-
Cureus Dec 2023Craniosynostosis is a fetal skull condition that occurs when one or multiple sutures merge prematurely. This leads to limited growth perpendicular to the fused suture,... (Review)
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.
PubMed: 38222144
DOI: 10.7759/cureus.50448 -
Cureus Oct 2023Apert syndrome (AS), also known as type I acrocephalosyndactyly, is a rare congenital condition characterized by craniosynostosis resulting from missense mutations in... (Review)
Review
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 () 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 dominant inheritance pattern with mutations in the 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 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.
PubMed: 38021759
DOI: 10.7759/cureus.47281 -
Facial Plastic Surgery Clinics of North... Feb 2024This article reviews the most common craniofacial syndromes encountered in clinical practice. Key physical features of each condition are highlighted to aid in accurate... (Review)
Review
This article reviews the most common craniofacial syndromes encountered in clinical practice. Key physical features of each condition are highlighted to aid in accurate recognition and diagnosis. Optimal individualized treatment approaches are discussed.
Topics: Humans; Physical Examination; Syndrome
PubMed: 37981410
DOI: 10.1016/j.fsc.2023.07.002 -
Human Reproduction (Oxford, England) Oct 2023In 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...
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.
Topics: Animals; Male; Female; Semen; Reproduction; Aging; Spermatozoa; Mutation
PubMed: 37568254
DOI: 10.1093/humrep/dead157 -
The Cleft Palate-craniofacial Journal :... Aug 2023Apert syndrome (AS) is a rare congenital craniofacial disorder that requires a multidisciplinary approach to treatment and multiple surgeries. Given that cleft palate...
OBJECTIVE
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.
DESIGN
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.
SETTING
Data analyses were conducted at Sahlgrenska University Hospital in Gothenburg, Sweden.
PATIENTS/PARTICIPANTS
A registry of 83 patients with AS resulted in a cohort of 26 patients also presenting with CP.
MAIN OUTCOME MEASURES
Postoperative complications, requirement for intensive care, and reoperations following CP repair.
RESULTS
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 (= 14), 29% experienced postoperative complications, all of which involved aggravation of obstructed airways.
CONCLUSIONS
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.
PubMed: 37563888
DOI: 10.1177/10556656231194445 -
Child's Nervous System : ChNS :... May 2024Posterior vault distraction osteogenesis (PVDO) has been utilized during the past 15 years to treat a variety of clinical features commonly presented by patients with...
PURPOSE
Posterior vault distraction osteogenesis (PVDO) has been utilized during the past 15 years to treat a variety of clinical features commonly presented by patients with Apert syndrome. The objective of this study is to determine the efficacy of PVDO in addressing both elevated intracranial pressure (ICP) and ectopia of the cerebellar tonsils (ECT) in young Apert patients. In addition, we aimed to determine the prevalence of hydrocephalus in Apert syndrome patients who underwent PVDO.
METHODS
A retrospective study was made with a cohort of 40 consecutive patients with syndromic craniosynostosis (SC), previously diagnosed with Apert syndrome, who underwent PVDO between 2012 and 2022, and thereafter received at least 1 year of follow-up care. Demographic data and diagnosis, along with surgical and outcome data, were verified using medical records, clinical photographs, radiologic examination, and interviews with the parents of all cohort patients.
RESULTS
The average patient age when PVDO was performed was 12.91 ± 10 months. The average posterior advancement distance achieved per patient was 22.68 ± 5.26 mm. The average hospital stay per patient was 3.56 ± 2.44 days. The average absolute and relative blood transfusion volumes were 98.47 ml and 17.63 ml/kg, respectively. Although five patients (14%) presented ECT preoperatively, this condition was completely resolved by PVDO in three of these five patients. One of the three patients whose ECT had completely resolved presented syringomyelia postoperatively, requiring subsequent extra dural foramen magnum decompression. All of the remaining four patients were asymptomatic for ECT for at least 1 year of follow-up, and none of these four patients required any additional treatments to address ECT. Two patients presented hydrocephalus requiring ventriculoperitoneal shunt placement.
CONCLUSIONS
This study demonstrates that PVDO both reduces diagnosed elevated ICP symptoms and is partially effective in treating ECT in Apert syndrome patients. Hydrocephalus in Apert syndrome is an uncommon feature. The effectiveness of PVDO in addressing hydrocephalus is uncertain.
PubMed: 38700706
DOI: 10.1007/s00381-024-06436-2 -
The Journal of Craniofacial Surgery Oct 2023Apert syndrome is predominantly caused by 2 paternally inherited gain-of-function mutations in the FGFR2 gene, Pro253Arg, and Ser252Trp. Studies comparing phenotypic...
BACKGROUND
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.
METHODS
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.
RESULTS
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±1076 mm 3 in the Ser252Trp group and 6832±1414 mm 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.
CONCLUSIONS
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.
PubMed: 37582295
DOI: 10.1097/SCS.0000000000009583