Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ACROCEPHALOSYNDACTYLIA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 181 records · Page 10Linked to original sources
PubMed1987

Describing a craniofacial anomaly: finite elements and the biometrics of landmark locations.

An intergroup comparison of cephalometric landmark configurations by the finite-element method elegantly depicts the algebra of some of the size and shape change measures that one may define by reference to those landmarks. In studies of mean differences between groups, the statistical analysis of these finite elements is equivalent to competent statistical analysis of the same data using any other geometric metaphor, such as properly standardized vector descriptions of landmark "movement" or scalar measures, size and shape variables, taken in sufficient variety. In applications to landmark data, the reality of finite-element depictions is purely statistical rather than phenomenological. In the absence of additional evidence, they should not be held either more or less biologically meaningful than other descriptions of the same landmark changes to which they lead. These propositions are exemplified using landmark data from 13 cases of Apert syndrome.

Acrocephalosyndactylia↗
PubMed1991

Euclidean distance matrix analysis: a coordinate-free approach for comparing biological shapes using landmark data.

For problems of classification and comparison in biological research, the primary focus is on the similarity of forms. A biological form can be conveniently defined as consisting of size and shape. Several approaches for comparing biological shapes using landmark data are available. Lele (1991a) critically discusses these approaches and proposes a new method based on the Euclidean distance matrix representation of the form of an object. The purpose of this paper is to extend this new methodology to the comparison of groups of objects. We develop the statistical versions of various concepts introduced by Lele (1991a) and use them for developing statistical procedures for testing the hypothesis of shape difference between biological forms. We illustrate the use of this method by studying morphological differences between normal children and those affected with Crouzon and Apert syndromes and craniofacial sexual dimorphism in Cebus apella.

Acrocephalosyndactylia↗
PubMed1992

On comparing biological shapes: detection of influential landmarks.

For problems of classification and comparison in biological research, the primary focus is on the similarity of forms. A biological form consists of size and shape. Several approaches for comparing biological forms using landmark data are available. If the two biological forms are demonstrated to be different, the next important issue is to localize the differences by identifying those areas which differ most between the two objects. In this paper we suggest a technique to detect influential landmarks, those which contribute most to the difference between forms. We study the effectiveness of the technique using three-dimensional simulated data sets and two examples. Results suggest that the technique is useful in the study of biological form and its variation.

Acrocephalosyndactylia↗
PubMed2002

Craniosynostosis in Twist heterozygous mice: a model for Saethre-Chotzen syndrome.

Saethre-Chotzen syndrome is a common autosomal dominant form of craniosynostosis, the premature fusion of the sutures of the calvarial bones of the skull. Most Saethre-Chotzen syndrome cases are caused by haploinsufficiency for the TWIST gene. Mice heterozygous for a null mutation of the Twist gene replicate certain features of Saethre-Chotzen syndrome, but have not been reported to exhibit craniosynostosis. We demonstrate that Twist heterozygous mice exhibit fusions of the coronal suture and other cranial suture abnormalities, indicating that Twist heterozygous mice constitute a better animal model for Saethre-Chotzen syndrome than was previously appreciated.

Acrocephalosyndactylia↗
PubMed2006

Further evidence of association between mutations in FGFR2 and syndromic craniosynostosis with sacrococcygeal eversion.

BACKGROUND: Pfeiffer syndrome (PS; OMIM #101600) is an autosomal dominant disorder characterized by craniosynostosis, midface hypoplasia, broad thumbs, brachydactyly, broad great toes, and variable syndactyly. CASE: We report a case of PS (type 3) with tracheal and visceral involvement and sacrococcygeal eversion. The patient shows facial dysmorphism with macrocephaly, dolichocephaly, and trigonocephaly, and an asymmetric skull, bilateral and severe exophthalmia with shallow orbits and ocular hypertelorism, downslanting palpebral fissures, constant strabismus, short anterior cranial base, and midface hypoplasia. CONCLUSIONS: Molecular analysis of the FGFR2 gene in this patient revealed a point mutation (c.890G>C NM_000141). This mutation leads to the substitution of the residue tryptophan at position 290 to cysteine in the protein (p.Try290Cys). These data reinforce the hypothesis that the p.Trp290Cys mutation is more often associated with a severe and poor prognosis of PS. Furthermore they suggest that the presence of sacrococcygeal defects is not associated with any specific FGFR2 mutation.

Acrocephalosyndactylia↗
PubMed2005

P253R fibroblast growth factor receptor-2 mutation induces RUNX2 transcript variants and calvarial osteoblast differentiation.

Unregulated fibroblast growth factor 2 (FGF2) signaling caused by mutations in the fibroblast growth factor receptor (FGFR2) leads to human craniosynostosis such as the Apert syndrome. In an in vitro control model of calvarial osteoblasts from Apert patients carrying the FGFR2 P253R mutation, we studied the changes in cellular phenotype and evaluated the effects of FGF2. Compared with wild-type controls, osteocalcin mRNA was down-regulated in Apert osteoblasts, Runt-related transcription factor-2 (RUNX2) mRNA was differentially spliced, and FGF2 secretion was greater. Total protein synthesis, fibronectin and type I collagen secretion were up-regulated, while protease and glycosidase activities and matrix metalloproteinase-13 (MMP-13) transcription were decreased, suggesting an altered ECM turnover. Adding FGF2 increased protease and glycosidase activities and down-regulated fibronectin and type I collagen secretion in Apert osteoblasts. High affinity FGF2 receptors were up-regulated in Apert osteoblasts and analysis of signal transduction showed elevated levels of Grb2 tyrosine phosphorylation and the Grb2-p85 beta association, which FGF2 stimulation strongly reduced. All together these findings suggest increased constitutive receptor activity in Apert mutant osteoblasts and an autocrine loop involving the FGF2 pathway in modulation of Apert osteoblast behavior.

Acrocephalosyndactylia↗
PubMed2005

Fibroblast growth factor receptor 2, gain-of-function mutations, and tumourigenesis: investigating a potential link.

Activating germline mutations in the fibroblast growth factor receptor (FGFR) gene family have been identified in several dominantly inherited skeletal disorders; in the case of FGFR3, the same somatically arising mutations have also been isolated from a variety of tumour tissues. Whilst the role of FGFR2 mutations in congenital syndromes has been well documented, their relationship with cancer has not been clearly defined. Based on evidence that gain-of-function mutations in FGFR2 drive positive selection in adult spermatogonia, the present study investigated, by denaturing high-performance liquid chromatography (DHPLC), DNA sequencing, and restriction digestion, the prevalence of FGFR2 mutations in 58 tumour cell lines of various types, and 29 testicular germ cell tumour samples. Although sequence variations and allelic imbalance were identified in FGFR2, none of the previously documented dominant mutations was detected in any of the tumour types examined. This suggests that gain-of-function FGFR2 mutations are not commonly encountered in tumourigenesis and specifically excludes a major contribution in testicular tumours.

Acrocephalosyndactylia↗
PubMed2006

Apert syndrome: what prenatal radiographic findings should prompt its consideration?

Apert syndrome was diagnosed in a newborn with typical facial and digital features whose only detected prenatal abnormality had been agenesis of the corpus callosum. This prompted a review of the central nervous system findings in all cases of Apert syndrome treated at the Craniofacial Center Boston Children's Hospital between 1978 and 2004. Two of 30 patients with Apert syndrome had prenatal identification of mild dilatation of the lateral cerebral ventricles and complete agenesis of the corpus callosum (ACC) documented with both ultrasound and MRI. Both had the common S252W mutation of FGFR2. Though cranial and orbital malformations typical of Apert were eventually seen in these fetuses in the third-trimester, even in retrospect, these were not detectable at mid second-trimester, ultrasound screening for congenital malformations. Hand malformations also went undetected in the second-trimester despite extensive imaging by experienced radiologists. We conclude that prenatal ultrasonographic identification of mild ventriculomegaly or ACC should stimulate a careful search for features of Apert syndrome and prompt follow-up imaging to look for bony abnormalities that have later onset. Prenatal molecular testing for Apert mutations should be considered in cases of mild ventriculomegaly and ACC.

Acrocephalosyndactylia↗
PubMed1991

Prenatal ultrasound diagnosis of Apert's syndrome.

A mother affected with Apert's syndrome was diagnosed by ultrasound scan at 16-17 weeks to have a fetus similarly affected. The typical features of acrocephaly and symmetrical syndactyly were seen. This is probably the first time that this condition has been diagnosed at such a gestation by ultrasound scan. The patient decided to continue the pregnancy, and intrauterine death occurred at 34 weeks. The diagnosis was confirmed by pathological examination.

Acrocephalosyndactylia↗
PubMed2003

Prenatal diagnosis of Apert syndrome: report of two cases.

Two de novo cases with Apert Syndrome detected prenatally are presented herein. In the first, fetal ultrasound findings of syndactyly of the hands, craniosynostosis and proptosis resulted in a prenatal diagnosis in the nineteenth week of gestation. This is the earliest prenatal diagnosis of this syndrome in a not-at-risk case. Following counseling, this pregnancy was terminated and subsequent pathological examination and DNA analysis confirmed the diagnosis of Apert Syndrome and coarctation of the aorta. In the second case, fetal ultrasound at 21 weeks' gestation revealed a hypoplastic left heart and clover-leaf skull. Following counseling, this pregnancy was also terminated. Further examination of the fetus and DNA analysis led to a diagnosis of Apert Syndrome. These cases emphasize the need to complete a thorough fetal ultrasound in cases with potentially lethal cardiac abnormality and the importance of incorporating a fetal pathologist, as well as a medical geneticist, in the investigations performed after delivery or pregnancy termination when a fetal abnormality is detected on ultrasound.

Abortion, Induced↗
PubMed2004

Prenatal ultrasound diagnosis of a case of Pfeiffer syndrome without cloverleaf skull and review of the literature.

Pfeiffer syndrome is characterized by bilateral coronal craniosynostosis, midface hypoplasia, beaked nasal tip, broad and medially deviated thumbs and great toes. Originally, it was described in eight persons from three generations in a pedigree consistent with an autosomal dominant transmission. Since then, several reports have documented its high clinical and genetic heterogeneity. The condition is usually detected in the newborn period or later, and very few prenatal ultrasound diagnoses have been reported. We present a case of Pfeiffer syndrome prenatally diagnosed at 20 weeks' gestation, in which the sonographic features of craniosynostosis, hypertelorism associated with an extreme proptosis, and broad thumb led to the diagnosis, confirmed after termination of pregnancy by dysmorphological, pathological and radiological evaluation. DNA analysis of the fibroblast growth factor receptor 2 (FGFR2) showed a missense mutation consisting in a transversion G --> C at nucleotide 870. This led to a Trp290Cys amino acidic substitution. We discuss the relevant findings of our and previously published cases. Our report demonstrates that a careful sonographic examination can lead to an early prenatal diagnosis of Pfeiffer syndrome also in cases without cloverleaf skull.

Abortion, Induced↗
PubMed2004

Prenatal diagnosis of Pfeiffer syndrome type II.

Pfeiffer syndrome is an autosomal dominant disorder characterized by coronal craniosynostosis, midface hypoplasia, broad thumbs and great toes. On the basis of clinical findings, three subtypes have been delineated. The clinical variability of Pfeiffer syndrome as well as other causes of craniosynostosis can make a prenatal diagnosis based on sonography alone difficult. We describe a fetus in whom sonographic findings (including 3D ultrasound) suggested a Pfeiffer syndrome type II and in which subsequent molecular analysis verified the diagnosis by identifying a de novo mutation in the FGFR2 gene. To the best of our knowledge, this is the first report of a prenatal molecular diagnosis of Pfeiffer syndrome in a patient without family history.

Acrocephalosyndactylia↗