PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “CRANIOSYNOSTOSES”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources
PubMed1999

Maternal smoking and craniosynostosis.

To investigate a possible association between maternal smoking during pregnancy and craniosynostosis (premature closure of one or more of the cranial sutures), a study was conducted using Swedish health registries. Infants with craniosynostosis (n = 304) without a known chromosome anomaly were selected among 1,413,811 infants born between 1983-1996 with known smoking exposure in early pregnancy. A statistically significant association between maternal smoking and craniosynostosis was found (adjusted odds ratio (OR), 1.45; 95% confidence interval (CI), 1.13-1.87), but this association was only valid for isolated defects (OR, 1.67; 95% CI, 1.27-2.19). For associated craniosynostosis (malformation syndromes included), a negative (nonsignificant) association with maternal smoking was indicated instead. For isolated craniosynostosis (all types), a dose-dependent effect of maternal smoking was indicated (OR and 95% CI for smoking <10 cigarettes/day, 1.45 (1.04-2.02); OR and 95% CI for smoking >/=10 cigarettes/day, 2.12 (1.50-2.99)), but was not statistically significant. Among the different types of craniosynostosis, premature closure of the sagittal suture showed the strongest association with maternal smoking (OR, 1.48; 95% CI, 1. 02-2.14), whereas for coronal suture defects, no association with maternal smoking could be detected (OR, 1.02; 95% CI, 0.47-2.21). As no obvious confounders were detected, the present study supports an earlier report of an association between maternal smoking during pregnancy and at least some types of craniosynostosis.

Adult↗
PubMed1999

Three-dimensional morphological analysis of isolated metopic synostosis.

Morphological differences were quantified in three-dimensions among individuals with untreated isolated metopic synostosis and between those individuals and similar aged-matched normal dry skulls to test two hypotheses: first, that the dysmorphology is a self-correcting condition; and second, that a lack of vertical growth of the skull produces this dysmorphology. Three-dimensional (3D) coordinates were recorded for 22 craniofacial landmarks from CT scans of 15 metopic patients, ranging from 5- to 32-months-old, and of four normal dry skulls, ranging in age from 6- to 36-months-old. The patient population was diagnosed with isolated metopic synostosis at The Johns Hopkins Medical Institutions in Baltimore, Maryland or Children's Hospital in St. Louis, Missouri. Comparisons between the metopic age groups indicate that the trigonocephalic phenotype worsens through time. Between 5 and 14 months, the neurocranium displays an increase in vertical growth. This was followed by a lack of vertical growth between 14 and 32 months. The face displays a lack of vertical growth from 5 to 14 months and an increase in vertical growth after 14 months. Comparisons between the metopic age groups and the normal skulls indicate that the trigonocephalic head is taller superoinferiorly and longer anteroposteriorly. Relative to the normal phenotype, the inferior temporal region in the metopic phenotype is narrow. These findings enabled the rejection of both hypotheses and localized form differences between normal and metopic phenotypes. Based on these results, we suggest that the trigonocephalic phenotype worsens with age and the amount of vertical growth that produces the trigonocephalic phenotype varies throughout growth with respect to location within the skull and age.

Age Factors↗
PubMed1997

Mutation associated with Crouzon syndrome causes ligand-independent dimerization and activation of FGF receptor-2.

FGF signaling is clearly important for proper bone development, and several autosomally dominant forms of genetic bone disorders have been mapped to FGF receptors 1, 2, and 3. We have studied the biological effects of the most commonly mutated cysteine residue in FGFR-2 which is detected in individuals with Crouzon syndrome, an autosomally dominant trait which causes premature fusion of the skull bones (craniosynostosis). This Crouzon mutation replaces the cysteine at position 342 with tyrosine, thus disrupting the formation of the third immunoglobulin (Ig)-like loop in the extracellular portion of the receptor. By transfecting mutated and wild-type receptors into a variety of cell lines, we have shown that the C342Y mutation in FGFR-2 produces a receptor which is constitutively activated and capable of transforming NIH3T3 cells and preventing the differentiation of C2 myoblasts in the absence of ligand. Constitutive activation appears to result from the ability of this receptor to form stable interreceptor dimers which involve disulfide bonds between the remaining free cysteine in the mutant receptor. The altered conformation of the third Ig-like domain in the mutated receptor also results in a drastically reduced ability to bind FGF-1 or FGF-2 and in a reduced level of receptor glycosylation. Thus it appears that Crouzon syndrome results from constitutive activation of FGFR-2 and that uncontrolled FGF signaling produces alterations of intramembranous bone development and premature closing of cranial sutures.

3T3 Cells↗
PubMed2001

Regulation of chondrocyte growth and differentiation by fibroblast growth factor receptor 3.

Both gain-of-function and loss-of-function mutations in fibroblast growth factor receptor 3 (Fgfr3) have revealed unique roles for this receptor during skeletal development. Loss-of-function alleles of Fgfr3 lead to an increase in the size of the hypertrophic zone, delayed closure of the growth plate and the subsequent overgrowth of long bones. Gain-of-function mutations in Fgfr3 have been genetically linked to autosomal dominant dwarfing chondrodysplasia syndromes where both the size and architecture of the epiphyseal growth plate are altered. Analysis of these phenotypes and the biochemical consequences of the mutations in FGFR3 demonstrate that FGFR3-mediated signalling is an essential negative regulator of endochondral ossification.

Amino Acid Sequence↗
PubMed2001

Genetic control of the cell proliferation-differentiation balance in the developing skull vault: roles of fibroblast growth factor receptor signalling pathways.

Activating mutations of genes encoding the transmembrane tyrosine kinase receptors fibroblast growth factor receptors (FGFRs)1-3, and haploinsufficiency of the transcription factor TWIST, cause human craniosynostosis syndromes that typically involve the coronal suture. We have investigated the functional roles of these genes in development of the coronal suture in mouse fetuses, and tested the effects of increasing FGFR signalling by applying exogenous FGF2 to the suture. The results indicate that the proliferation-differentiation balance in normal sutural development involves a gradient of extracellular FGF from the region of differentiation, in which Fgfr1 is expressed, to the sutural mesenchyme, in which low levels of FGF are associated with Fgfr2 expression in osteogenic stem cells. Experimental increase of sutural FGF levels leads to down-regulation of Fgfr2, up-regulation of Fgfr1, up-regulation of the osteogenic differentiation gene Osteopontin, and cessation of proliferation. Twist is expressed in the midsutural mesenchyme and is partially co-expressed with Fgfr2, consistent with the possibility that it is involved in maintaining proliferation through regulating transcription of Fgfr2.

Animals↗
PubMed2001

Craniosynostosis and related limb anomalies.

Many genetically determined craniosynostosis syndromes feature limb anomalies, implying that pathways of cranial suture and limb morphogenesis share some identical components. Identification of heterozygous mutations in FGFR1, FGFR2, FGFR3, TWIST and MSX2 in craniosynostosis has focused particular attention on these genes. Here we explore two themes: use of clinical/molecular analysis to provide new clues to pathophysiology and the contrasting effects of loss- and gain-of-function mutations. Apert syndrome is a severe craniosynostosis/syndactyly disorder usually caused by specific substitutions (Ser252Trp or Pro253Arg) in FGFR2. The relative severity of cranial and limb malformations varies in opposite directions for the two mutations, suggesting that these phenotypes arise by different mechanisms. Clinical and biochemical evidence supports a model in which alternative splice forms of FGFR2 mediate these distinct effects. Pro-->Arg substitutions equivalent the Pro253Arg/FGFR2 mutation occur in both FGFR1 and FGFR3, and are also associated with craniosynostosis. This suggests a common pathological mechanism, whereby enhanced affinity for a limited repertoire of tissue-specific ligand(s) excessively prolongs signalling in the cranial suture. The first MSX2 mutation in craniosynostosis was described in 1993 but this remains the only example. We have recently identified three MSX2 mutations associated with a different cranial phenotype, parietal foramina. DNA binding studies show that the craniosynostosis and parietal foramina arise from gain and loss of function, respectively.

Acrocephalosyndactylia↗
PubMed2000

Fronto-ocular syndrome: newly recognized trigonocephaly syndrome.

We describe an apparently unique disorder, Fronto-Ocular syndrome, present in a mother and her two daughters, and comprising trigonocephaly due to coronal and metopic craniosynostosis, ocular hypotelorism, ocular proptosis and ptosis, epicanthal folds, hypoplastic supraorbital ridges, elevated nasal bridge, thin philtrum, high-arched palate and a narrow bifrontal region. Both daughters have glabellar capillary hemangiomas, a congenital heart defect and mild developmental disabilities. Review of the literature failed to disclose any syndrome with similar findings. It is likely that this disorder represents an autosomal dominant condition, that arose as a new mutation in the mother. Mutational analysis of fibroblast growth factor receptor (FGFR) 1 and FGFR2 failed to identify the molecular basis of the disorder.

Adult↗
PubMed2000

Newly recognised craniosynostosis syndrome that does not map to known disease loci.

We describe a consanguineous family of Pakistani origin with five sibs, three of whom were affected by craniosynostosis of variable presentation. In addition, they had other congenital abnormalities principally affecting neurological, ocular, and limb development. We provide linkage evidence using intragenic and flanking microsatellite markers suggesting that the disease in this family was not caused by a mutation in one of the known craniosynostosis loci (FGFR1, FGFR2, FGFR3, MSX2, TWIST). Given the clinical novelty and parental consanguinity, we hypothesise that the affected individuals were autozygous for a recessively inherited mutation, at a novel locus, predisposing to craniosynostosis.

Child↗
PubMed2001

Syndrome of coronal craniosynostosis, Klippel-Feil anomaly, and sprengel shoulder with and without Pro250Arg mutation in the FGFR3 gene.

A unique Pro250Arg point mutation in fibroblast growth factor receptor 3 (FGFR3) was initially reported by Bellus et al. [1996: Nat Genet 14:174-176] and the phenotype subsequently by Muenke et al. [1997: Am J Hum Genet 60:555-564], Reardon et al. [1997: J Med Genet 34:632-636], and Graham et al. [1998: Am J Med Genet 77:322-329]. These authors emphasized the pleiotropic nature of this form of coronal craniosynostosis, including brachydactyly with carpal and/or tarsal coalitions, with other anomalies at lower frequency. We report on a family with autosomal dominant coronal synostosis, segmentation and fusion anomalies of the vertebra and ribs, and Sprengel shoulder due to the Pro250Arg mutation. We also report a single case with an identical phenotype without the mutation.

Adult↗
PubMed2001

Another TWIST on Baller-Gerold syndrome.

Baller-Gerold syndrome is characterized by craniosynostosis and preaxial upper limb malformations. Wide heterogeneity exists with regard to the presence of additional anomalies. Most of the 31 reported cases involve other malformations, including cardiac, Central Nervous System (CNS), and urogenital anomalies. Baller-Gerold syndrome is thought to have autosomal recessive inheritance. However, Gripp et al. [1999: Am. J. Med. Genet. 82:170-176] recently provided the first evidence for autosomal dominant inheritance with variable expressivity and severity. A nonsense mutation was found in TWIST, a gene associated with Saethre-Chotzen syndrome (SCS). Here we report on a male Caucasian patient of nonconsanguineous parents, with synostosis of the coronal, metopic, and sagittal sutures, and bilateral radial ray hypoplasia. The patient's small, round ears with prominent crus helices, and cervical anomalies are common features of SCS. The father had very mild features of SCS. We identify direct paternal transmission of a novel missense TWIST mutation in the highly conserved Helix II domain of this bHLH-family gene. This report lends further support to the recent findings by Gripp et al. [1999]. Future TWIST mutational analysis on patients with craniosynostosis and radial ray involvement will shed light on whether Baller-Gerold syndrome should be a distinct entity or some cases should be reclassified as a heterogeneous form of SCS.

Abnormalities, Multiple↗
PubMed2002

Craniosynostosis, ectopia lentis, and congenital heart defects: further delineation of an autosomal dominant syndrome with incomplete penetrance.

The association of craniosynostosis with ectopia lentis is extremely rare. This was recently reported in monozygotic twin sisters, supporting a genetic etiology for this syndromic association. We report on female first cousins once removed who were born with unilateral coronal synostosis. One cousin also had peripheral pulmonic branch stenosis at birth and was later found to have ectopia lentis and severe myopia. The other cousin had an atrial septal defect, mitral valve prolapse, and only mild myopia. Their intelligence is normal. The inheritance is likely autosomal dominant with variable expression and incomplete penetrance and further defines this syndrome to include congenital heart defects. These findings will have important implications for genetic counseling.

Adolescent↗
PubMed2002

Craniosynostosis, telecanthus, scalp hair abnormalities, and sensorineural deafness in two sibs.

A sister and a brother with anomalous skull configuration, facial abnormalities, abnormal scalp hair growth, sensorineural hearing loss and, in the boy, proven craniosynostosis, severe mental retardation, and autism were reported in 1986 in an abstract by Hersh et al. We reexamined this family and here review the literature focusing on the major clinical findings, and suggest that their clinical manifestations may represent a previously unreported syndrome.

Abnormalities, Multiple↗
PubMed2002

Possible third case of Lin-Gettig syndrome.

We report a patient with craniosynostosis, severe mental retardation, absence of the corpus callosum, camptodactyly, hypogonadism, and ventricular septal defect. We propose that he has Lin-Gettig syndrome and that he is the third reported patient with this entity. Our patient also had additional phenotypic features, including palatal cleft and absent rapid eye movement (REM) sleep that were not present in the two previously described patients with this syndrome. High-resolution karyotype and subtelomeric fluorescence in situ hybridization (FISH) for cryptic telomeric rearrangement were normal. The existence of an unrelated patient with Lin-Gettig syndrome supports that this is a separate and distinct clinical entity.

Abnormalities, Multiple↗