Apert Syndrome Research Articles

Apert Syndrome: A Case Report

Background: Apert syndrome is a type 1 acrocephalosyndactyly, a rare syndrome characterized by the presence of multiple craniosynostoses, dysmorphic facial manifestations, and syndactyly of hand and feet. It affects 1:100.00 of birth and is the second most common of syndromic craniosynostosis. Molecular genetic tests that identify the heterozygous pathogenic variant in FGFR2 genes - identical with Apert syndrome cost too high to be applicable in developing countries. Therefore, the diagnosis of Apert syndrome should be suspected from the clinical findings. Three cases from the Community of Indonesian Apert Warrior Group were collected. These series were based on medical and surgical records. We obtained the patient characteristics from the phenotypic manifestations only. Case report: We present a case of a newborn baby girl, with similar anatomical findings, such as skull shape abnormality, midface hypoplasia, intraoral disfigurement, and hands and feet deformities that resemble Apert Syndrome. Our series presents similar Apert syndrome characteristics, such as typical craniofacial dysmorphic with symmetrical syndactyly of both upper and lower extremities. These clinical findings are essential to establish an initial diagnosis of Apert Syndrome.

Syndromic Craniosynostosis: A Comprehensive Review.

Craniosynostosis is a fetal skull condition that occurs when one or multiple sutures merge prematurely. This leads to limited growth perpendicular to the fused suture, which results in compensatory growth of cranial bones parallel to it. Syndromic craniosynostosis ensues when the cranial deformity is accompanied by respiratory, neurological, cardiac, musculoskeletal, and audio-visual abnormalities. The most common syndromes are Apert, Crouzon, Pfeiffer, Muenke, and Saethre-Chotzen syndromes and craniofrontonasal syndrome. Each of these syndromes has distinct genetic mutations that contribute to their development. Mutations in genes such as FGFR, TWIST, and EFNB1 have been identified as playing a role in the development of these syndromes. Familiarity with the genetic basis of each syndrome is not only essential for identifying them but also advantageous for current pharmacological investigations. Surgical treatment is often necessary for syndromic craniosynostosis to correct the cranial deformities. Advances have been made in surgical techniques for each specific syndrome, but further research is needed to develop personalized approaches that address the unique symptoms and complications of individual patients, particularly those related to neurological and respiratory issues. This group of syndromes included in cranial synostosis presents significant educational and clinical interest due to the wide range of symptoms and the variable course of the disease, especially in the last decades when crucial advances in diagnosis and treatment have been achieved, altering the prognosis as well as the quality of life of these patients. In summary, this article provides a comprehensive overview of syndromic craniosynostosis, including the genetic mutations associated with each syndrome and the surgical treatment options available.

Revisiting Radiographic Characteristic of the Hands in Apert Syndrome: A Literature Review with Cases

Introduction: Syndactyly of the hand in Apert syndrome involves all components of the hands. In 1991, Joseph Upton introduced a comprehensive classification of the Apert hands based on its severity. Plain x-ray is the most commonly used to evaluate bony abnormality. Case Presentation: We present two cases with classic characteristics of Apert syndrome with demonstrated different types of Apert hands; type II and type III. Radiographs exhibited bony deformities with typical misalignment and multiple osseous formations in several parts of phalanges. Discussion: Apert hands present complex syndactylies involving the index, middle, and ring fingers in different stages regarding Upton’s classification system. Almost all Apert hands also lack the active motion of the interphalangeal joints. The ossification allowed the synostosis and symphalangism to become evident on radiographs. The abnormality of the epiphysial growth causes short and deviated fingers. Conclusion: Apert hands demonstrate complex deformity involving bony structures that developed prenatally and postnatally. Typical deformities including complex syndactyly, clinodactyly, and symphalangism.

Clinical and genetic findings of two cases with Apert syndrome

Clinical and genetic findings of two cases with Apert syndrome

De novo variants of dominant monogenic disorders in Vietnam detected by a noninvasive prenatal test: a case series.

Background: Noninvasive prenatal tests for monogenic diseases (NIPT-SGG) have recently been reported as helpful in early-stage antenatal screening. Ourstudy describes the clinical and genetic features of cases identified by NIPT-SGG. Materials & methods: In a cohort pregnancy with abnormal sonograms, affected cases were confirmed by invasive diagnostic testsconcurrently, with NIPT-SGG targeting 25 common dominant single-gene diseases. Results: A total of 13single-gene fetuses were confirmed, including Noonan and Costello syndromes, thanatophoric dysplasia, achondroplasia, osteogenesis imperfectaand Apert syndrome. Two novel variants seenwere tuberous sclerosis complex (TSC2 c.4154G>A) and Alagille syndrome (JAG1 c.3452del). Conclusion: NIPT-SGG and standard tests agreeon the results for 13 fetuses with monogenic disorders. This panel method ofscreening can benefit high-risk Vietnamese pregnancies, butfurther research is encouraged to expand on the causative gene panel.

Unraveling the Complexity of Apert Syndrome: Genetics, Clinical Insights, and Future Frontiers.

Apert syndrome (AS), also known as type I acrocephalosyndactyly, is a rare congenital condition characterized by craniosynostosis resulting from missense mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. This comprehensive review delves into AS, covering its clinical manifestations, genetics, diagnosis, medical management, psychosocial considerations, and future research directions. AS presents with distinct features, including a brachycephalic skull, midface hypoplasia, and limb anomalies such as syndactyly. It follows an autosomal dominantinheritance pattern with mutations in the FGFR2 gene. Prenatal diagnosis is possible through advanced imaging techniques and molecular testing. The multidisciplinary approach to AS management involves surgical interventions, orthodontics, and psychological support. Although no curative treatment exists, early interventions can significantly improve function and aesthetics. The quality of life for AS patients is influenced by psychosocial factors, necessitating comprehensive support for both patients and their families. Future research directions include gene therapy, understanding cellular responses to FGFR2 mutations, and addressing genetic heterogeneity. Collaborative efforts are vital to advancing knowledge about AS and its genetic underpinnings. Overall, this review serves as a valuable resource for healthcare professionals, educators, and researchers, contributing to a deeper understanding of AS and facilitating advancements in diagnosis and treatment.

Genetic Subtypes of Apert Syndrome Are Associated with Differences in Airway Morphology and Early Upper Airway Obstruction

Genetic Subtypes of Apert Syndrome Are Associated with Differences in Airway Morphology and Early Upper Airway Obstruction

EP06.17: Prenatal diagnosis of Apert syndrome with temporal lobe abnormalities detected on fetal neurosonography

EP06.17: Prenatal diagnosis of Apert syndrome with temporal lobe abnormalities detected on fetal neurosonography

Sensitivity, Specificity, and Cutoff Identifying Optic Atrophy by Macular Ganglion Cell Layer Volume in Syndromic Craniosynostosis

PurposeDetermine sensitivity, specificity, and cut-off of macular ganglion cell layer (GCL) volume consistent with optic atrophy in children with syndromic craniosynostosis (CS). Investigate whether obstructive sleep apnea (OSA), Chiari malformation, history of elevated intracranial pressure (ICP), CS diagnosis, age, or sex independently alter GCL volume with CS. DesignRetrospective cross-sectional study. SubjectsPatients with syndromic CS evaluated at Boston Children’s Hospital (2010 – 2022) with reliable macular optical coherence tomography (OCT) scans. MethodsLatest ophthalmic examination that included OCT macula scans was identified. Age at examination, sex, ethnicity, best-corrected logMAR visual acuity, cycloplegic refraction, and funduscopic optic nerve appearance were recorded in addition to history of primary or recurrent elevated ICP, Chiari malformation and OSA. Spectral domain-OCT software quantified segmentation of macula retinal layers, and was manually checked. Main Outcome MeasuresPrimary outcome was determining sensitivity, specificity and optimal cutoff of GCL volume consistent with optic atrophy. Secondary outcome was determining possible independent association of previously elevated ICP, OSA, Chiari, CS diagnosis, logMAR acuity, age, or sex with altered GCL volume. ResultsMedian age at examination was 11.9 years (interquartile range (IQR), 8.5-14.8 years). Fifty-eight of 61 patients had reliable macula scans, 74% were female, and diagnoses were Apert (n=14); Crouzon (n=17); Muenke (n=6); Pfeiffer (n= 6); and Saethre-Chotzen (n=15). Optimal cutoff identifying optic atrophy was GCL volume <1.02mm3 with a sensitivity of 83% and specificity of 77%. Univariate analysis demonstrated significantly lower macular GCL volume with optic atrophy on fundus exam (P<0.001), Apert syndrome (P<0.001), history of elevated ICP (P=0.015), Chiari malformation (P=0.001), OSA (P<0.001), in males (P=0.027) and with worse logMAR acuity (-0.36, P<0.001). Multivariable median regression analysis confirmed that only OSA (P=0.005), optic atrophy on fundus exam (P=0.003), and worse logMAR acuity (P=0.042) independently associated with lower GCL volume. ConclusionsMacular GCL volume <1.02mm3 predicted optic atrophy in patients with CS with sensitive of 83% and specificity of 77%. OSA, a treatable often concomitant disorder, was independently associated with lower GCL volume. Surveillance for optic neuropathy by GCL volume proved effective in a population where cognitive skills can limit acquisition of other key ophthalmic measures.

Apert syndrome in a Sri Lankan boy with normal head growth and without clinical features of raised intracranial pressure during infancy

No abstract available

Clinical case: radiological

Craniosynostosis is a congenital defect of unknown cause in which one or more sutures of the baby's head close partially or totally earlier than normal, it has an incidence of 1 in 1,000 to 3,000 live births, with higher prevalence in males. The evolution of this disease is different in each case and can be mild or severe. They present symptoms such as: irritability or inconsolable crying and very little activity. As your skull grows, it can become more and more deformed and give different neurological symptoms. It may be due to certain genetic syndromes such as Apert, Pfieffer or Croizon syndrome affecting the development of the baby's skull. We present a case of a newborn with this rare pathology.

Facial Fat Graft Injection Reduces Asymmetry and Improves Forehead Contour in Early Infancy Apert Syndrome Patients.

The objective of this study is to report the outcomes of a modified comprehensive Apert syndrome surgical protocol in which fat injection was performed during early infancy concurrent with postposterior vault distraction osteogenesis (PVDO) distractor removal. A retrospective study was performed on 40 consecutive young patients with Apert syndrome who underwent PVDO and subsequent distractor removal between 2012 and 2022. Of these 40 patients, 12 patients underwent facial fat injection concurrent with distractor removal to treat residual supraorbital bar recession as part of a modified comprehensive Apert syndrome surgical protocol. Preoperative and postoperative severity of recession and irregularity was graded from 1 to 3, with 1 being less severe and 3 being the most severe. Recession severity was correlated with the number and type of suture fusion. The complication rate was stratified via a Clavien-Dindo scale. The average patient age was 14.3±5 months, with 5 males (41.6%) and 7 females (48.3%). The average hospital stay was 1.08 days. The average volume of free fat graft injection was 8.29±5mL. According to the Likert scale, forehead morphology improved in 91.67% of the patients. Complete resolution of supraorbital bar recession was achieved in seven patients (58.33%), all of whom presenting a single suture synostosis. One patient with a cloverleaf skull presented a type IIIB complication. Facial fat grafting markedly reduces forehead asymmetry and improves forehead contour in Apert syndrome patients following PVDO. Total resolution of forehead recession directly correlated with a single suture fusion.

Genetic Subtypes of Apert Syndrome Are Associated With Differences in Airway Morphology and Early Upper Airway Obstruction.

Apert syndrome is predominantly caused by 2 paternally inherited gain-of-function mutations in the FGFR2 gene, Pro253Arg, and Ser252Trp. Studies comparing phenotypic features between these 2 mutations have established differences in syndactyly severity and incidence of cleft palate. Obstructive sleep apnea can be debilitating in a subset of patients with Apert syndrome, yet is not well understood. This study aims to determine whether FGFR2 mutations impart differential effects on airway physiology and morphology. Patients with Apert syndrome and confirmatory molecular testing were reviewed for polysomnography, nasal endoscopy, microlaryngoscopy and bronchoscopy, and computed tomography imaging. Obstructive apnea-hypopnea index and oxygen saturation nadir, nasal airway volumes, choanal cross-sectional area, and midfacial cephalometric dimensions were compared across mutation types. Twenty-four patients (13 Ser252Trp, 11 Pro253Arg) were included. Severe obstructive sleep apnea (obstructive apnea-hypopnea index>10) occurred in 8 (62%) patients with Ser252Trp mutations compared with 1 (9%) patient with Pro253Arg mutations ( P =0.009). Computed tomography imaging at 1 year of age demonstrated that nasopharyngeal airway volumes were 5302±1076mm 3 in the Ser252Trp group and 6832±1414mm 3 in the Pro253Arg group ( P =0.041). Maxillary length (anterior nasal spine-posterior nasal spine, P =0.026) and basion-anterior nasal spine ( P =0.007) were shorter in patients with Ser252Trp mutations. The findings suggest that the Ser252Trp mutation in Apert syndrome is associated with higher severity obstructive sleep apnea and decreased nasopharyngeal airway volume. Heightened clinical awareness of these associations may inform treatment planning and family counseling.

Outcomes of Apert Syndrome Hand Reconstruction With Tilapia Skin: A Prospective Study.

Tilapia skin has already been used in various medical scenarios, but there are no studies showing the use of tilapia skin for hand reconstruction in Apert syndrome. The objective of this study is to determine whether the use of tilapia skin during graft bed preparation for children with Apert syndrome can shorten wound reepithelialization intervals, reduce the number of dressing changes, and decrease patient discomfort. This is a prospective study on consecutive patients with Apert syndrome who underwent hand reconstruction at our Hospital. Patients were divided into 2 groups: (1) a control group consisting of patients who underwent conventional digit separation hand reconstruction surgery (2) an experimental group consisting of patients who underwent similar digit separation hand reconstruction surgery that commenced with the placement of a thin layer of tilapia skin at the raw commissures during a first operation, which was subsequently replaced by an autologous skin graft during a second operation staged 10 days postoperatively. Pain assessment was performed using the Visual Analog Scale. The number of dressing changes was also assessed. A T test compared the total number of dressings changes and pain data. Experimental group patients (n = 8) required an average of 9.4 days of daily dressing changes, and control group patients (n = 5) required an average of 20.8 days of daily dressing changes ( P < 0.05) and tended to experience significantly less pain when compared with patients in the control group ( P = 0.079). Tilapia skin can shorten wound reepithelialization intervals by reducing the total number of dressing changes.

Male reproductive ageing: a radical road to ruin.

In modern post-transition societies, we are reproducing later and living longer. While the impact of age on female reproductive function has been well studied, much less is known about the intersection of age and male reproduction. Our current understanding is that advancing age brings forth a progressive decline in male fertility accompanied by a reduction in circulating testosterone levels and the appearance of age-dependent reproductive pathologies including benign prostatic hypertrophy and erectile dysfunction. Paternal ageing is also associated with a profound increase in sperm DNA damage, the appearance of multiple epigenetic changes in the germ line and an elevated mutational load in the offspring. The net result of such changes is an increase in the disease burden carried by the progeny of ageing males, including dominant genetic diseases such as Apert syndrome and achondroplasia, as well as neuropsychiatric conditions including autism and spontaneous schizophrenia. The genetic basis of these age-related effects appears to involve two fundamental mechanisms. The first is a positive selection mechanism whereby stem cells containing mutations in a mitogen-activated protein kinase pathway gain a selective advantage over their non-mutant counterparts and exhibit significant clonal expansion with the passage of time. The second is dependent on an age-dependent increase in oxidative stress which impairs the steroidogenic capacity of the Leydig cells, disrupts the ability of Sertoli cells to support the normal differentiation of germ cells, and disrupts the functional and genetic integrity of spermatozoa. Given the central importance of oxidative stress in defining the impact of chronological age on male reproduction, there may be a role for antioxidants in the clinical management of this process. While animal studies are supportive of this strategy, carefully designed clinical trials are now needed if we are to realize the therapeutic potential of this approach in a clinical context.

Cleft Palate in Apert Syndrome: A Descriptive Study of Incidence and Surgical Outcome.

Apert syndrome (AS) is a rare congenital craniofacial disorder that requires a multidisciplinary approach to treatment and multiple surgeries. Given that cleft palate (CP) is presented in some of these cases, this poses an additional risk of aggravating obstructed airways after closure. The timing and outcome of CP repair in these patients remains disputed and requires additional attention. This retrospective analysis included patients diagnosed with CP and AS, born between 1950 and 2020, and treated at our institution. Data were collected from medical records and evaluated using descriptive statistics. Data analyses were conducted at Sahlgrenska University Hospital in Gothenburg, Sweden. A registry of 83 patients with AS resulted in a cohort of 26 patients also presenting with CP. Postoperative complications, requirement for intensive care, and reoperations following CP repair. CP incidence among all registered patients was 31%. Patients undergoing CP repair at low age (mean: 22.5 months) tended to experience more frequent postoperative complications and requirements for intensive care. Among the evaluated cohort with medical records describing CP repair (n = 14), 29% experienced postoperative complications, all of which involved aggravation of obstructed airways. This study highlights the importance of airway assessment before and after CP repair in AS. The findings suggest that surgical outcomes might benefit from postponing CP repair, avoiding combined surgeries, and operating in two stages when indicated. However, additional and larger studies are required.

Anesthesia for preoperative non-invasive intracranial pressure measurement in a child with Apert syndrome: a case report

Introduction: The presence of craniofacial alterations such as craniosynostosis and midface hypoplasia are some features of Apert syndrome. Those characteristics may lead to intracranial hypertension. For clinical evaluation, a non-invasive intracranial pressure measurement can be performed both as a preoperative examination and to evaluate surgical treatment. Several methods have been used to measure intracranial pressure non-invasively, such as optic nerve sheath ultrasound, optical coherence tomography, and intracranial pressure waveform (ICPw) monitoring with the sensor Brain4Care®. Some methods like ICPw, require that the patient remains standstill. Because the patient wasn’t cooperative, it was decided to register the ICPw under hypnosis. A specific anesthetic planning was done to minimize the impact on the ICPw. Case presentation: We present a 6 years old child with Apert Syndrome with ICPw registered by Brain4Care® device before and after monobloc craniofacial advancement with internal distraction. The chosen anesthetic was Sevoflurane at a dose ≤ 0.9% of inspired gases and air/oxygen proportion of 50/50%, with a laryngeal mask, under spontaneous ventilation, with normal end-tidal CO2 range. The preoperative ICPw suggested low cranial compliance, with a mean P2/P1 index above 1,2. The postoperative showed a mean P2/P1 index under 1.2, demonstrating improved cranial compliance. The same anesthetic planning was done on both occasions. Conclusion: Likely, an appropriate way to obtain a reliable non-invasive ICPw measurement under hypnosis includes positioning the patient at neutral decubitus, choosing hypnotics with minimal impact on ICP, and maintaining spontaneous ventilation during the exam.

WITHDRAWN: Two-stage surgical treatment for medially angulated great toes in Apert feet by wedged corrective osteotomy with distraction of the inter-metatarsal space: A case report

One of most severe clinical problems related to Apert foot anomalies is medial angulation deformities of the great toe as the foot grows. The patient was a 22-month-old Japanese child with Apert syndrome, who had broad bilateral great toe showing medially angulated deformity. We performed two-stage surgical treatment including distraction of the remarkable narrowing the first inter-metatarsal space using an external distractor device, and the corrective wedge-osteotomy of the first metatarsal with a graft of wedged bone in the reverse direction and inter-positioning of the resected local bone between the first and second metatarsal to preserve the space. At 3 years after surgery, the patient did not have any disturbance of gait and could wear normal shoes without weight-bearing pain, and was satisfied with the appearance of the great toes. The two-stage surgical method could be an option for surgical treatment of Apert feet.

APERT SYNDROME : A CASE REPORT

Apert syndrome (AS) is indeed a rare congenital disorder that falls under the category of acrocephalosyndactyly. It is characterized by several distinct features, including craniosynostosis (premature fusion of certain skull bones), midface hypoplasia (underdevelopment of the middle part of the face), and syndactyly (fusion) of the hands and feet.The syndrome is typically caused by mutations in the fibroblast growth factor receptor gene (FGFR2). These mutations are inherited in an autosomal dominant pattern, which means that an affected individual has a 50% chance of passing the syndrome on to their children.Diagnosing Apert syndrome can be challenging due to its rarity and similarities with other craniosynostosis syndromes. However, certain key features can help differentiate it from other conditions. These features include early fusion of the coronal suture , cranial base synostosis , and agenesis (absence) of the sagittal suture (the suture running along the top of the skull).The characteristic appearance and dental features of Apert syndrome include maxillary transverse and sagittal hypoplasia, dental crowding, a pseudo-cleft palate and skeletal and dental anterior open bite.Given the multiple phenotypic signs and complex nature of the syndrome, successful management of Apert syndrome requires a multidisciplinary team approach. This team typically includes professionals from various specialties such as dentistry, neurosurgery, plastic surgery, psychiatry, ophthalmology, perinatology, and genetics. Each specialist contributes their expertise to provide comprehensive care and support for individuals with Apert syndrome.

A case report of Apert syndrome

Link of Video Abstract: https://youtu.be/ahjJloTwZQE Introduction: Apert syndrome (AS) is a rare type 1 acrocephalosyndactyly syndrome, characterized by craniosynostosis, severe syndactyly of the hands and feet, and dysmorphic facial features. It exhibits autosomal dominant inheritance assigned to mutations in the fibroblast growth factor receptor gene. Case Illustration: We presently describe the case of a 14 years old male patient with acrocephaly, prominent forehead, ocular hypertelorism, proptosis, short and broad nose, pseudoprognathism, crowding of teeth and ectopia, maxillary hypoplasia, low hairline, webbed neck, pectus excavatum, and severe bilateral syndactyly of hands and feet. The examination revealed apical cranium, occipital flattening, enlargement and hypoplasia of the premaxillary opening, crowding, ectopic teeth, tapering of the mandibular apex, and pseudognathia. Conclusion: We reported a 14 years old male patient with AS with craniosynostosis and acrocephalosyndactyly. The characteristics of clinical manifestation of AS should be aware by physicians to be able to diagnose the disease.