Abstract
Klippel-Feil Syndrome (KFS) is characterized by congenital vertebral fusion believed to result from faulty segmentation along the embryo's developing axis. KFS appears to be a heterogeneous disease often associated with craniofacial malformation. Here we provide the first evidence of a familial KFS gene locus on 8q, where an inv(8)(q22.2q23.3) has been found segregating with congenital vertebral fusion. The four-generation KF2-01 family present with dominant form of the KFS where the sequence of vertebral fusion was confined to the cervical spine (always including the C2-3 fusion and reduced expression of the C4-5 and C6-7 fusions) in association with malformation of laryngeal cartilages and mild-to-severe vocal impairment.
Full text
PDF![1364](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dabf/1801422/f2a697c37d84/ajhg00038-0111.png)
![1365](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dabf/1801422/e7f656e22066/ajhg00038-0112.png)
![1366](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dabf/1801422/ced6e0689d74/ajhg00038-0113.png)
![1367](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dabf/1801422/c7abebe0d3db/ajhg00038-0114.png)
![1368](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dabf/1801422/14daf1da5f72/ajhg00038-0115.png)
![1369](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dabf/1801422/bc74a5a820e5/ajhg00038-0116.png)
![1370](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dabf/1801422/3c2ea2e2d384/ajhg00038-0117.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ang S. L., Rossant J. Anterior mesendoderm induces mouse Engrailed genes in explant cultures. Development. 1993 May;118(1):139–149. doi: 10.1242/dev.118.1.139. [DOI] [PubMed] [Google Scholar]
- BROWN M. W., TEMPLETON A. W., HODGES F. J., 3rd THE INCIDENCE OF ACQUIRED AND CONGENITAL FUSIONS IN THE CERVICAL SPINE. Am J Roentgenol Radium Ther Nucl Med. 1964 Dec;92:1255–1259. [PubMed] [Google Scholar]
- Clarke R. A., Davis P. J., Tonkin J. Klippel-Feil syndrome associated with malformed larynx. Case report. Ann Otol Rhinol Laryngol. 1994 Mar;103(3):201–207. doi: 10.1177/000348949410300306. [DOI] [PubMed] [Google Scholar]
- Connor J. M., Smith R. The cervical spine in fibrodysplasia ossificans progressiva. Br J Radiol. 1982 Jul;55(655):492–496. doi: 10.1259/0007-1285-55-655-492. [DOI] [PubMed] [Google Scholar]
- Cordes S. P., Barsh G. S. The mouse segmentation gene kr encodes a novel basic domain-leucine zipper transcription factor. Cell. 1994 Dec 16;79(6):1025–1034. doi: 10.1016/0092-8674(94)90033-7. [DOI] [PubMed] [Google Scholar]
- Couly G. F., Coltey P. M., Le Douarin N. M. The triple origin of skull in higher vertebrates: a study in quail-chick chimeras. Development. 1993 Feb;117(2):409–429. doi: 10.1242/dev.117.2.409. [DOI] [PubMed] [Google Scholar]
- Deutsch U., Dressler G. R., Gruss P. Pax 1, a member of a paired box homologous murine gene family, is expressed in segmented structures during development. Cell. 1988 May 20;53(4):617–625. doi: 10.1016/0092-8674(88)90577-6. [DOI] [PubMed] [Google Scholar]
- Gunderson C. H., Greenspan R. H., Glaser G. H., Lubs H. A. The Klippel-Feil syndrome: genetic and clinical reevaluation of cervical fusion. Medicine (Baltimore) 1967 Nov;46(6):491–512. doi: 10.1097/00005792-196711000-00003. [DOI] [PubMed] [Google Scholar]
- Hunt P., Gulisano M., Cook M., Sham M. H., Faiella A., Wilkinson D., Boncinelli E., Krumlauf R. A distinct Hox code for the branchial region of the vertebrate head. Nature. 1991 Oct 31;353(6347):861–864. doi: 10.1038/353861a0. [DOI] [PubMed] [Google Scholar]
- Hunt P., Krumlauf R. Deciphering the Hox code: clues to patterning branchial regions of the head. Cell. 1991 Sep 20;66(6):1075–1078. doi: 10.1016/0092-8674(91)90029-x. [DOI] [PubMed] [Google Scholar]
- Kessel M., Gruss P. Homeotic transformations of murine vertebrae and concomitant alteration of Hox codes induced by retinoic acid. Cell. 1991 Oct 4;67(1):89–104. doi: 10.1016/0092-8674(91)90574-i. [DOI] [PubMed] [Google Scholar]
- Lowry R. B. The Klippel-Feil anomalad as part of the fetal alcohol syndrome. Teratology. 1977 Aug;16(1):53–56. doi: 10.1002/tera.1420160109. [DOI] [PubMed] [Google Scholar]
- Lüdecke H. J., Wagner M. J., Nardmann J., La Pillo B., Parrish J. E., Willems P. J., Haan E. A., Frydman M., Hamers G. J., Wells D. E. Molecular dissection of a contiguous gene syndrome: localization of the genes involved in the Langer-Giedion syndrome. Hum Mol Genet. 1995 Jan;4(1):31–36. doi: 10.1093/hmg/4.1.31. [DOI] [PubMed] [Google Scholar]
- MARTEL W., HOLT J. F., CASSIDY J. T. Roentgenologic manifestations of juvenile rheumatoid arthritis. Am J Roentgenol Radium Ther Nucl Med. 1962 Sep;88:400–423. [PubMed] [Google Scholar]
- McBride W. Z. Klippel-Feil syndrome. Am Fam Physician. 1992 Feb;45(2):633–635. [PubMed] [Google Scholar]
- McGinnis W., Krumlauf R. Homeobox genes and axial patterning. Cell. 1992 Jan 24;68(2):283–302. doi: 10.1016/0092-8674(92)90471-n. [DOI] [PubMed] [Google Scholar]
- Morgan M. K., Onofrio B. M., Bender C. E. Familial os odontoideum. Case report. J Neurosurg. 1989 Apr;70(4):636–639. doi: 10.3171/jns.1989.70.4.0636. [DOI] [PubMed] [Google Scholar]
- Nguyen V. D., Tyrrel R. Klippel-Feil syndrome: patterns of bony fusion and wasp-waist sign. Skeletal Radiol. 1993 Oct;22(7):519–523. doi: 10.1007/BF00209100. [DOI] [PubMed] [Google Scholar]
- Stern C. D., Keynes R. J. Spatial patterns of homeobox gene expression in the developing mammalian CNS. Trends Neurosci. 1988 May;11(5):190–192. doi: 10.1016/0166-2236(88)90120-8. [DOI] [PubMed] [Google Scholar]
- Tommerup N. Mendelian cytogenetics. Chromosome rearrangements associated with mendelian disorders. J Med Genet. 1993 Sep;30(9):713–727. doi: 10.1136/jmg.30.9.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tucker J. A., Tucker G. F. Some aspects of fetal laryngeal development. Ann Otol Rhinol Laryngol. 1975 Jan-Feb;84(1 Pt 1):49–55. doi: 10.1177/000348947508400108. [DOI] [PubMed] [Google Scholar]
- Wood S., Ben Othmane K., Bergerheim U. S., Blanton S. H., Bookstein R., Clarke R. A., Daiger S. P., Donis-Keller H., Drayna D., Kumar S. Report and abstracts of the First International Workshop on Human Chromosome 8 Mapping. Vancouver, British Columbia, May 2-4, 1993. Cytogenet Cell Genet. 1993;64(3-4):134–146. [PubMed] [Google Scholar]