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BMJ Case Reports Mar 2022The management of patients with Apert syndrome (AS) is complex and reflects the multisystem disease as a result of premature fusion of cranial vault, cranial base and...
The management of patients with Apert syndrome (AS) is complex and reflects the multisystem disease as a result of premature fusion of cranial vault, cranial base and midface sutures as well as extremity anomalies characterised by syndactyly. Early cranial sutural fusion results in craniocerebral disproportion which can lead to crisis surgical intervention due to raised intracranial pressure, ophthalmic and compromised airway concerns. Childhood inventions are often determined by psychosocial concerns and adult surgical interventions are often determined by cosmetic concerns. Treatments are provided by many different specialists within multidisciplinary teams (MDT). The treatment pathway extends from birth well into adulthood and is often associated with a heavy burden of care. Due to the extensive nature of the interaction with these patients MDT members have opportunities to provide enhanced patient-centred care and support.This case report provides an overview of the current knowledge of the aetiology of AS, illustrates the pathway of surgical and non-surgical management of AS and provides a long-term review of the dentofacial treatment outcomes.By having a better understanding of the impact of AS and treatment provided, MDT members can not only provide improved clinical treatment but also offer improved patient experiences for those with craniofacial anomalies, in particular, an increased awareness of the psychosocial challenges they endure.
Topics: Acrocephalosyndactylia; Adult; Child; Cranial Sutures; Craniofacial Abnormalities; Face; Humans; Skull Base
PubMed: 35236672
DOI: 10.1136/bcr-2021-245224 -
Molecular Genetics & Genomic Medicine Apr 2022Craniosynostosis is the result of the early fusion of cranial sutures. Syndromic craniosynostosis includes but not limited by Crouzon syndrome and Pfeiffer syndrome....
OBJECTIVE
Craniosynostosis is the result of the early fusion of cranial sutures. Syndromic craniosynostosis includes but not limited by Crouzon syndrome and Pfeiffer syndrome. Considerable phenotypic overlap exists among these syndromes and mutations in FGFR2 may cause different syndromes. This study aims to investigate the explanation of the phenotypic variability via clinical and genetic evaluation for eight patients in a large pedigree.
METHODS
For each patient, comprehensive physical examination, cranial plain CT scan with three-dimensional CT reconstruction (3D-CT), and eye examinations were conducted. Whole exome sequencing was applied for genetic diagnosis of the proband. Variants were analyzed and interpreted following the ACMG/AMP guidelines. Sanger sequencing was performed to reveal genotypes of all the family members.
RESULTS
A pathogenic variant in the FGFR2 gene, c.833G > T (p.C278F), was identified and proved to be co-segregate with the disease. Some symptoms of head, hearing, vision, mouth, teeth expressed differently by affected individuals. Nonetheless, all the eight patients manifested core symptoms of Crouzon syndrome without abnormality in the limbs, which could exclude diagnosis of Pfeiffer syndrome.
CONCLUSION
We have established clinical and genetic diagnosis of Crouzon syndrome for eight patients in a five-generation Chinese family. Variability of clinical features among these familial patients was slighter than that in previously reported sporadic cases.
Topics: Acrocephalosyndactylia; Biological Variation, Population; Craniofacial Dysostosis; Craniosynostoses; Humans; Receptor, Fibroblast Growth Factor, Type 2; Syndrome
PubMed: 35235708
DOI: 10.1002/mgg3.1901 -
The Journal of Contemporary Dental... Oct 2021To present an Apert syndrome patient with midfacial growth deficiency treated with Le Fort III distraction osteogenesis and subsequent two-jaw surgery.
AIM AND OBJECTIVE
To present an Apert syndrome patient with midfacial growth deficiency treated with Le Fort III distraction osteogenesis and subsequent two-jaw surgery.
BACKGROUND
Apert syndrome is expressed as a severe and irregular craniosynostosis, midfacial hypoplasia, and symmetric syndactyly in the fingers and toes. For craniosynostosis syndromes, treatment planning is complex due to the disharmony between facial profile and occlusion.
CASE DESCRIPTION
A 4-year-and-5-month-old boy, diagnosed with Apert syndrome, showed a concave profile accompanied with midfacial hypoplasia, moderate exorbitism, a reversed occlusion of -10.0 mm, an anterior open bite of -5.0 mm, and skeletal class III jaw-base relationship. The patient, aged 15 years and 4 months, underwent a Le Fort III osteotomy, and subsequent osteodistraction was performed via a rigid external distraction (RED) device. His midfacial bone was advanced by approximately 7.0 mm. One year after the distraction, preoperative treatment with 0.018-in preadjusted edgewise appliances was initiated. Two-jaw surgery with a Le Fort I osteotomy and bilateral sagittal split ramus osteotomy was performed after 42 months of preoperative orthodontic treatment. At the age of 20 years and 9 months, his facial profile dramatically changed to a straight profile, and an acceptable occlusion with an adequate interincisal relationship was obtained. A functional occlusion with an excellent facial profile was maintained throughout the 2-year retention period, although the upper dental arch width was slightly decreased, resulting in the recurrence of the left posterior crossbite.
CONCLUSION
Our report indicates the necessity of long-term follow-up in patients with craniosynostosis because of syndrome-specific growth and methodologically induced relapse.
CLINICAL SIGNIFICANCE
The two-stage operation combining early distraction osteogenesis and postgrowth orthognathic surgery proves to be an effective therapy for correcting midfacial hypoplasia and skeletal mandibular protrusion caused by Apert syndrome.
Topics: Acrocephalosyndactylia; Adolescent; Adult; Cephalometry; Humans; Infant; Male; Open Bite; Osteogenesis, Distraction; Osteotomy, Le Fort; Young Adult
PubMed: 35197388
DOI: No ID Found -
World Neurosurgery May 2022In patients with Pfeiffer syndrome, several corrections are required to correct facial retrusion, maxillary deficiency, or even hypertelorism. The frontofacial monobloc...
BACKGROUND
In patients with Pfeiffer syndrome, several corrections are required to correct facial retrusion, maxillary deficiency, or even hypertelorism. The frontofacial monobloc advancement (FFMA) and the facial bipartition (FB) are the gold standard surgeries. We present the correction of this deformity using a simultaneous computer-assisted FFMA and FB.
METHODS
The 3-dimensional surgical planning defined the virtual correction and bone-cutting guide in view of the FFMA and FB. Coronal and intraoral approaches were combined to perform the osteotomies. Four internal distractors were also placed for the postoperative distraction osteogenesis.
RESULTS
We reported 2 cases of computer-assisted surgery with satisfying outcomes. The sagittal deficiency (fronto-facial retrusion) was corrected by FFMA and the transversal abnormality (i.e., hypertelorism and maxillary deficiency) by the FB, then followed by an internal distraction osteogenesis.
CONCLUSIONS
Computer-assisted surgery is helpful and a reliable option for the management of complex faciocraniosynostosis such as hypertelorism and frontofacial retrusion.
Topics: Acrocephalosyndactylia; Computers; Face; Humans; Hypertelorism; Osteotomy
PubMed: 35176524
DOI: 10.1016/j.wneu.2022.02.031 -
Plastic and Reconstructive Surgery Apr 2022Visual impairment secondary to orbital and periorbital dysmorphology is frequent in Pfeiffer syndrome patients. The etiopathogenesis of this aberrancy, however, remains...
BACKGROUND
Visual impairment secondary to orbital and periorbital dysmorphology is frequent in Pfeiffer syndrome patients. The etiopathogenesis of this aberrancy, however, remains unclear.
METHODS
Untreated Pfeiffer syndrome patients (n = 31) and normal control subjects (n = 43) were compared. Craniometric and volumetric analyses related to the orbital and periorbital anatomy were performed using Materialise (Leuven, Belgium) software.
RESULTS
Overall, orbital cavity volume of Pfeiffer patients is reduced by 28 percent (p < 0.001), compared to normal, starting before 3 months of age (p = 0.004). Globe volume was diminished by 10 percent (p = 0.041) before 3 months of age, yet tended to catch up thereafter. However, the retrobulbar soft-tissue volume remained smaller beyond 1 year of age (17 percent, p = 0.003). Globe volume projection beyond the bony orbit increased in all observed ages (82 percent, p < 0.001). The volumes of sphenoid bone, maxilla, and mandible proportionately were restricted by 24 to 25 percent (p = 0.003 to 0.035) before 3 months of age. The volume of maxilla and mandible gradually approximate normal; however, the sphenoid bone volume in Pfeiffer patients remains less than normal (p = 0.002) into childhood. The anteroposterior length of both the zygoma and the maxilla was reduced by 14 percent (p < 0.001). Anterior positioning of the zygoma is less by 23 percent (p < 0.001) in Pfeiffer patients overall, with anterior positioning of maxilla reduced similarly by 23 percent (p < 0.001).
CONCLUSIONS
Pfeiffer syndrome patients develop decreased retrobulbar soft-tissue and globe volume, along with a restricted orbital cavity volume in infancy. Significant hypoplasia of the sphenoid bone is associated with more severe central facial (maxilla) retrusion, compared to lateral facial structures (zygoma).
CLINICAL QUESTION/LEVEL OF EVIDENCE
Risk, II.
Topics: Acrocephalosyndactylia; Cephalometry; Child; Humans; Maxilla; Orbit; Zygoma
PubMed: 35171849
DOI: 10.1097/PRS.0000000000008928 -
Plastic and Reconstructive Surgery Apr 2022The thumbs of patients with Apert syndrome are characteristically short and radially deviated, contributing to functional hand impairment. The authors report a...
BACKGROUND
The thumbs of patients with Apert syndrome are characteristically short and radially deviated, contributing to functional hand impairment. The authors report a two-staged technique for distraction lengthening of the Apert thumb using a robust cohort of pediatric patients.
METHODS
The authors retrospectively reviewed medical records of pediatric patients with Apert syndrome who underwent thumb distraction lengthening between 1999 and 2019. The technique was two-staged: (1) application of uniplanar distractor and phalangeal osteotomy, followed by (2) distractor removal, bone grafting, and fixation. Clinical records, preoperative and postoperative radiographs, and photographs were reviewed.
RESULTS
Twenty-two patients (41 thumbs) with Apert syndrome were identified and treated (mean age at initial distraction, 11.5 years). A mean distraction gap of 31.3 mm was achieved over a median time of 40.0 days. The mean healing index was 26.3 days per centimeter. The thumbnail complex was lengthened a median length of 3.0 mm. The median follow-up time was 5.0 years, with complications occurring in 36.4 percent (eight out of 22) of patients. A delayed bone union occurred in one patient, and rotational malunion occurred in one patient.
CONCLUSION
Although long-term outcomes data are needed, thumb distraction lengthening following syndactyly release in patients with Apert syndrome is safe and should be considered to augment the overall appearance and functionality of the hand.
CLINICAL QUESTION/LEVEL OF EVIDENCE
Therapeutic, IV.
Topics: Acrocephalosyndactylia; Child; Finger Phalanges; Hand; Humans; Osteogenesis, Distraction; Retrospective Studies; Thumb
PubMed: 35157629
DOI: 10.1097/PRS.0000000000008929 -
The Journal of Craniofacial Surgery Sep 2022
Topics: Acrocephalosyndactylia; Animals; Child, Preschool; Hand Deformities, Congenital; Humans; Plastic Surgery Procedures; Skin; Skin Transplantation; Tilapia
PubMed: 35148527
DOI: 10.1097/SCS.0000000000008522 -
Journal of Cellular Physiology Apr 2022The fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling pathway plays important roles in the development and growth of the skeleton. Apert syndrome caused by...
The fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling pathway plays important roles in the development and growth of the skeleton. Apert syndrome caused by gain-of-function mutations of FGFR2 results in aberrant phenotypes of the skull, midface, and limbs. Although short limbs are representative features in patients with Apert syndrome, the causative mechanism for this limb defect has not been elucidated. Here we quantitatively confirmed decreases in the bone length, bone mineral density, and bone thickness in the Apert syndrome model of gene knock-in Fgfr2 (EIIA-Fgfr2 ) mice. Interestingly, despite these bone defects, histological analysis showed that the endochondral ossification process in the mutant mice was similar to that in wild-type mice. Tartrate-resistant acid phosphatase staining revealed that trabecular bone loss in mutant mice was associated with excessive osteoclast activity despite accelerated osteogenic differentiation. We investigated the osteoblast-osteoclast interaction and found that the increase in osteoclast activity was due to an increase in the Rankl level of osteoblasts in mutant mice and not enhanced osteoclastogenesis driven by the activation of FGFR2 signaling in bone marrow-derived macrophages. Consistently, Col1a1-Fgfr2 mice, which had osteoblast-specific expression of Fgfr2 S252W, showed significant bone loss with a reduction of the bone length and excessive activity of osteoclasts was observed in the mutant mice. Taken together, the present study demonstrates that the imbalance in osteoblast and osteoclast coupling by abnormally increased Rankl expression in Fgfr2 mutant osteoblasts is a major causative mechanism for bone loss and short long bones in Fgfr2 mice.
Topics: Acrocephalosyndactylia; Animals; Cell Differentiation; Gene Knock-In Techniques; Humans; Mice; Osteoblasts; Osteoclasts; Osteogenesis; RANK Ligand; Receptor, Fibroblast Growth Factor, Type 2; Skull
PubMed: 35048384
DOI: 10.1002/jcp.30682 -
The Cleft Palate-craniofacial Journal :... Apr 2023To date, limited research has been carried out into the psychological impact of having a diagnosis of Apert syndrome (AS) and the life experiences of families living...
To date, limited research has been carried out into the psychological impact of having a diagnosis of Apert syndrome (AS) and the life experiences of families living with this condition. The aim of the current study was to explore psychological adjustment to AS from the perspectives of young people, and their parents, with the broader goal of informing care, and support for this population. Four young people (2 male) aged 11 to 15 years and their mothers were interviewed in their homes using a semistructured interview guide and photo-elicitation methods. Transcripts were analyzed using Interpretive Phenomenological Analysis. Three superordinate themes were identified from the data: (1) Acceptance and Adjustment: A Cyclical Journey; (2) A Barrier to Adjustment: Navigating Treatment; and (3) Facilitating Adjustment: Social Support. Families described adjustment as a cyclical process, which was sensitive to change, particularly in the context of ongoing medical treatment. Families also utilized many resources, particularly in the form of social support, to adjust to the challenges of AS and build resilience. The findings of this study have important implications for the implementation of patient-centered care within designated craniofacial treatment centers, which should at a minimum include the provision of reliable information throughout the treatment pathway, additional support from health professionals at key times of transition, and the coordination of support across medical teams, and other key organizations in the child's life.
Topics: Child; Female; Humans; Male; Adolescent; Emotional Adjustment; Acrocephalosyndactylia; Parents; Social Support; Mothers
PubMed: 34967688
DOI: 10.1177/10556656211069817 -
Plastic and Reconstructive Surgery Jan 2022The haploinsufficiency in the TWIST1 gene encoding a basic helix-loop-helix transcription factor is a cause of one of the craniosynostosis syndromes, Saethre-Chotzen...
BACKGROUND
The haploinsufficiency in the TWIST1 gene encoding a basic helix-loop-helix transcription factor is a cause of one of the craniosynostosis syndromes, Saethre-Chotzen syndrome. Patients with craniosynostosis usually require operative release of affected sutures, which makes it difficult to observe the long-term consequence of suture fusion on craniofacial growth.
METHODS
In this study, we performed quantitative analysis of morphologic changes of the skull in Twist1 heterozygously-deleted mice (Twist1+/-) with micro-computed tomographic images.
RESULTS
In Twist1+/- mice, fusion of the coronal suture began before postnatal day 14 and progressed until postnatal day 56, during which morphologic changes occurred. The growth of the skull was not achieved by a constant increase in the measured distances in wild type mice; some distances in the top-basal axis were decreased during the observation period. In the Twist1+/- mouse, growth in the top-basal axis was accelerated and that of the frontal cranium was reduced. In the unicoronal suture fusion mouse, the length of the zygomatic arch of affected side was shorter in the Twist1+/- mouse. In one postnatal day 56 Twist1+/- mouse with bilateral coronal suture fusion, asymmetric zygomatic arch length was identified.
CONCLUSION
The authors'results suggest that measuring the length of the left and right zygomatic arches may be useful for early diagnosis of coronal suture fusion and for estimation of the timing of synostosis, and that more detailed study on the growth pattern of the normal and the synostosed skull could provide prediction of the risk of resynostosis.
CLINICAL RELEVANCE STATEMENT
The data from this study can be useful to better understand the cranial growth pattern in patients with craniosynostosis.
Topics: Acrocephalosyndactylia; Animals; Cranial Sutures; Disease Models, Animal; Female; Frontal Bone; Gene Expression Regulation, Developmental; Heterozygote; Humans; Male; Mice; Mice, Transgenic; Mutation; Twist-Related Protein 1; X-Ray Microtomography; Zygoma
PubMed: 34936613
DOI: 10.1097/PRS.0000000000008665