CoChat
Sign Up
Cited by 34Craniofacial Disorders and TreatmentsGenomics and Rare Diseasesdental development and anomalies

Familial scaphocephaly syndrome caused by a novel mutation in the FGFR2 tyrosine kinase domain

Open access
McGillivray, G, Savarirayan, R, Cox, T C, Stojkoski, C, McNeil, R, Bankier, A, Bateman, J F, Roscioli, T +2 more·2005·Journal of Medical Genetics
DOI 10.1136/jmg.2004.027888PMC PMC1736114
Open this paper in CoChat — free accountOpen PDF

Abstract

raniosynostosis, the premature fusion of one or more sutures of the skull, is a common craniofacial anomaly, with an estimated incidence of 1/2000 to 1/3000 births. 1 2 Characteristic deformities of skull shape occur as a result of different patterns of sutural fusion, while compensatory skull expansion occurs at unaffected sutures to accommodate the growing brain.Premature fusion of the sagittal suture, for example, results in anterior to posterior elongation of the skull known as scaphocephaly. 2 Sagittal synostosis is the most common type of craniosynostosis, occurring in 40-58% of cases reported in large neurosurgical surveys, and shows a male predominance.3-6 Most of the cases in these reports are ''non-syndromic'' instances of sagittal synostosis, while familial cases represent 2-9% of the total.Mental retardation is uncommon in isolated sagittal synostosis, but is more common in cases with associated malformations.4-6 Over 90 syndromic forms of craniosyno- stosis have been described.Apert, Crouzon, Pfeiffer, Muenke, and Saethre-Chotzen syndromes are the most common of these, being classified according to the clinical involvement of the cranium, face, hands and feet, and other organs.2 In these syndromes, brachycephaly or acrocephaly resulting from coronal synostosis is the predominant cranial deformity, and this is variably associated with mid-face hypoplasia, broad toes, syndactyly, and intellectual deficits.Sagittal synostosis is seen almost exclusively in combination with coronal synostosis, 2 while macrocephaly in the absence of craniosynostosis occurs infrequently.7 Familial scaphocephaly syndromes, which include Berant syndrome, ''Philadelphia'' type craniosynostosis, and Jones craniosynostosis, 2 are rare and their molecular aetiology remains unknown.Mutations in five genes have been shown to cause various craniosynostosis syndromes.These are the transcription factor genes TWIST (Saethre-Chotzen syndrome, MIM 101400) and MSX2 (Boston-type craniosynostosis, MIM 604757), and three fibroblast growth factor receptor genes, FGFR1, FGFR2, and FGFR3 (Pfeiffer syndrome, MIM 101600; Apert syndrome MIM 101200; Crouzon syndrome, MIM 123500; Jackson-Weiss syndrome, MIM 123500). 1 Mutations in TWIST, FGFR2, and FGFR3 also cause isolated nonsyndromic coronal synostosis 8 ; however, mutations resulting in isolated sagittal suture synostosis and scaphocephaly have yet to be identified.The FGFR mutations have been located predominantly in hotspots in these genes in the more than 800 patients where mutations have been characterised. 1 9 Only one FGFR1 mutation, P252R, has been identified and it results in a mild Pfeiffer syndrome variant.10 In contrast, FGFR2 mutations are a common cause of several craniosynostosis syndromes: Pfeiffer, Apert, Crouzon, Jackson-Weiss, and Beare-Stevenson (MIM 123790). 1 11 The FGFR2 muta- tions are non-randomly distributed throughout the gene, concentrated in exons 8 and 10.Two mutations, S252W and P253R, are relatively common and invariably cause Apert

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1136/jmg.2004.027888

Cites

26 of 26 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The majority of studies reported an odds ratio of male occurring CS ranging from 1.46 to 4.5, with a geometric mean of ~2.7.

    “The majority of the studies studied the odds ratio of male occurring CS with an OR ranging from 1.46 to 4.5 (with geometric mean of ~ 2.7) [2, 3, 15, 26, 50, 53, 74, 80, 82, 86, 96–98, 102, 103, 117].”

    From Genetics versus environment in the pathophysiology of sagittal synostosis (2026) · cites this paper as [86]

    The introductory passage labelled Abstract (page unavailable) says sagittal synostosis shows a male predominance. It gives no male odds ratio, range of 1.46–4.5, or geometric mean of approximately 2.7, and its statement concerns sagittal synostosis rather than craniosynostosis generally. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Variants in genes such as FGFR2, TCF12, ERF, KAT6B, ACTB, SH3PXD2B, SALL1, IFT140, SON, CASK, FOXP2, EXTL3, and SOX6 have often been identified in patients with additional dysmorphic, skeletal, neurodevelopmental, or systemic disorders.

    “More broadly, variants in genes such as FGFR2, TCF12, ERF, KAT6B, ACTB, SH3PXD2B, SALL1, IFT140, SON, CASK, FOXP2, EXTL3, and SOX6 have often been identified in patients with additional dysmorphic, skeletal, neurodevelopmental, or systemic disorders [41, 47–49, 78, 84, 86, 90, 100, 101, 108–110].”

    From Genetics versus environment in the pathophysiology of sagittal synostosis (2026) · cites this paper as [86]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

3 of the 29 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Lajeunie E, Le Merrer M, Bonaiti-Pellie C, Marchac D, Renier D. Genetic study of scaphocephaly. Am J Med Genet 1996;62(3):282-5.
  2. Passos-Bueno MR, Wilcox WR, Jabs EW, Sertie AL, Alonso LG, Kitoh H. Clinical spectrum of fibroblast growth factor receptor mutations. Hum Mutat 1999;14:115-25.

Cited by

Sorted by citations

Related

Authors
McGillivray, G., Savarirayan, R., Cox, T. C., Stojkoski, C., McNeil, R., Bankier, A., Bateman, J. F., Roscioli, T., Gardner, R. J. M., & Lamandé, S. R.
Affiliations
  • Royal Children's Hospital (AU)
  • The University of Adelaide (AU)
  • Murdoch Children's Research Institute (AU)
  • Prince of Wales Hospital (AU)
Corresponding author
Lamandé, S R
ORCID
Venue
Journal of Medical Genetics
Publisher
BMJ
Published
2005-08
Volume
42
Issue
8
Pages
656-662
ISSN
  • 0022-2593 (ISSN-L)
  • 1468-6244
DOI
10.1136/jmg.2004.027888
PMC
PMC1736114
OpenAlex
W2152471249
Cited by
34
References
29
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2018: 2 · 2017: 2 · 2016: 6 · 2015: 2 · 2014: 1 · 2013: 3 · 2012: 2
FWCI
0.90
Type
journal article
Language
en
Open access
Locations
  • Journal of Medical Genetics (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
Funders
  • University of Adelaide
  • Medical Research Council
  • National Health and Medical Research Council
  • National Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Craniofacial Disorders and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
Keywords
craniosynostosis, FGFR2, tyrosine kinase domain mutations
MeSH terms
Abnormalities, Multiple, Craniosynostoses, DNA Mutational Analysis, Female, Genetic Testing, Humans, Male, Intellectual Disability, Models, Molecular, Mutation, Pedigree, Skull, Syndrome, Protein Structure, Tertiary, Receptor, Fibroblast Growth Factor, Type 2

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review