Apert Syndrome Research Articles

Introduction of Spring-Assisted Cranioplasty for Bicoronal Synotosis in India: Description of First Case and Our Learning Experience.

Various surgical techniques for cranial reconstruction of patients with bicoronal synostosis have been suggested. The outcome is, however, still often suboptimal. In a 5-month-old child with apert syndrome, following a craniotomy incision, lambdoid suturotomy was done bilaterally. Two springs were implanted bilaterally over the lambdoid sutures. Cephalic index was obtained from three-dimensional computed tomography scans, and photographs were analyzed for aesthetic evaluation. The preoperative calvarial shape was hyperbrachycephalic. The CI improved from 92 to 83 units. Duration of surgery was 1 h 45 min, blood loss was 30 mL, and total hospital stay was 3 days. No major complications were observed. Spring removal was done at 6 months postoperatively and frontoorbital advancement performed. Spring-assisted cranioplasty for bicoronal synostosis is a safe and elegant technique, is less invasive than many other cranioplasties, and results in marked improvement in the calvarial shape.

Evaluation of polysomnography findings in children with genetic skeletal disorders.

Children with genetic skeletal disorders have variable conditions that can lead to sleep-disordered breathing, and polysomnography is the gold standard for diagnosing this condition. We aimed to review polysomnography findings, to assess the severity of sleep apnea, and to investigate the clinical variables predictive of sleep-disordered breathing in these patients. We retrospectively collected the medical records of patients with genetic skeletal disorders who underwent polysomnography for 5 years. Twenty-seven children with various genetic skeletal disorders, including achondroplasia (14), Crouzon syndrome (3), acromesomelic dysplasia Maroteaux type (3), Apert syndrome (2), osteopetrosis (1), Jeune dysplasia (1), Desbuquois dysplasia (1), acrodysostosis (1), and spondyloepiphyseal dysplasia (1) were enrolled. The median age at the first polysomnography was 58 (1st-3rd quartile: 31-113) months. The overall sleep-disordered breathing results were: 19 (70.3%) had obstructive sleep apneas (OSA) (4 mild, 6 moderate, 9 severe), 2 (7.4%) had central apneas, 4 (14.8%) had nocturnal hypoventilation. There was a significant correlation between non-ambulatory status with both total AHI and OSA (p < 0.001, rho: -0.66/p = 0.04, rho: 0.38, respectively). Nine patients received positive airway pressure titration, and the oAHI values of all returned to the normal range. These patients were started with positive airway pressure treatment. Our cohort showed that the majority of the patients with skeletal dysplasia had sleep apnea syndrome characterised mainly by OSA, highlighting the importance of polysomnography screening for sleep disorders. Positive airway pressure therapy represents an effective treatment for sleep-disordered breathing in those patients.

Abstract IA18: Somatic predisposition to germline mutations in the RTK/RAS/MAPK pathway

Abstract Somatic and germline mutations are traditionally viewed as separate entities. Yet, it is well established that germline variants (either inherited or occurring spontaneously) can influence cancer risk - i.e. cancer predisposition syndromes. In this presentation, I will discuss the reverse (but complementary) concept and propose that de novo germline mutations in the RTK/RAS/MAPK pathway occur recurrently because they confer a selective advantage to testicular stem cells, leading to the formation of ‘mole-like’ mutant clones in the ageing testis. This universal mechanism called ‘selfish selection’ relies on principles akin to oncogenesis and explains the paternal age-effect and high birth prevalence observed for several Mendelian disorders, including Noonan (PTPN11), Costello (HRAS), Apert (FGFR2) syndromes and achondroplasia (FGFR3). I will describe the strategies we have developed to show that the human testis is a repository of pathogenic de novo mutations and that selfish ‘moles’ are prevalent in older men’s testes. Our data show that the male germline is particularly vulnerable to dysregulation of the RTK/RAS/MAPK pathway. Importantly, because the germline provides a source of heritable material (unlike somatic tissues), this phenomenon has implications that extend far beyond the individual in whom it takes place, and is predicted to affect disease prevalence, genome heterogeneity and evolution of our species. This process illustrates another facet of the fascinating biology of the RAS/MAPK pathway. Citation Format: Anne Goriely. Somatic predisposition to germline mutations in the RTK/RAS/MAPK pathway [abstract]. In: Proceedings of the AACR Special Conference: Targeting RAS; 2023 Mar 5-8; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Res 2023;21(5_Suppl):Abstract nr IA18.

Molecular Scalpels: The Future of Pediatric Craniofacial Surgery?

CRISPR-Cas genome editing tools are among the most substantial advances in the life sciences in modern history. Single-dose gene therapies to correct pathogenic mutations have moved quickly from bench to bedside, with several therapeutics designed by CRISPR pioneers entering various stages of clinical investigation. Applications of these genetic technologies are poised to reshape the practice of both medicine and surgery. Many of the most morbid conditions treated by craniofacial surgeons are syndromic craniosynostoses caused by mutations in fibroblast growth factor receptor genes, including Apert, Pfeiffer, Crouzon, and Muenke syndromes. The fact that pathogenic mutations in these genes are recurrent in the majority of affected families presents a unique opportunity to develop "off-the-shelf" gene editing therapies to correct these mutations in affected children. The therapeutic potential of these interventions could reshape pediatric craniofacial surgery, potentially first eliminating the need for midface advancement procedures in affected children.

Spectrum of ocular manifestations in apert syndrome

Apert syndrome is a congenital type 1 acrocephalosyndactyly characterized by craniosynostosis, dysmorphic facial features and symmetrical syndactyly. There is premature fusion of cranial sutures which leads to restriction of intracranial and orbital space expansion giving characteristic dysmorphic facial appearance. We are reporting two cases of Apert syndrome of different age groups from ophthalmic point of view, and with different sets of ocular manifestation. Of the two cases, the one who presented early had a better visual prognosis. Apert Syndrome has a social stigma and the patients often suffers social and psychological disturbances. Patient counselling, timely management by multidisciplinary approach and regular follow ups are an important aspect which can offer a better quality of life.

Meticulous morphological assessment and correlation with genomics in diagnosing a rare genetic syndrome in the second trimester: a case report of Apert syndrome

Whilst modern imaging modalities have far advanced antenatal diagnoses, the perinatal autopsy remains the gold standard in confirming and assessing fetal dysmorphology. The presence of multiple abnormalities involving several organ systems raises clinical suspicion of an underlying genetic syndrome.

Discussion of "Does the Mutation Type Affect the Response to Cranial Vault Expansion in Children With Apert Syndrome?"

Raposo-Amaral, Cassio Eduardo MD, PhD*,†; Raposo-Amaral, Cesar Augusto MD*; Ghizoni, Enrico MD, PhD*,† Author Information

Three-Dimensional Evaluation of Dental Arches in Individuals with Syndromic Craniosynostosis.

Individuals with syndromic craniosynostosis present alterations in the dental arches due to anomalies caused by the early fusion of the craniomaxillary sutures. This study aimed to compare intradental and interdental dimensions between individuals with Apert and Crouzon syndromes and nonsyndromic controls. Digital models were obtained from the archive of a public tertiary care hospital. The sample consisted of 34 patients (Apert n = 18, Crouzon n = 16) and 34 nonsyndromic controls matched for gender and age. Measurements of perimeter, length, intercanine and intermolar distances (upper and lower), overjet, and molar ratio were performed. Statistical comparisons were performed using ANOVA and Tukey tests (p < 0.05). Patients with Apert and Crouzon syndromes have severely reduced maxillary transverse dimensions, perimeter, and length of the upper arch compared to the control group (p < 0.001). The lower arch is less impacted. Patients with Apert syndrome had an anterior crossbite (p < 0.001), while patients with Crouzon syndrome had an edge-to-edge bite (p < 0.011). Patients with Apert and Crouzon syndromes do not have serious transverse proportion problems when comparing the upper and lower arches. In this sample, both the Apert and Crouzon groups have severely compromised upper arches compared to the control group. Mild dentoalveolar expansion in the maxilla should be sufficient for the transverse adaptation of the dental arches before frontofacial advancement.

Apert Syndrome: Selection Rationale for Midface Advancement Technique.

Apert syndrome is characterized by a wide spectrum of craniofacial clinical features that have been successfully addressed via a variety of midface advancement techniques. Although surgeons have individual preferences as to which specific procedures should be performed to best treat Apert patients, craniofacial plastic surgeons, working in tandem with pediatric neurosurgeons, can identify and evaluate functional limitations and facial morphologic disproportions, and establish appropriate criteria for effective midface advancement technique indication and selection. The purpose of this review article is to present and discuss our rationale for midface advancement technique selection based upon the most common craniofacial characteristics presented by Apert syndrome patients. The present article also provides a grading system that stratifies as major, moderate, and mild, the effect of each midface advancement technique on the different types of Apert syndrome facial features. Surgeons should take into consideration the maximum effect and benefit of each craniofacial osteotomy and how these procedures will alter the craniofacial skeleton. By understanding the long-term effect of each osteotomy on the most common craniofacial characteristics of Apert syndrome patients, craniofacial plastic surgeons and neurosurgeons will be able to customize the surgical procedures they perform in order to achieve the best possible outcomes.

Anaesthetic challenges in apert syndrome : A case series.

Apert syndrome is an autosomal dominant inherited condition characterised by craniosynostosis, syndactyly, mid face hypoplasia, organ malformations, and mental retardation. As it is rarely encountered, so there is little knowledge of the anaesthesia practice in the literature for this syndrome, we present our experience of two cases undergoing bilateral syndactyly release under general anaesthesia.

Orofacial Manifestations in Apert Syndrome: A Case Report and a Review of the Literature

Orofacial Manifestations in Apert Syndrome: A Case Report and a Review of the Literature

Apert syndrome: a rare clinical image.

Apert syndrome: a rare clinical image.

Molecular Mechanisms Involved in Craniosynostosis.

Craniosynostosis refers to the early fusion of one or many cranial sutures, causing craniofacial abnormalities observed in 1:2,500 births worldwide. In most cases (85%), craniosynostosis is presented as sporadic anomaly (non-syndromic craniosynostosis), while in other cases (15%) as part of syndromes (syndromic craniosynostosis). Patients with syndromic disorder usually have more severe symptoms compared to those with single suture synostosis. Most common syndromes of craniosynostosis include Pfeiffer, Apert, Crouzon, Jackson-Weiss, Muenke and Boston type MSX2-related syndrome. The main gene mutations in craniosynostosis involve FGFR1, FGFR2, FGFR3, TWIST1 and MSX2, which encode key factors influencing cranial bone morphogenesis. The main therapeutic approaches are surgical as discussed in this review, and the type of therapy depends on the graveness of the incident.

Apert Syndrome

Apert Syndrome is a rare genetic disorder that presents with craniosynostosis, syndactyly and midface retrusion with dysostosis as well as many other anomalies. Apert Syndrome is an autosomal dominant syndrome that presents equally in males and females and has an occurrence rate of 1 in every 65,000.

Fetal Hand Anomalies: 18 Cases Diagnosed Between 2020-2022 from a Single Tertiary Care Center

Objective: The aim of this study was to present and investigate fetal cases with hand anomalies by discussing their antenatal and postmortem findings. Materials and Methods: This retrospective review re-evaluates fetal cases identified antenatally with hand anomalies including polydactyly, syndactyly, reduction defects, and oligodactyly. The following data were collected from the patients’ medical records: Demographic information, family histories, X-ray images, photographs, and cytogenetic/molecular findings. The study also performed a chromosome analysis, array-comparative genomic hybridization (CGH), and Sanger sequencing of FGFR2 and GLI3 genes. Results: This study involved 18 cases with hand anomalies, all of which were diagnosed antenatally. Three cases were diagnosed with Greig cephalopolysyndactyly, Apert Syndrome, and triploidy, respectively. Conclusions: Fetal ultrasonography is the most valuable tool for providing prenatal diagnosis. Prenatal detection of hand anomalies causes great anxiety for parents; therefore, making an accurate diagnosis list is important for the prenatal period. Prenatal diagnosis and management of hand anomalies must involve a multidisciplinary team composed of a perinatologist, a clinical geneticist, and a hand surgeon.

Apert Syndrome: Radiologist’s Perspective

Background: Apert syndrome (acrocephalosyndactyly type 1) is a rare syndrome, well known by severe syndactyly, dysmorphic face and craniosynostosis and is caused by FGF (fibroblast growth factor) receptor-2 gene mutations. Case Report: This is a case report of one year old girl child who presented with syndactyly of bilateral hands and feet, delayed milestones and dysmorphic facial features. Radiograph of the hands and feet of the patient revealed bilateral soft tissue and bony syndactyly, single broadened dysplastic phalanx in both great toes and presence of only two phalanges in 2nd to 5th toes. Non-contrast computed tomography of the head revealed bi-coronal synostosis and a widely open midline calvarial defect extending from posterior fontanelle to the root of the nose with hypoplastic bilateral maxillae. Intra-parenchymal findings including ventriculomegaly, corpus callosum thinning, absent cavum septum pellucidum and enlarged cystic space in posterior fossa were also present. Conclusion: Recognition of characteristic clinical and imaging abnormalities are crucial to radiologists and clinicians in the diagnosis and management of these patients. Since there is multi-system involvement, a multidisciplinary approach is needed in the management of patients.

Apert Syndrome: A Case Report

Background : Apert syndrome is a rare autosomal dominant disorder characterized by craniosynostosis, facial dysmorphism and syndactyly of hands and feet. Eugene Apert in 1906 describe the syndrome acrocephalosyndactyly.&#x0D; Case Presentation : The reporting case was a 3 months old female baby presented with early fusion of all cranial bone, facial dimorphism like hypertelorism, cleft palate and syndactyly of both hands and feet. There was some bony defect also found in radioligy.&#x0D; Conclusion : It is a noncurable disease but treat with multidisciplinary approach can reduce the complication and prevention can be done by genetic counselling and antenatal ultrasonography.&#x0D; Chatt Maa Shi Hosp Med Coll J; Vol.21 (2); July 2022; Page 60-63

Isografting of full-thickness skin to treat syndactyly in monozygotic twins with Apert syndrome: a case report

Patients with Apert syndrome require repeated limb surgery due to their complex deformities. In this study, a full-thickness isograft was performed for the division of Upton type III hands in identical twins with Apert syndrome. Nine-month-old identical twins presented with Apert syndrome characterized by craniosynostosis, severe syndactyly of the hands and feet, and dysmorphic facial features. Division and full-thickness skin grafting were performed. The siblings were operated consecutively on the same day. Following surgery for the younger sibling, there was an excess of graft left unused. In contrast, the older sibling required an additional skin graft of 1 × 1 cm. Full-thickness skin was successfully transferred between the twins without any rejection as of a 2-month follow-up. Thus, full-thickness skin isografting between monozygotic twins with Apert syndrome was successfully implemented.

Apert Syndrome with Agenesis of the Corpus Collosum - Case Report

Abstract Apert syndrome (Acrocephalosyndactylia type 1) belongs to the group of extremely rare congenital dysmorphic syndromes. It is characterized by craniostenosis with very early fusion of the skull and / or cranial base sutures, facial hypoplasia, symmetrical syndactyly of the fingers and toes and other systemic malformations. Multiple CNS abnormalities are common, but simultaneous occurrence of Apert syndrome and agenesis of corpus callosum is estimated about 10%. We present a male patient born after first, normal and controlled pregnancy and term, naturally birth, in which the Apert syndrome was diagnosed, based on the clinical presentation of the skull and face and syndactyly of fingers and toes. Neurological examination established generalized hypotonia and aggravated provocation of the primitive reflexes. Neurosonography showed complete agenesis of the corpus callosum, which makes this case a rare form of this syndrome. The head X-rays showed turricephalic skull shape and suture’s synostoses, which is demonstrated in more detail at computed tomography finding. The hands and feet X-rays showed bone synostosis of fingers and toes. The video-electroencephalogram recorded intermittent depression of electrocortical activity. There was conducted the multidisciplinary examination in order to examine the possibility of reconstructive and plastic surgical correction of the anomalies. The neurodevelopmental disorders in patients with Apert syndrome can be manifested by a variety of congenital malformations, but considering its rare occurrence, the significance of these abnormalities remains unknown.

Does the Mutation Type Affect the Response to Cranial Vault Expansion in Children With Apert Syndrome?

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