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Journal of Cranio-maxillo-facial... Jan 2024Craniosynostosis, characterized by premature fusion of one or more cranial sutures, results in a distorted skull shape. Only three studies have assessed facial asymmetry...
Craniosynostosis, characterized by premature fusion of one or more cranial sutures, results in a distorted skull shape. Only three studies have assessed facial asymmetry manually in unicoronal synostosis patients. It is therefore important to understand how uni- and bicoronal synostosis affect facial asymmetry with a minimum risk of human bias. An automated algorithm was developed to quantify facial asymmetry from three-dimensional images, generating a mean facial asymmetry (MFA) value in millimeters to reflect the degree of asymmetry. The framework was applied to analyze postoperative 3D images of syndromic patients (N = 35) diagnosed with Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis with respect to MFA values from a healthy control group (N = 89). Patients demonstrated substantially higher MFA values than controls: Muenke syndrome (unicoronal 1.74 ± 0.40 mm, bicoronal 0.77 ± 0.21 mm), Saethre-Chotzen syndrome (unicoronal 1.15 ± 0.20 mm, bicoronal 0.69 ± 0.16 mm), and TCF12-related craniosynostosis (unicoronal 1.40 ± 0.51 mm, bicoronal 0.66 ± 0.05 mm), compared with controls (0.49 ± 0.12 mm). Longitudinal analysis identified an increasing MFA trend in unicoronal synostosis patients. Our study revealed higher MFA in syndromic patients with uni- and bicoronal synostosis compared with controls, with the most pronounced MFA in Muenke syndrome patients with unilateral synostosis. Bicoronal synostosis patients demonstrated higher facial asymmetry than expected given the condition's symmetrical presentation.
Topics: Humans; Infant; Retrospective Studies; Facial Asymmetry; Craniosynostoses; Acrocephalosyndactylia
PubMed: 38135649
DOI: 10.1016/j.jcms.2023.11.006 -
European Journal of Human Genetics :... Dec 2014TCF12 mutations have been reported very recently in coronal synostosis. We report several cases of familial coronal synostosis among four families harbouring novel TCF12...
TCF12 mutations have been reported very recently in coronal synostosis. We report several cases of familial coronal synostosis among four families harbouring novel TCF12 mutations. We observed a broad interfamilial phenotypic spectrum with features overlapping with the Saethre-Chotzen syndrome. TCF12 molecular testing should be considered in patients with unilateral- or bilateral-coronal synostosis associated or not with syndactyly, after having excluded mutations in the TWIST1 gene and the p.Pro250Arg mutation in FGFR3.
Topics: Acrocephalosyndactylia; Basic Helix-Loop-Helix Transcription Factors; DNA Mutational Analysis; Female; Humans; Infant; Male; Molecular Sequence Data; Mutation; Nuclear Proteins; Pedigree; Receptor, Fibroblast Growth Factor, Type 3; Synostosis; Twist-Related Protein 1
PubMed: 24736737
DOI: 10.1038/ejhg.2014.57 -
Ginekologia Polska 2016n/a.
n/a.
Topics: Acrocephalosyndactylia; Fatal Outcome; Female; Fetal Diseases; Hernias, Diaphragmatic, Congenital; Humans; Live Birth; Pregnancy; Prenatal Diagnosis; Ultrasonography, Prenatal
PubMed: 28098935
DOI: 10.5603/GP.2016.0097 -
PloS One 2015Apert syndrome (AS) is a type of autosomal dominant disease characterized by premature fusion of the cranial sutures, severe syndactyly, and other abnormalities in...
Apert syndrome (AS) is a type of autosomal dominant disease characterized by premature fusion of the cranial sutures, severe syndactyly, and other abnormalities in internal organs. Approximately 70% of AS cases are caused by a single mutation, S252W, in fibroblast growth factor receptor 2 (FGFR2). Two groups have generated FGFR2 knock-in mice Fgfr2S252W/+ that exhibit features of AS. During the present study of AS using the Fgfr2S252W/+ mouse model, an age-related phenotype of bone homeostasis was discovered. The long bone mass was lower in 2 month old mutant mice than in age-matched controls but higher in 5 month old mutant mice. This unusual phenotype suggested that bone marrow-derived mesenchymal stem cells (BMSCs), which are vital to maintain bone homeostasis, might be involved. BMSCs were isolated from Fgfr2S252W/+ mice and found that S252W mutation could impair osteogenic differentiation BMSCs but enhance mineralization of more mature osteoblasts. A microarray analysis revealed that Wnt pathway inhibitors SRFP1/2/4 were up-regulated in mutant BMSCs. This work provides evidence to show that the Wnt/β-catenin pathway is inhibited in both mutant BMSCs and osteoblasts, and differentiation defects of these cells can be ameliorated by Wnt3a treatment. The present study suggested that the bone abnormalities caused by deregulation of Wnt pathway may underlie the symptoms of AS.
Topics: Acrocephalosyndactylia; Animals; Bone Matrix; Calcification, Physiologic; Mice; Mice, Mutant Strains; Receptor, Fibroblast Growth Factor, Type 2; Wnt Signaling Pathway
PubMed: 25693202
DOI: 10.1371/journal.pone.0112716 -
Anesthesia Progress 2015Apert syndrome is a rare autosomal dominant disorder characterized by craniofacial abnormalities, craniosynostosis and syndactyly. Nasotracheal intubation for a patient...
Apert syndrome is a rare autosomal dominant disorder characterized by craniofacial abnormalities, craniosynostosis and syndactyly. Nasotracheal intubation for a patient with Apert syndrome can be a challenge because of abnormal facial anatomy. We experienced the anesthetic management of a patient with Apert syndrome who underwent partial resection of mandible and cleft palate repair with nasotracheal intubation. Nasotracheal intubation using a gastric tube and extubation using an airway exchange catheter proved useful in this case of airway compromise.
Topics: Acrocephalosyndactylia; Adolescent; Airway Extubation; Airway Obstruction; Anesthetics, Inhalation; Female; Humans; Intubation, Gastrointestinal; Intubation, Intratracheal; Laryngoscopes; Mandibular Neoplasms; Methyl Ethers; Odontogenic Tumors; Postoperative Complications; Sevoflurane
PubMed: 26398130
DOI: 10.2344/0003-3006-62.3.122 -
Taiwanese Journal of Obstetrics &... Aug 2017
Topics: Acrocephalosyndactylia; Adult; Female; Gestational Age; Humans; Pregnancy; Prenatal Diagnosis; Tomography, Spiral Computed; Ultrasonography, Prenatal
PubMed: 28805624
DOI: 10.1016/j.tjog.2016.11.008 -
Genetics in Medicine : Official Journal... Feb 2019Among children with FGFR2-associated Pfeiffer syndrome, those with the W290C pathogenic variant (PV) are reported to have the worst clinical outcomes. Mortality is high,...
A genotype-specific surgical approach for patients with Pfeiffer syndrome due to W290C pathogenic variant in FGFR2 is associated with improved developmental outcomes and reduced mortality.
PURPOSE
Among children with FGFR2-associated Pfeiffer syndrome, those with the W290C pathogenic variant (PV) are reported to have the worst clinical outcomes. Mortality is high, and severe neurocognitive impairment has been reported in all surviving patients. However, it is unclear whether these poor outcomes are an unavoidable consequence of the PV itself, or could be improved with a genotype-specific treatment approach. The purpose of this report is to describe the more intensive surgical approach used for each of the three patients with W290C PV in FGFR2 at our center, all of whom survived and have normal neurocognitive functioning.
METHODS
Retrospective chart review.
RESULTS
In contrast to other patients with Pfeiffer syndrome at our center, all three patients who were subsequently found to have a W290C PV required a similar and more aggressive approach based on early cephalocranial disproportion. In contrast to previously reported W290C cases, each of our three patients survived and demonstrate normal neurocognitive functioning.
CONCLUSION
While previously reported outcomes in W290C-associated Pfeiffer syndrome have been extremely poor, we present three patients who underwent an intensive surgical approach and have normal development. This suggests that a personalized and aggressive surgical approach for children with W290C PV may dramatically improve clinical outcome.
Topics: Acrocephalosyndactylia; Child; Child, Preschool; Cohort Studies; Female; Genotype; Humans; Infant; Infant, Newborn; Mutation; Receptor, Fibroblast Growth Factor, Type 2; Retrospective Studies; Surgical Procedures, Operative; Treatment Outcome
PubMed: 29915381
DOI: 10.1038/s41436-018-0073-x -
Revista Argentina de Microbiologia 2014We report a case of a brain abscess caused by Haemophilus influenzae type e in a 12 year-old patient suffering from Apert syndrome. Apert syndrome is characterized by...
We report a case of a brain abscess caused by Haemophilus influenzae type e in a 12 year-old patient suffering from Apert syndrome. Apert syndrome is characterized by the premature closure of cranial sutures. In 2010 the patient suffered head trauma in the frontal area with cranial fracture and a cerebrospinal fluid fistula. In February 2013 he was admitted to hospital with fever, vomiting and generalized tonic-clonic seizure with deteriorating mental status/progressive sensory impairment. The computerized axial tomographic scan showed a right frontal lesion, perilesional edema, mild ventricular dilatation and pansinusitis. A brain abscess was diagnosed and drained. The clinical sample was then cultured. A gram negative coccobacillus was isolated and identified as Haemophilus influenzae serotype e. Empirical treatment was started with meropenem (120 mg/kg/day) and vancomycin (60 mg/kg/day), which was later switched to ceftriaxone (100 mg/kg/day) and metronidazole (500 mg/8 h) after culture results arrived. The patient was discharged in good clinical condition.
Topics: Acrocephalosyndactylia; Brain Abscess; Child; Haemophilus Infections; Haemophilus influenzae; Humans; Male
PubMed: 25576411
DOI: 10.1016/S0325-7541(14)70085-9 -
Journal of Medical Case Reports Aug 2019Apert syndrome, Online Mendelian Inheritance in Man number 101200, is a rare genetic condition, with autosomal dominant inheritance, characterized by craniosynostosis,...
BACKGROUND
Apert syndrome, Online Mendelian Inheritance in Man number 101200, is a rare genetic condition, with autosomal dominant inheritance, characterized by craniosynostosis, midfacial malformation, and severe symmetrical syndactyly. Apert syndrome is associated with other systemic malformations, including intellectual disability. At least seven mutations in fibroblast growth factor receptor 2 (FGFR2) gene have been found to cause Apert syndrome. Most cases of Apert syndrome are caused by one of the two most frequent mutations located in exon 7 (Ser252Trp or Pro253Arg).
CASE PRESENTATION
A 27-year-old Javanese man presented borderline intellectual functioning and striking dysmorphisms. A clinical diagnosis of Apert syndrome was previously made based on these clinical features. Furthermore, POSSUM software was used before molecular analysis and the result showed suspected Apert syndrome with a cut-off point of 14. Molecular genetic analysis of FGFR2, targeting exon 7, was performed by direct sequencing. In this patient, a missense mutation c.755C>G was detected, changing a serine into a tryptophan (p.Ser252Trp).
CONCLUSION
We report the case of an Indonesian man with Apert syndrome with a c.755C>G (p.Ser252Trp) mutation in the FGFR2 gene. Our patient showed similar dysmorphism to previously reported cases, although cleft palate as a typical feature for p.Ser252Trp mutation was not present. In spite of the accessibility of molecular genetic testing in a few parts of the world, the acknowledgement of clinically well-defined syndromes will remain exceptionally imperative in developing countries with a lack of diagnostic facilities.
Topics: Abnormalities, Multiple; Acrocephalosyndactylia; Adult; High-Throughput Nucleotide Sequencing; Humans; Indonesia; Male; Mutation, Missense; Receptor, Fibroblast Growth Factor, Type 2; Sequence Analysis, DNA
PubMed: 31387623
DOI: 10.1186/s13256-019-2173-x -
Taiwanese Journal of Obstetrics &... Jun 2017
Pfeiffer syndrome with FGFR2 C342R mutation presenting extreme proptosis, craniosynostosis, hearing loss, ventriculomegaly, broad great toes and thumbs, maxillary hypoplasia, and laryngomalacia.
Topics: Abnormalities, Multiple; Acrocephalosyndactylia; Humans; Infant, Newborn; Male; Mutation; Receptor, Fibroblast Growth Factor, Type 2
PubMed: 28600064
DOI: 10.1016/j.tjog.2017.04.030