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Clinical Oral Investigations Jul 2019To determine whether the intramaxillary relationship of patients with Muenke syndrome and Saethre-Chotzen syndrome or TCF12-related craniosynostosis are systematically...
OBJECTIVES
To determine whether the intramaxillary relationship of patients with Muenke syndrome and Saethre-Chotzen syndrome or TCF12-related craniosynostosis are systematically different than those of a control group.
MATERIAL AND METHODS
Forty-eight patients (34 patients with Muenke syndrome, 8 patients with Saethre-Chotzen syndrome, and 6 patients with TCF12-related craniosynostosis) born between 1982 and 2010 (age range 4.84 to 16.83 years) that were treated at the Department of Oral Maxillofacial Surgery, Special Dental Care and Orthodontics, Children's Hospital Erasmus University Medical Center, Sophia, Rotterdam, the Netherlands, were included. Forty-seven syndromic patients had undergone one craniofacial surgery according to the craniofacial team protocol. The dental arch measurements intercanine width (ICW), intermolar width (IMW), arch depth (AD), and arch length (AL) were calculated. The control group existed of 329 nonsyndromic children.
RESULTS
All dental arch dimensions in Muenke (ICW, IMW, AL, p < 0.001, ADmax, p = 0.008; ADman, p = 0.002), Saethre-Chotzen syndrome, or TCF12-related craniosynostosis patients (ICWmax, p = 0.005; ICWman, IMWmax, AL, p < 0.001) were statistically significantly smaller than those of the control group.
CONCLUSIONS
In this study, we showed that the dental arches of the maxilla and the mandible of patients with Muenke syndrome and Saethre-Chotzen syndrome or TCF12-related craniosynostosis are smaller compared to those of a control group.
CLINICAL RELEVANCE
To gain better understanding of the sutural involvement in the midface and support treatment capabilities of medical and dental specialists in these patients, we suggest the concentration of patients with Muenke and Saethre-Chotzen syndromes or TCF12-related craniosynostosis in specialized teams for a multi-disciplinary approach and treatment.
Topics: Acrocephalosyndactylia; Adolescent; Child; Child, Preschool; Craniosynostoses; Dental Arch; Female; Humans; Male; Netherlands; Syndrome
PubMed: 30392078
DOI: 10.1007/s00784-018-2710-9 -
European Journal of Human Genetics :... Jan 2015The phenotypic spectrum of GLI3 mutations includes autosomal dominant Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS). PHS was first...
The phenotypic spectrum of GLI3 mutations includes autosomal dominant Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS). PHS was first described as a lethal condition associating hypothalamic hamartoma, postaxial or central polydactyly, anal atresia and bifid epiglottis. Typical GCPS combines polysyndactyly of hands and feet and craniofacial features. Genotype-phenotype correlations have been found both for the location and the nature of GLI3 mutations, highlighting the bifunctional nature of GLI3 during development. Here we report on the molecular and clinical study of 76 cases from 55 families with either a GLI3 mutation (49 GCPS and 21 PHS), or a large deletion encompassing the GLI3 gene (6 GCPS cases). Most of mutations are novel and consistent with the previously reported genotype-phenotype correlation. Our results also show a correlation between the location of the mutation and abnormal corpus callosum observed in some patients with GCPS. Fetal PHS observations emphasize on the possible lethality of GLI3 mutations and extend the phenotypic spectrum of malformations such as agnathia and reductional limbs defects. GLI3 expression studied by in situ hybridization during human development confirms its early expression in target tissues.
Topics: Abnormalities, Multiple; Acrocephalosyndactylia; Cohort Studies; DNA Mutational Analysis; Family; Gene Expression; Gene Rearrangement; Genetic Association Studies; Haploinsufficiency; Humans; In Situ Hybridization, Fluorescence; Kruppel-Like Transcription Factors; Mutation; Nerve Tissue Proteins; Phenotype; Zinc Finger Protein Gli3
PubMed: 24736735
DOI: 10.1038/ejhg.2014.62 -
Augmentative and Alternative... Jun 2019This study aimed to detect patterns in clause construction structural changes produced by four participants aged 9;5-13;7 (years;months) with motor speech disorders who...
This study aimed to detect patterns in clause construction structural changes produced by four participants aged 9;5-13;7 (years;months) with motor speech disorders who used speech-generating devices. Sequences of adult-child interactions, drawn from the data of a larger study focused on enhancing vocabulary and grammar skills, were examined. This current study comprises a secondary analysis of a corpus of 29 conversations totalling 808.36 min, analysing clause structures by type, linguistic complexity, and intensity of adult prompts (number of turns). Results show that, over time, the participants' clause structure complexity increased through addition of phrase-internal elements such as inflections, articles, and prepositions. Use of specific grammatical elements followed the developmental stages observed in children with typical development. For all participants, the personal pronoun (first-person singular) emerged before , (third-person singular), and or (plural). Participants with the highest number of adult-child co-constructed clauses also had the highest number of well-formed clauses. The intensity of adult prompts increased as clause structures became more complex and as participants needed more support. Implications for practice and theory are discussed.
Topics: Acrocephalosyndactylia; Adolescent; Apraxias; Cerebral Palsy; Child; Communication Aids for Disabled; Dysarthria; Female; Humans; Language Development; Linguistics; Male
PubMed: 31070060
DOI: 10.1080/07434618.2019.1584642 -
Prilozi (Makedonska Akademija Na... Dec 2017We report a 10 days old newborn with brachycephaly, midfacial hypoplasia, syndactyly and broad distal phalanx of thumb and big toe. At the 20th gestational weeks an...
We report a 10 days old newborn with brachycephaly, midfacial hypoplasia, syndactyly and broad distal phalanx of thumb and big toe. At the 20th gestational weeks an enlargement of the left cerebral ventricle and malformation of the fingers of the hands and toes were noticed on a regular ultrasound examination. The aforementioned malformations were observed at birth and at the age of 11 months. The large fontal was closed; the small one was palpable at the tip of the finger. Brachycephaly was evident with high full forehead, flat occiput, and irregular craniosynostosis especially at the coronal suture. Cutaneous syndactyly was present at both hands (fingers II-V), with almost complete fusion of the second, third and fourth fingers. Distal phalanges of the thumbs were broad as well as distal hallux. There was cutaneous syndactyly of the feet. Mental development at the age of 11 months was normal. Apert syndrome is a sporadic disorder. Rarely, inheritance is autosomal dominant. Appropriate management includes surgical treatment of the syndactylies, follow up of the eventual airway compromise and hearing difficulties. This is a report of a patient identified as a newborn.
Topics: Acrocephalosyndactylia; Craniosynostoses; Female; Genetic Predisposition to Disease; Humans; Phenotype; Predictive Value of Tests; Ultrasonography, Prenatal
PubMed: 29668474
DOI: 10.2478/prilozi-2018-0016 -
Developmental Dynamics : An Official... Nov 2018Apert syndrome is characterized by craniosynostosis and bony syndactyly of the hands and feet. The cause of Apert syndrome is a single nucleotide substitution mutation...
BACKGROUND
Apert syndrome is characterized by craniosynostosis and bony syndactyly of the hands and feet. The cause of Apert syndrome is a single nucleotide substitution mutation (S252W or P253R) in fibroblast growth factor receptor 2 (FGFR2). Clinical experience suggests increased production of saliva by Apert syndrome patients, but this has not been formally investigated. FGFR2 signaling is known to regulate branching morphogenesis of the submandibular glands (SMGs). With the Apert syndrome mouse model (Ap mouse), we investigated the role of FGFR2 in SMGs and analyzed the SMG pathology of Apert syndrome.
RESULTS
Ap mice demonstrated significantly greater SMG and sublingual gland (SMG/SLG complex) mass/body weight and percentage of parenchyma per unit area of the SMG compared with control mice. Furthermore, gene expression of Fgf1, Fgf2, Fgf3, Pdgfra, Pdgfrb, Mmp2, Bmp4, Lama5, Etv5, and Dusp6 was significantly higher in the SMG/SLG complex of Ap mice. FGF3 and BMP4 exhibited altered detection patterns. The numbers of macrophages were significantly greater in SMGs of Ap mice than in controls. Regarding functional evaluations of the salivary glands, no significant differences were observed.
CONCLUSIONS
These results suggest that the gain-of-function mutation in FGFR2 in the SMGs of Ap mice enhances branching morphogenesis. Developmental Dynamics 247:1175-1185, 2018. © 2018 Wiley Periodicals, Inc.
Topics: Acrocephalosyndactylia; Animals; Bone Morphogenetic Protein 4; Cell Count; Disease Models, Animal; Fibroblast Growth Factor 3; Gain of Function Mutation; Macrophages; Mice; Morphogenesis; Receptor, Fibroblast Growth Factor, Type 2; Submandibular Gland
PubMed: 30251381
DOI: 10.1002/dvdy.24673 -
ELife Oct 2018Cranial sutures separate the skull bones and house stem cells for bone growth and repair. In Saethre-Chotzen syndrome, mutations in or ablate a specific suture, the...
Cranial sutures separate the skull bones and house stem cells for bone growth and repair. In Saethre-Chotzen syndrome, mutations in or ablate a specific suture, the coronal. This suture forms at a neural-crest/mesoderm interface in mammals and a mesoderm/mesoderm interface in zebrafish. Despite this difference, we show that combinatorial loss of and homologs in zebrafish also results in specific loss of the coronal suture. Sequential bone staining reveals an initial, directional acceleration of bone production in the mutant skull, with subsequent localized stalling of bone growth prefiguring coronal suture loss. Mouse genetics further reveal requirements for and in both the frontal and parietal bones for suture patency, and to maintain putative progenitors in the coronal region. These findings reveal conservation of coronal suture formation despite evolutionary shifts in embryonic origins, and suggest that the coronal suture might be especially susceptible to imbalances in progenitor maintenance and osteoblast differentiation.
Topics: Acrocephalosyndactylia; Animals; Basic Helix-Loop-Helix Transcription Factors; Bone Development; Craniosynostoses; Disease Models, Animal; Gene Expression Regulation, Developmental; Gene Knockout Techniques; Humans; Mice; Mutation; Neural Crest; Osteogenesis; Twist-Related Protein 1; Zebrafish
PubMed: 30375332
DOI: 10.7554/eLife.37024 -
Medicina Oral, Patologia Oral Y Cirugia... Jan 2015Pfeiffer syndrome (PS) is mainly characterized by craniosysnostosis, midface hypoplasia, great toes with partial syndactyly of the digits, broad and medially deviated...
Pfeiffer syndrome (PS) is mainly characterized by craniosysnostosis, midface hypoplasia, great toes with partial syndactyly of the digits, broad and medially deviated thumbs. It is caused by allelic mutations in the fibroblast growth factor receptor 1 and 2 (FGFR1 and 2) genes. This study describes the clinical and genetic features of five Brazilian families affected by PS. All patients exhibited the classical phenotypes related to PS. The genetic analysis was able to detect the mutations Cys278Phe, Cys342Arg, and Val359Leu in three of these families. Two mutations were de novo, with one familial. We identified pathogenic mutations in four PS cases in five Brazilian families by PCR sequencing of FGFR1 exon 5 and FGFR2 exons 5, 8, 10, 11, 15, and 16. The clinical and genetic aspects of these families confirm that this syndrome can be clinically variable, with different mutations in the FGFR2 responsible for PS.
Topics: Acrocephalosyndactylia; Adolescent; Adult; Brazil; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Mutation; Pedigree; Phenotype
PubMed: 25129254
DOI: 10.4317/medoral.20032 -
European Journal of Orthodontics May 2022To determine whether dental maturity (dental development) was delayed in patients with Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis,...
OBJECTIVES
To determine whether dental maturity (dental development) was delayed in patients with Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis, compared with a Dutch control group without syndromes.
MATERIALS AND METHODS
This study included 60 patients (38 patients with Muenke syndrome, 17 patients with Saethre-Chotzen syndrome, and 5 with TCF12-related craniosynostosis), aged 5.8-16.8 years that were treated at the Department of Oral Maxillofacial Surgery, Special Dental Care, and Orthodontics, in Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, the Netherlands. Dental age was calculated according to Demirjian's index of dental maturity. The control group included 451 children without a syndrome.
RESULTS
Compared with the control group, dental development was delayed by an average of one year in 5- to 8-year-old patients with Muenke syndrome (P = 0.007) and in 8- to 10-year-old patients with Saethre-Chotzen syndrome (P = 0.044), but not in patients with TCF12-related craniosynostosis.
CONCLUSIONS
Our results indicated that dental development was delayed by one year, on average, in patients with Muenke syndrome and Saethre-Chotzen syndrome, compared with a Dutch control group without syndromes.
IMPLICATIONS
Our findings have improved the understanding of dental development in patients with Muenke and Saethre-Chotzen syndrome. These results can provide guidance on whether the orthodontist needs to consider growth disturbances related to dental development.
Topics: Acrocephalosyndactylia; Basic Helix-Loop-Helix Transcription Factors; Child; Child, Preschool; Craniosynostoses; Humans; Netherlands; Syndrome
PubMed: 34424951
DOI: 10.1093/ejo/cjab056 -
Arquivos de Neuro-psiquiatria Dec 2017To characterize patients with syndromic craniosynostosis with respect to their neuropsycholinguistic abilities and to present these findings together with the brain...
OBJECTIVE
To characterize patients with syndromic craniosynostosis with respect to their neuropsycholinguistic abilities and to present these findings together with the brain abnormalities.
METHODS
Eighteen patients with a diagnosis of syndromic craniosynostosis were studied. Eight patients had Apert syndrome and 10 had Crouzon syndrome. They were submitted to phonological evaluation, neuropsychological evaluation and magnetic resonance imaging of the brain. The phonological evaluation was done by behavioral observation of the language, the Peabody test, Token test and a school achievement test. The neuropsychological evaluation included the WISC III and WAIS tests.
RESULTS
Abnormalities in language abilities were observed and the school achievement test showed abnormalities in 66.67% of the patients. A normal intelligence quotient was observed in 39.3% of the patients, and congenital abnormalities of the central nervous system were observed in 46.4% of the patients.
CONCLUSION
Abnormalities of language abilities were observed in the majority of patients with syndromic craniosynostosis, and low cognitive performance was also observed.
Topics: Acrocephalosyndactylia; Adolescent; Adult; Child; Child, Preschool; Craniofacial Dysostosis; Female; Humans; Language Development; Language Tests; Male; Neuropsychological Tests; Young Adult
PubMed: 29236889
DOI: 10.1590/0004-282X20170171 -
Prilozi (Makedonska Akademija Na... Mar 2017Prematurely fused metopic suture results in developmental anomaly named trigonocephaly. The treatment of trigonocephaly is a surgical reconstruction, starting from the...
INTRODUCTION
Prematurely fused metopic suture results in developmental anomaly named trigonocephaly. The treatment of trigonocephaly is a surgical reconstruction, starting from the simple suturectomy toward the complicated cranial vault reconstructions with aim to obtain enough endocranial space for normal development of the brain and aesthetic correction as well.
THE AIM
The aim of our paper is to present our experience on this pathology in the Republic of Macedonia, stressing the trigonocephaly as one of the rare forms of craniosynostosis. Our material: During a period of 20 years (from 1996 to 2015) at the Pediatric department of the Clinic for Neurosurgery in Skopje, we observed 18 babies with trigonocephaly, including one with Carpenter syndrome and trigonocephaly, 14 males and 4 females. All children had simple trigonocephaly, one had syndromic trigonocephaly (Carpenter's syndrome). According to Oi and Matsumoto classification done in 19865 severe trigonocephaly is observed in 11 cases and, moderate trigonocephaly in 7 cases. Our method: Our treatment consisted of slightly modified Di Rocco's3 surgical procedure named "shell" operation, adding transposition of the "bone flap".
RESULTS
The postoperative period was uneventful except for the expected forehead swelling. The babies were discharged from the hospital on average at the 8th postoperative day. At the three months control after the surgery, the head had excellent aesthetic appearance, with regular psychomotor development according to the age of the patient (Fig 3а and 3b). We had no serious complications except the expected postoperative swelling of the forehead. All operated children had excellent "long term" aesthetic effect and normal psychomotor development.
CONCLUSION
The early recognition of these anomalies including all craniosynostoses, the deformities of the newborn and infant's head and the preventive operative reconstruction would prevent abnormal disturbance of the psychomotor development during the child's growth. The multidisciplinary approach can prevent new disabled individuals in the society. Our technique allows shortening the entire surgical procedure, especially in the departments where blood saving devices are not available.
Topics: Acrocephalosyndactylia; Age Factors; Child Development; Cranial Sutures; Craniosynostoses; Female; Humans; Infant; Infant, Newborn; Male; Neurosurgical Procedures; Postoperative Complications; Plastic Surgery Procedures; Republic of North Macedonia; Time Factors; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 28593893
DOI: 10.1515/prilozi-2017-0004