Craniosynostosis suggestive of Saethre-Chotzen syndrome: Clinical description of a large kindred and exclusion of candidate regions on 7p

Gernet, Steven von; Schuffenhauer, Simone; Golla, Astrid; Lichtner, Peter; Balg, Stefanie; Mühlbauer, W.; Murken, Jan; Fairley, Jeffrey; Meitinger, Thomas

doi:10.1002/(sici)1096-8628(19960503)63:1<177::aid-ajmg31>3.0.co;2-j

Cited by 14 publications

(3 citation statements)

References 24 publications

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“…Family members are numbered according to a previous report. 13 Abteilung fiir Medizinische Genetik der Kinderpol;klinik, Ludwig-Ma--milians-Universitat, Goethestrasse 29, 80336 Muinchen, Germany A Golla P Lichtner J Murken S Schuffenhauer Figure 2 Affected subject IV.9 (family 1) with unilateral coronal craniosynostosi age of 3 months. Note markedfacial asymmetry and domed forehead with relative frontal hairline.…”

Section: Introductionmentioning

confidence: 99%

Phenotypic expression of the fibroblast growth factor receptor 3 (FGFR3) mutation P250R in a large craniosynostosis family.

Golla

Lichmer

Gernet

et al. 1997

Journal of Medical Genetics

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The craniosynostosis syndromes are a heterogeneous group of sporadic, autosomal dominant disorders with significant clinical overlap. Recently, we described a large family with autosomal dominant craniosynostosis suggestive of SaethreChotzen syndrome, in which linkage to the Saethre-Chotzen syndrome loci on 7p had been excluded.We now report the presence of a mutation in the fibroblast growth factor receptor 3 (FGFR3) in this family. The mutation, P250R, had been previously reported in 10 patients with non-syndromic craniosynostosis. Variable expression of this mutation is evident especially in two additional members of this family, one of whom is severely affected with pancraniosynostosis. The family provides a further example of genetic heterogeneity and variable expression of the craniosynostosis syndromes and broadens the phenotypic spectrum associated with the FGFR3 mutation P250R. In addition, we found a polymorphism (F384L) in the transmembrane domain of FGFR3 which occurs with a frequency of 3% in the Turkish population but is uncommon among Germans.

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Section: Introductionmentioning

confidence: 99%

Phenotypic expression of the fibroblast growth factor receptor 3 (FGFR3) mutation P250R in a large craniosynostosis family.

Golla

Lichmer

Gernet

et al. 1997

Journal of Medical Genetics

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“…After discovery of linkage to 4p16, this disorder was designated Adelaide-type craniosynostosis, and the associated coneshaped epiphyses, brachydactyly, and hearing loss in some affected individuals were emphasized as unique findings [Adès et al, 1994;Hollaway et al, 1995]. Other reports suggested this syndrome resembled Saethre-Chotzen syndrome [von Gernet et al, 1996;Reardon et al, 1997], or that it resembled Pfeiffer syndrome, without linkage to FGFR1 on chromosome 8, or FGFR2 on chromosome 10 [Bellus et al, 1996;Reardon et al, 1997]. Previous investigators of two families segregating this syndrome had also noted similarities with Ventruto syndrome [Braddock and Graham, 1993;Glass et al, 1994;Ventruto et al, 1976].…”

Section: Introductionmentioning

confidence: 99%

Syndrome of coronal craniosynostosis with brachydactyly and carpal/tarsal coalition due to Pro250Arg mutation in FGFR3 gene

et al. 1998

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Recently, a unique Pro250Arg point mutation in fibroblast growth factor receptor 3 (FGFR3) was reported in 61 individuals with coronal craniosynostosis from 20 unrelated families [Muenke et al. (1997): Am J Hum Genet 60:555-564]. The discovery of this apparently common mutation has resulted in the definition of a recognizable syndrome, through analysis of subtle clinical findings in families who were previously thought to have a variety of other craniosynostosis syndromes. Previous diagnoses in some of these families have included Jackson-Weiss, Saethre-Chotzen, and Pfeiffer syndromes, as well as Adelaide-type craniosynostosis and brachydactyly-craniosynostosis syndrome [Adès et al. (1994): Am J Med Genet 51:121-130; von Gernet et al. (1996): Am J Med Genet 63:177-184; Reardon et al. (1997): J Med Genet 34:632-636; Bellus et al. (1996): Nat Genet 14:174-176; Hollaway et al. (1995): Hum Mol Genet 4:681-683; Glass et al. (1994): Clin Dysmorphol 3:215-223]. There appears to be a need to further delineate the phenotype associated with this common mutation in FGFR3. We compare the clinical characteristics of previously reported cases of this unique Pro250Arg mutation with those of two additional families and suggest that this syndrome with a unique mutational basis be designated coronal craniosynostosis with brachydactyly and carpal/tarsal coalition due to Pro250Arg mutation in FGFR3 gene, to emphasize the distinctive findings which may be present even in the absence of coronal craniosynostosis.

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“…Apart from craniosynostosis, which in Saethre–Chotzen syndrome usually affects one or both coronal sutures, facial anomalies such as a low frontal hairline, facial asymmetry, ptosis, hypertelorism, and dysplastic ears can be present. Furthermore, specific limb abnormalities including brachydactyly, syndactyly of digit II and III on both hands and feet, and fifth digit clinodactyly are seen in patients with Saethre–Chotzen syndrome (1–3). The Saethre–Chotzen syndrome was found to result from mutations in the TWIST gene, located on chromosome 7p21.1.…”

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Deletion of the TWIST gene in a large five‐generation family

et al. 2004

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In this article, we describe a large five-generation family with characteristics of the Saethre-Chotzen syndrome as well as of the blepharophimosis ptosis epicanthus inversus syndrome. Segregating with their phenotype is a deletion of the chromosome 7p21 TWIST gene locus. The TWIST gene indeed is involved in Saethre-Chotzen syndrome, a craniosynostosis syndrome further characterized by specific facial and limb abnormalities. However, only two members of our family exhibited craniosynostosis. This report demonstrates that the genetics of craniofacial anomalies are less straightforward than they sometimes appear to be. Not only craniosynostosis, but also subtle facial deformities could be indicative of an abnormality of the TWIST gene. In conclusion, the clinical spectrum of genetic abnormalities of the TWIST gene is highly variable. We therefore recommend that genetic analysis of the TWIST gene locus, including fluorescence in situ hybridization, should be considered in familial cases of facial and eyelid abnormalities without the presence of craniosynostosis.

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Craniosynostosis suggestive of Saethre-Chotzen syndrome: Clinical description of a large kindred and exclusion of candidate regions on 7p

Cited by 14 publications

References 24 publications

Phenotypic expression of the fibroblast growth factor receptor 3 (FGFR3) mutation P250R in a large craniosynostosis family.

Phenotypic expression of the fibroblast growth factor receptor 3 (FGFR3) mutation P250R in a large craniosynostosis family.

Syndrome of coronal craniosynostosis with brachydactyly and carpal/tarsal coalition due to Pro250Arg mutation in FGFR3 gene

Deletion of the TWIST gene in a large five‐generation family

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