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The Journal of Craniofacial Surgery 2019Complicated craniofacial malformations interfacing with multiple intracellular regulatory mechanisms, lead to ambiguous growth patterns in Apert syndrome. This study...
Complicated craniofacial malformations interfacing with multiple intracellular regulatory mechanisms, lead to ambiguous growth patterns in Apert syndrome. This study aims to explore the chronology and pathogenesis of the development of craniofacial anatomic relationships and to verify the positional correlates between skull and facial structures in Apert syndrome. Fifty-four computed tomography scans (Apert, n = 18; control, n = 36) were included and divided into 3 age subgroups. Craniofacial 3-dimensional cephalometries were analyzed by Materialize software. The angle between sella-nasion plane and maxillary plane widens 7.74° (P = 0.003) prior to 6 months of age; thereafter, this widening increases by 10.36° (P < 0.001) in 6 months to 2 years of age, and remains increased by 8.9° (P = 0.046) throughout childhood. The angle between Frankfort horizontal plane and maxillary plane widens 5.17° (P = 0.022) before 6 months. Angles SNA, SNB, and ANB showed decreases, averaging 12.23° (P < 0.001), 5.19° (P = 0.004), and 6.72° (P = 0.001), respectively. The linear measurements showed synchronicity and continuing deformity into adulthood. Between 6 months to 2 years of age, the distance from sella to nasion (S-N), anterior nasal spine (S-ANS), and posterior nasal spine (S-PNS) decreased 8% (P = 0.006), 16% (P < 0.001), and 19% (P = 0.002), respectively, and remained shortened into adulthood. The angulation changes occur earlier in development than linear distance reduction in Apert syndrome patients compared with controls. Angular adjustments were not sufficient to maintain normal cranial base length. Facial deformity of Apert syndrome temporally begins with the midface, and affects orbit and mandible later in life.
Topics: Acrocephalosyndactylia; Cephalometry; Child, Preschool; Face; Humans; Infant; Skull; Tomography, X-Ray Computed
PubMed: 30358751
DOI: 10.1097/SCS.0000000000004836 -
Child's Nervous System : ChNS :... Jun 2018Apert syndrome is one of the most common craniosynostosis syndrome caused by mutation in genes encoding fibroblast growth factor receptor 2 (FGFR2). Craniosynostosis,...
BACKGROUND
Apert syndrome is one of the most common craniosynostosis syndrome caused by mutation in genes encoding fibroblast growth factor receptor 2 (FGFR2). Craniosynostosis, midfacial hypoplasia, and syndactyly/symphalangism are features of this syndrome. Sturge-Weber syndrome (SWS) on the other hand is a congenital neurocutaneous disorder characterized by facial port-wine stains (PWSs) and leptomeningeal vascular capillary malformations. In 2013, the causative mutation underlying SWS (p.R183Q somatic activating mutation in the guanine nucleotide-binding protein alpha-q (GNAQ) gene) was identified. This mutation increases downstream signaling along the RAS/MAPK pathway, resulting in increased cell proliferation. The interaction between FGFR and the RAS/MAPK signaling pathway was proposed in recent years. Elevated synthesis of fibronectin in the calvaria of patients with Apert syndrome and increased fibronectin gene expression in port wine-derived fibroblasts of patients with Sturge-Weber disease have also been reported.
CASE PRESENTATION
We report a unique case of Apert and Sturge-Weber syndromes occurring in the same patient. The child was noted to demonstrate features suggestive of Apert syndrome at birth, including brachycephaly, midface hypoplasia, and syndactyly. In addition, a left-sided facial port wine stain in the forehead was noted. Magnetic resonance imaging (MRI) of the brain was performed and confirmed the diagnosis of Sturge-Weber syndrome by demonstrating the presence of left sided leptomeningeal vascular capillary malformation and left-sided cerebral hemiatrophy.
CONCLUSION
To the best of our knowledge, there has been no prior described case of Apert and Sturge-Weber syndromes occurring in the same patient. This case report identifies an area of potential research on fibronectin and derangement of the RAS/MAPK signaling pathway in relation to Apert syndrome and Sturge-Weber syndrome. In view of the rare concurrence of Apert and Sturge-Weber syndromes, the underlying pathogenesis is thought to be multifactorial, one of which may be related to either increased fibronectin gene expression or derangement of the RAS/MAPK signaling pathway.
Topics: Acrocephalosyndactylia; Fibronectins; Humans; Infant, Newborn; MAP Kinase Signaling System; Sturge-Weber Syndrome; ras Proteins
PubMed: 29476210
DOI: 10.1007/s00381-018-3758-1 -
The Journal of Craniofacial Surgery Jan 2016The management of the airway in Apert syndrome is complex and multidisciplinary. This rare syndrome, occurring in up to approximately 1 in 65,000 live births, results in...
The management of the airway in Apert syndrome is complex and multidisciplinary. This rare syndrome, occurring in up to approximately 1 in 65,000 live births, results in airway compromise at various anatomic levels, in addition to abnormal central respiratory drive. Obstructive apneas arise because of decreased airway caliber, which may occur in the form of congenital bony nasal stenosis, choanal atresia, a deviated nasal septum, a narrowed nasopharynx, a thick long soft palate, lateral palatal swellings, and a tracheal cartilage sleeve. Central apneas in Apert syndrome arise because of raised intracranial pressure and/or Chiari malformations. The purpose of this study was to investigate our treatment methods and outcomes in optimizing the airway in this complex, rare and interesting cohort of patients who present with airway compromise. Patients with Apert syndrome were retrospectively evaluated during a period from 1990 to 2013. Treatments for obstructive apnea were dilatation of nasal airways and choanal atresia repair, adenoidectomy, tonsillectomy, early midface advancement, and noninvasive ventilation. The insertion of ventriculoperitoneal shunts, fronto-orbital advancement, and Chiari decompression aid in managing central apneas. The authors present our experience at Alder Hey Children's Hospital, Liverpool, one of the 4 Supraregional Craniofacial Units in the United Kingdom.
Topics: Acrocephalosyndactylia; Adenoidectomy; Adolescent; Airway Management; Child; Child, Preschool; Choanal Atresia; Cleft Palate; Cohort Studies; Decompression, Surgical; Dilatation; Female; Follow-Up Studies; Frontal Bone; Humans; Infant; Infant, Newborn; Male; Nasal Obstruction; Orbit; Respiration, Artificial; Retrospective Studies; Sleep Apnea, Obstructive; Tonsillectomy; Trachea; Treatment Outcome; Ventriculoperitoneal Shunt; Young Adult
PubMed: 26674912
DOI: 10.1097/SCS.0000000000002333 -
The Journal of Craniofacial Surgery Jan 1996Apert's syndrome is a malformation characterized by abnormalities in the cranial vault, midfacial malformations, and syndactylia. The present study analyzes the lateral... (Review)
Review
Apert's syndrome is a malformation characterized by abnormalities in the cranial vault, midfacial malformations, and syndactylia. The present study analyzes the lateral and frontal projections of the teleradiograms from five patients. Data were taken on the skeletal features and an attempt was made to interpret them in terms of functional matrices. We have used cephalometry as a descriptive device although the intent was also to use it to provide a perspective on the pathogenetic data derived from the literature. The hypothesis analyzed is that from the outset of craniofacial pathogenesis there may be a primitive alteration of the cartilaginous template from which are derived endochondral bones. The progressive involvement of the synchondrosis of the cranial base is subsequently transmitted to the membranous structures of the vault and face through the coronal ring and lambdoid suture systems. Although the data gained do not actually confirm this hypothesis, they do provide further support for it.
Topics: Acrocephalosyndactylia; Adolescent; Cephalometry; Child; Female; Humans; Male; Mandible; Maxilla; Nasopharynx; Orbit; Radiography; Skull; Skull Base
PubMed: 9086898
DOI: No ID Found -
The Cleft Palate-craniofacial Journal :... Nov 2014Purpose : Developing teeth are used to assess maturity and estimate age in a number of disciplines. The purpose of this investigation was to study the dental maturation...
Purpose : Developing teeth are used to assess maturity and estimate age in a number of disciplines. The purpose of this investigation was to study the dental maturation in children with Crouzon or Apert syndrome compared with nonsyndromic controls. Patients and Methods : Records of 40 children with Crouzon syndrome (18 boys and 22 girls, aged 4.0 to 17.9 years) and 28 children with Apert syndrome (10 boys and 18 girls, aged 3.9 to 15.1 years) were referred to the Department of Orthodontics, Cleft Palate Team and Craniofacial Team, Erasmus MC-Sophia. Data from syndromic children were compared with data from 451 nonsyndromic children (225 boys and 226 girls, aged 2.9 to 16.9 years). From panoramic radiographs, dental maturation was determined for patients with Crouzon and Apert syndromes and compared with data collected from control children. Logistic functions were constructed for dental maturation over time for syndromes and gender. Results : Statistically significant gender differences in dental maturation scores were found for girls with Crouzon (P < .05) and Apert syndrome (P < .05). Patients with Apert syndrome demonstrated a significantly delayed dental maturation (P < .05), while patients with Crouzon syndrome showed a nonsignificant delay. Conclusions : Dental maturation in patients with Apert syndrome was more delayed than in patients with Crouzon syndrome. The delay of tooth formation in patients with Crouzon or Apert syndrome suggests a possible common genetic association.
Topics: Acrocephalosyndactylia; Adolescent; Case-Control Studies; Child; Child, Preschool; Craniofacial Dysostosis; Female; Humans; Male; Odontogenesis; Radiography, Panoramic
PubMed: 24021057
DOI: 10.1597/13-071 -
Fetal and Pediatric Pathology Dec 2012Apert syndrome (Acrocephalosyndactyly type I; AS) is a rare but well-known autosomal dominant disorder characterized by craniosynostosis, midface hypoplasia,...
Apert syndrome (Acrocephalosyndactyly type I; AS) is a rare but well-known autosomal dominant disorder characterized by craniosynostosis, midface hypoplasia, bony/cutaneous syndactyly of fingers and toes as well as a variety of associated congenital anomalies involving the brain, heart, limbs and other organ systems. We report the case of a fetus with molecularly confirmed Apert syndrome and additional fusion of the thalamic nuclei. Various central nervous system anomalies, have been reported in patients with AS. However, as far as we know cases of fused thalami in Apert syndrome have never been reported so far.
Topics: Abnormalities, Multiple; Abortion, Eugenic; Acrocephalosyndactylia; Adult; DNA Mutational Analysis; Fatal Outcome; Female; Gestational Age; Humans; Mutation; Nuchal Translucency Measurement; Pregnancy; Receptor, Fibroblast Growth Factor, Type 2; Thalamus; Ultrasonography, Prenatal
PubMed: 22443264
DOI: 10.3109/15513815.2012.659407 -
Plastic and Reconstructive Surgery Jan 2013The authors catalogued phenotypic variability among children with Apert syndrome, reviewed surgical outcomes (particularly with respect to their treatment goals of...
BACKGROUND
The authors catalogued phenotypic variability among children with Apert syndrome, reviewed surgical outcomes (particularly with respect to their treatment goals of avoiding preventable developmental delays and reducing operative interventions), and examined correlations that might stimulate improved treatment paradigms.
METHODS
A case series review of all Apert syndrome patients, treated by a single surgeon, including phenotypic variations, mutational analyses, developmental assessments, and surgical treatments, was performed.
RESULTS
Over a 20-year period, 135 Apert syndrome patients were treated (32 percent from birth). A fairly even distribution of mutations was noted (S252W, n = 20; P253R, n = 18). Of 268 hands, 60 percent were type I, 21 percent were type II, and 19 percent were type III. Fifty percent had palatal anomalies. Three separate skull configuration types were identified, and 29 percent had acquired Chiari malformations, 24 percent had anomalies of the septum pellucidum, and 12 percent had anomalies of the corpus callosum. Cranial and midfacial procedures were performed significantly earlier at outside centers (6.2 months versus 12.6 months, and 5.3 years versus 7.5 years). No significant correlations were noted between development and gene mutation, hand or skull phenotypes, intracranial anomalies, and timing of initial skull surgery. A significant correlation was noted between adverse development and ventriculoperitoneal shunts, tracheostomies, and more operative interventions. Higher development strongly correlated with treatment at our center from birth.
CONCLUSION
Treatment goals focused on the prevention of avoidable developmental delays (from raised intracranial pressure and sleep apnea) and reducing operative interventions may potentially improve developmental outcomes.
CLINICAL QUESTION/LEVEL OF EVIDENCE
Therapeutic, III.
Topics: Acrocephalosyndactylia; Adolescent; Adult; Algorithms; Child; Child, Preschool; DNA Mutational Analysis; Decision Support Techniques; Developmental Disabilities; Genetic Markers; Humans; Infant; Orthopedic Procedures; Phenotype; Receptor, Fibroblast Growth Factor, Type 2; Reoperation; Retrospective Studies; Treatment Outcome; Young Adult
PubMed: 23271523
DOI: 10.1097/PRS.0b013e3182729f42 -
Brazilian Journal of Otorhinolaryngology 2008
Review
Topics: Acrocephalosyndactylia; Humans; Male; Young Adult
PubMed: 18853000
DOI: 10.1016/s1808-8694(15)30621-2 -
BMJ Case Reports Jul 2018Apert syndrome is a rare congenital disorder characterised by craniosynostosis, midface hypoplasia and syndactyly of hands and feet. Here we present a case of a...
Apert syndrome is a rare congenital disorder characterised by craniosynostosis, midface hypoplasia and syndactyly of hands and feet. Here we present a case of a 44-year-old woman, with a genetic diagnosis of Apert syndrome from birth, who presented with symptomatic left-sided hip osteoarthritis secondary to femoral abnormalities. She proceeded to have a total hip replacement. This case report describes the rare occurrence to identify a possible association between Apert syndrome and hip abnormalities.
Topics: Acrocephalosyndactylia; Adult; Arthroplasty, Replacement, Hip; Female; Femur; Hip Dislocation; Hip Joint; Humans; Osteoarthritis, Hip
PubMed: 29973408
DOI: 10.1136/bcr-2017-221789 -
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