Search tips
Search criteria 


Logo of jmedgeneJournal of Medical GeneticsVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
J Med Genet. 1996 September; 33(9): 749–752.
PMCID: PMC1050728

Clinical and genetic heterogeneity of hypochondroplasia.


Hypochondroplasia (HCH) is an autosomal dominant condition characterised by short stature, micromelia, and lumbar lordosis. In a series of 29 HCH probands (13 sporadic cases, 16 familial cases), we tested their DNA for the N540K recurrent mutation previously described in the proximal tyrosine kinase domain of the FGFR3 gene on chromosome 4p16.3, and we detected this mutation in 21/29 HCH patients. Interestingly, three familial cases were clearly unlinked to chromosome 4p16.3. Reviewing the clinical and radiological manifestations of the disease a posteriori, we observed that the N540K mutation was associated with relative macrocrania with a high and large forehead and short hands. By contrast, in the three pedigrees inconsistent with linkage to chromosome 4p16.3, the clinical phenotype was milder, macrocephaly and shortening of the long bones was less obvious, the hands were normal, and no metaphyseal flaring was noted. This study supports the view that HCH is a clinically and genetically heterogeneous condition.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Maroteaux P, Falzon P. Hypochondroplasie. Revue de 80 cas. Arch Fr Pediatr. 1988 Feb;45(2):105–109. [PubMed]
  • Wynne-Davies R, Walsh WK, Gormley J. Achondroplasia and hypochondroplasia. Clinical variation and spinal stenosis. J Bone Joint Surg Br. 1981;63B(4):508–515. [PubMed]
  • Hall BD, Spranger J. Hypochondroplasia: clinical and radiological aspects in 39 cases. Radiology. 1979 Oct;133(1):95–100. [PubMed]
  • McKusick VA, Kelly TE, Dorst JP. Observations suggesting allelism of the achondroplasia and hypochondroplasia genes. J Med Genet. 1973 Mar;10(1):11–16. [PMC free article] [PubMed]
  • Velinov M, Slaugenhaupt SA, Stoilov I, Scott CI, Jr, Gusella JF, Tsipouras P. The gene for achondroplasia maps to the telomeric region of chromosome 4p. Nat Genet. 1994 Mar;6(3):314–317. [PubMed]
  • Le Merrer M, Rousseau F, Legeai-Mallet L, Landais JC, Pelet A, Bonaventure J, Sanak M, Weissenbach J, Stoll C, Munnich A, et al. A gene for achondroplasia-hypochondroplasia maps to chromosome 4p. Nat Genet. 1994 Mar;6(3):318–321. [PubMed]
  • Rousseau F, Bonaventure J, Legeai-Mallet L, Pelet A, Rozet JM, Maroteaux P, Le Merrer M, Munnich A. Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia. Nature. 1994 Sep 15;371(6494):252–254. [PubMed]
  • Shiang R, Thompson LM, Zhu YZ, Church DM, Fielder TJ, Bocian M, Winokur ST, Wasmuth JJ. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell. 1994 Jul 29;78(2):335–342. [PubMed]
  • Bellus GA, Hefferon TW, Ortiz de Luna RI, Hecht JT, Horton WA, Machado M, Kaitila I, McIntosh I, Francomano CA. Achondroplasia is defined by recurrent G380R mutations of FGFR3. Am J Hum Genet. 1995 Feb;56(2):368–373. [PubMed]
  • Hecht JT, Herrera CA, Greenhaw GA, Francomano CA, Bellus GA, Blanton SH. Confirmatory linkage of hypochondroplasia to chromosome arm 4p. Am J Med Genet. 1995 Jul 3;57(3):505–506. [PubMed]
  • Bellus GA, McIntosh I, Smith EA, Aylsworth AS, Kaitila I, Horton WA, Greenhaw GA, Hecht JT, Francomano CA. A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia. Nat Genet. 1995 Jul;10(3):357–359. [PubMed]
  • Prinos P, Costa T, Sommer A, Kilpatrick MW, Tsipouras P. A common FGFR3 gene mutation in hypochondroplasia. Hum Mol Genet. 1995 Nov;4(11):2097–2101. [PubMed]
  • Stoilov I, Kilpatrick MW, Tsipouras P, Costa T. Possible genetic heterogeneity in hypochondroplasia. J Med Genet. 1995 Jun;32(6):492–493. [PMC free article] [PubMed]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Group