This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ross, J. L. Articles by Zinn, A. R. Search for Related Content PubMed PubMed Citation Articles by Ross, J. L. Articles by Zinn, A. R.

Phenotypes Associated with SHOX Deficiency

Departments of Pediatrics (J.L.R., C.S., K.K., A.N.) and Orthopedic Surgery (J.A., L.O.), Thomas Jefferson University, Philadelphia, Pennsylvania 19107; Alfred I. DuPont Hospital for Children (J.L.R., C.S.), Wilmington, Delaware 19803; Molecular Endocrinology, Research and Development (P.M.), Esoterix Endocrinology, Calabasas Hills, California 91301; Laboratory Corporation of America (P.P.), Research Triangle Park, North Carolina 27709; Biomedical Computing (H.K.), Philadelphia, Pennsylvania 19115; Texas Scottish Rite Hospital for Children (P.C., M.E.), Dallas, Texas 75219; Department of Pathology (F.E.), The University of Texas Southwestern Medical School, Dallas, Texas 75219; and Eugene McDermott Center for Human Growth and Development and Department of Internal Medicine (F.W., H.C., A.R.Z.), The University of Texas Southwestern Medical School, Dallas, Texas 75390

Address all correspondence and requests for reprints to: Judith L. Ross, M.D., Thomas Jefferson University, Department of Pediatrics, 1025 Walnut Street, Philadelphia, Pennsylvania 19107. E-mail: Judith.Ross@mail.tju.edu (or Andrew.Zinn{at}UTSouthwestern.edu)

Abstract

Leri-Weill dyschondrosteosis (LWD) (MIM 127300) is a dominantly inherited skeletal dysplasia characterized phenotypically by Madelung wrist deformity, mesomelia, and short stature. LWD can now be defined genetically by haploinsufficiency of the SHOX (short stature homeobox-containing) gene. We have studied 21 LWD families (43 affected LWD subjects, including 32 females and 11 males, ages 3–56 yr) with confirmed SHOX abnormalities. We investigated the relationship between SHOX mutations, height deficit, and Madelung deformity to determine the contribution of SHOX haploinsufficiency to the LWD and Turner syndrome (TS) phenotypes. Also, we examined the effects of age, gender, and female puberty (estrogen) on the LWD phenotype.

SHOX deletions were present in affected individuals from 17 families (81%), and point mutations were detected in 4 families (19%). In the LWD subjects, height deficits ranged from -4.6 to +0.6 SD (mean ± SD = -2.2 ± 1.0). There were no statistically significant effects of age, gender, pubertal status, or parental origin of SHOX mutations on height z-score. The height deficit in LWD is approximately two thirds that of TS. Madelung deformity was present in 74% of LWD children and adults and was more frequent and severe in females than males. The prevalence of the Madelung deformity was higher in the LWD vs. a TS population. The prevalence of increased carrying angle, high arched palate, and scoliosis was similar in the two populations.

In conclusion, SHOX deletions or mutations accounted for all of our LWD cases. SHOX haploinsufficiency accounts for most, but not all, of the TS height deficit. The LWD phenotype shows some gender- and age-related differences.

This article has been cited by other articles:

				M. R. Perkiomaki and L. Alvesalo Palatine ridges and tongue position in Turner syndrome subjects Eur J Orthod, April 1, 2008; 30(2): 163 - 168. [Abstract] [Full Text] [PDF]

				A. Marchini, B. Hacker, T. Marttila, V. Hesse, J. Emons, B. Weiss, M. Karperien, and G. Rappold BNP is a transcriptional target of the short stature homeobox gene SHOX Hum. Mol. Genet., December 15, 2007; 16(24): 3081 - 3087. [Abstract] [Full Text] [PDF]

				N. Sabherwal, F. Bangs, R. Roth, B. Weiss, K. Jantz, E. Tiecke, G. K. Hinkel, C. Spaich, B. P. Hauffa, H. van der Kamp, et al. Long-range conserved non-coding SHOX sequences regulate expression in developing chicken limb and are associated with short stature phenotypes in human patients Hum. Mol. Genet., January 15, 2007; 16(2): 210 - 222. [Abstract] [Full Text] [PDF]

				C. A. Bondy and for The Turner Syndrome Consensus Study Group Care of Girls and Women with Turner Syndrome: A Guideline of the Turner Syndrome Study Group J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 10 - 25. [Abstract] [Full Text] [PDF]

				V Cantagrel, A-M Lossi, S Boulanger, D Depetris, M-G Mattei, J Gecz, C E Schwartz, L Van Maldergem, and L Villard Disruption of a new X linked gene highly expressed in brain in a family with two mentally retarded males J. Med. Genet., October 1, 2004; 41(10): 736 - 742. [Abstract] [Full Text] [PDF]

				G. Binder, A. Renz, A. Martinez, A. Keselman, V. Hesse, S. W. Riedl, G. Hausler, S. Fricke-Otto, H. Frisch, J. J. Heinrich, et al. SHOX Haploinsufficiency and Leri-Weill Dyschondrosteosis: Prevalence and Growth Failure in Relation to Mutation, Sex, and Degree of Wrist Deformity J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4403 - 4408. [Abstract] [Full Text] [PDF]

				T Tsilchorozidou, F H Menko, F Lalloo, A Kidd, R De Silva, H Thomas, P Smith, A Malcolmson, J Dore, K Madan, et al. Constitutional rearrangements of chromosome 22 as a cause of neurofibromatosis 2 J. Med. Genet., July 1, 2004; 41(7): 529 - 534. [Full Text] [PDF]

				N Sabherwal, R J Blaschke, A Marchini, D Heine-Suner, J Rosell, J Ferragut, W F Blum, and G Rappold A novel point mutation A170P in the SHOX gene defines impaired nuclear translocation as a molecular cause for Leri-Weill dyschondrosteosis and Langer dysplasia J. Med. Genet., June 1, 2004; 41(6): e83 - e83. [Full Text] [PDF]

				V. K. Bakalov, L. Axelrod, J. Baron, L. Hanton, L. M. Nelson, J. C. Reynolds, S. Hill, J. Troendle, and C. A. Bondy Selective Reduction in Cortical Bone Mineral Density in Turner Syndrome Independent of Ovarian Hormone Deficiency J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5717 - 5722. [Abstract] [Full Text] [PDF]

				G. Binder, M. B. Ranke, and D. D. Martin Auxology Is a Valuable Instrument for the Clinical Diagnosis of SHOX Haploinsufficiency in School-Age Children with Unexplained Short Stature J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4891 - 4896. [Abstract] [Full Text] [PDF]

				M. Roubicek, M. C. Arriazu, and G. Isaac SHOX Deficiency Phenotypes J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 4004 - 4004. [Full Text]

				R. G. Rosenfeld Author's Response: SHOX--A Geneticist's View J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1912 - 1912. [Full Text] [PDF]

				G. Rappold SHOX: A Geneticist's View J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1911 - 1912. [Full Text] [PDF]

				R. G. Rosenfeld EDITORIAL: A SHOX to the System J. Clin. Endocrinol. Metab., December 1, 2001; 86(12): 5672 - 5673. [Full Text] [PDF]