Fryer A, van Hagen JM, Hennekam RC, Jansweijer MCE, Johnson D, Kant SG, Opitz JM, Ramadevi AR, Reardon W, Ross A, Sarda P, Schrander-Stumpel CTRM, Sluiter AE, Temple IK, Terhal PA, Toutain A, Wise CA, Wright M, Skidmore DL, Samuels ME, Hoefsloot LH, Knoers NVAM, Brunner HG, Jackson AP, Bongers EMHF. 2012. Meier–Gorlin syndrome: Growth and secondary sexual development of a microcephalic primordial dwarfism disorder. Am J Med Genet Part A 158A: 2733–2742.
Meier–Gorlin syndrome: Growth and secondary sexual development of a microcephalic primordial dwarfism disorder†
Article first published online: 28 SEP 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Special Issue: SPECIAL ISSUE: GROWTH CHARTS IN GENETIC SYNDROMES
Volume 158A, Issue 11, pages 2733–2742, November 2012
How to Cite
de Munnik, S. A., Otten, B. J., Schoots, J., Bicknell, L. S., Aftimos, S., Al-Aama, J. Y., van Bever, Y., Bober, M. B., Borm, G. F., Clayton-Smith, J., Deal, C. L., Edrees, A. Y., Feingold, M., Fryer, A., van Hagen, J. M., Hennekam, R. C., Jansweijer, M. C.E., Johnson, D., Kant, S. G., Opitz, J. M., Ramadevi, A. R., Reardon, W., Ross, A., Sarda, P., Schrander-Stumpel, C. T.R.M., Sluiter, A. E., Temple, I. K., Terhal, P. A., Toutain, A., Wise, C. A., Wright, M., Skidmore, D. L., Samuels, M. E., Hoefsloot, L. H., Knoers, N. V.A.M., Brunner, H. G., Jackson, A. P. and Bongers, E. M.H.F. (2012), Meier–Gorlin syndrome: Growth and secondary sexual development of a microcephalic primordial dwarfism disorder. Am. J. Med. Genet., 158A: 2733–2742. doi: 10.1002/ajmg.a.35681
- Issue published online: 17 OCT 2012
- Article first published online: 28 SEP 2012
- Manuscript Accepted: 3 SEP 2012
- Manuscript Received: 30 NOV 2011
- MRC and Lister Institute for Preventative Medicine
- Meier–Gorlin syndrome;
- ear-patella-short stature;
- growth hormone therapy;
- abnormal secondary sexual development;
- genital underdevelopment
Meier–Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by primordial dwarfism, microtia, and patellar aplasia/hypoplasia. Recently, mutations in the ORC1, ORC4, ORC6, CDT1, and CDC6 genes, encoding components of the pre-replication complex, have been identified. This complex is essential for DNA replication and therefore mutations are expected to impair cell proliferation and consequently could globally reduce growth. However, detailed growth characteristics of MGS patients have not been reported, and so this is addressed here through study of 45 MGS patients, the largest cohort worldwide. Here, we report that growth velocity (length) is impaired in MGS during pregnancy and first year of life, but, thereafter, height increases in paralleled normal reference centiles, resulting in a mean adult height of −4.5 standard deviations (SD). Height is dependent on ethnic background and underlying molecular cause, with ORC1 and ORC4 mutations causing more severe short stature and microcephaly. Growth hormone therapy (n = 9) was generally ineffective, though in two patients with significantly reduced IGF1 levels, growth was substantially improved by GH treatment, with 2SD and 3.8 SD improvement in height. Growth parameters for monitoring growth in future MGS patients are provided and as well we highlight that growth is disproportionately affected in certain structures, with growth related minor genital abnormalities (42%) and mammary hypoplasia (100%) frequently present, in addition to established effects on ears and patellar growth. © 2012 Wiley Periodicals, Inc.