-
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 -
Nature Communications May 2018Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association... (Meta-Analysis)
Meta-Analysis
Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = -0.62, P = 5.30 × 10) but not between CCT and primary open-angle glaucoma (r = -0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.
Topics: ADAMTS Proteins; Asian People; Cornea; Corneal Diseases; Corneal Dystrophies, Hereditary; Decorin; Ehlers-Danlos Syndrome; Eye Diseases, Hereditary; Fibrillin-1; Gene Expression; Genome, Human; Genome-Wide Association Study; Glaucoma, Open-Angle; Humans; Keratoconus; Loeys-Dietz Syndrome; Lumican; Marfan Syndrome; Mendelian Randomization Analysis; Myopia; Polymorphism, Single Nucleotide; Proteoglycans; Quantitative Trait Loci; Quantitative Trait, Heritable; Transforming Growth Factor beta2; White People
PubMed: 29760442
DOI: 10.1038/s41467-018-03646-6 -
Journal of Anaesthesiology, Clinical... Jul 2011
PubMed: 21897525
DOI: 10.4103/0970-9185.83699 -
Revue Medicale de Liege Oct 2021Apert syndrome, or acrocephalosyndactilia type I, is a rare genetic disorder caused by mutations in the FGFR2 gene and characterized by craniosynostosis, craniofacial...
Apert syndrome, or acrocephalosyndactilia type I, is a rare genetic disorder caused by mutations in the FGFR2 gene and characterized by craniosynostosis, craniofacial dysmorphia and symmetrical syndactyly of the hands and feet. The estimated prevalence of this syndrome is 10 to 15.5 cases per 1,000,000 live births. This syndrome presents significant clinical variability and its early diagnosis is essential. We report an isolated case of Apert syndrome, diagnosed during follow-up of a biamniotic bichorium twin pregnancy.
Topics: Acrocephalosyndactylia; Craniosynostoses; Female; Humans; Mutation; Pregnancy; Receptor, Fibroblast Growth Factor, Type 2; Syndactyly
PubMed: 34632738
DOI: No ID Found -
International Journal of Biological... 2017Craniosynostosis results from the premature fusion of cranial sutures, with an incidence of 1 in 2,100-2,500 live births. The majority of cases are non-syndromic and... (Review)
Review
Craniosynostosis results from the premature fusion of cranial sutures, with an incidence of 1 in 2,100-2,500 live births. The majority of cases are non-syndromic and involve single suture fusion, whereas syndromic cases often involve complex multiple suture fusion. The fibroblast growth factor receptor 2 () gene is perhaps the most extensively studied gene that is mutated in various craniosynostotic syndromes including Crouzon, Apert, Pfeiffer, Antley-Bixler, Beare-Stevenson cutis gyrata, Jackson-Weiss, Bent Bone Dysplasia, and Seathre-Chotzen-like syndromes. The majority of these mutations are missense mutations that result in constitutive activation of the receptor and downstream molecular pathways. Treatment involves a multidisciplinary approach with ultimate surgical fixation of the cranial deformity to prevent further sequelae. Understanding the molecular mechanisms has allowed for the investigation of different therapeutic agents that can potentially be used to prevent the disorders. Further research efforts are need to better understand screening and effective methods of early intervention and prevention. Herein, the authors provide a comprehensive update on related syndromic craniosynostosis.
Topics: Craniosynostoses; Humans; Receptor, Fibroblast Growth Factor, Type 2; Signal Transduction; Syndrome
PubMed: 29230096
DOI: 10.7150/ijbs.22373 -
Plastic and Reconstructive Surgery.... Oct 2020Episodes of intracranial hypertension are associated with reductions in cerebral cortical thickness (CT) in syndromic craniosynostosis. Here we focus on Crouzon-Pfeiffer...
BACKGROUND
Episodes of intracranial hypertension are associated with reductions in cerebral cortical thickness (CT) in syndromic craniosynostosis. Here we focus on Crouzon-Pfeiffer syndrome patients to measure CT and evaluate associations with type of primary cranial vault expansion and synostosis pattern.
METHODS
Records from 34 Crouzon-Pfeiffer patients were reviewed along with MRI data on CT and intracranial volume to examine associations. Patients were grouped according to initial cranial vault expansion (frontal/occipital). Data were analyzed by multiple linear regression controlled for age and brain volume to determine an association between global/lobar CT and vault expansion type. Synostosis pattern effect sizes on global/lobar CT were calculated as secondary outcomes.
RESULTS
Occipital expansion patients demonstrated 0.02 mm thicker cortex globally ( = 0.81) with regional findings, including: thicker cortex in frontal (0.02 mm, = 0.77), parietal (0.06 mm, = 0.44) and occipital (0.04 mm, = 0.54) regions; and thinner cortex in temporal (-0.03 mm, = 0.69), cingulate (-0.04 mm, = 0.785), and, insula (-0.09 mm, = 0.51) regions. Greatest effect sizes were observed between left lambdoid synostosis and the right cingulate (d = -1.00) and right lambdoid synostosis and the left cingulate ( = -1.23). Left and right coronal synostosis yielded effect sizes of = -0.56 and = -0.42 on respective frontal lobes.
CONCLUSIONS
Both frontal and occipital primary cranial vault expansions correlate to similar regional CT in Crouzon-Pfeiffer patients. Lambdoid synostosis appears to be associated with cortical thinning, particularly in the cingulate gyri.
PubMed: 33173703
DOI: 10.1097/GOX.0000000000003204 -
Andrology May 2014Owing to a recent trend for delayed paternity, the genomic integrity of spermatozoa of older men has become a focus of increased interest. Older fathers are at higher... (Review)
Review
Owing to a recent trend for delayed paternity, the genomic integrity of spermatozoa of older men has become a focus of increased interest. Older fathers are at higher risk for their children to be born with several monogenic conditions collectively termed paternal age effect (PAE) disorders, which include achondroplasia, Apert syndrome and Costello syndrome. These disorders are caused by specific mutations originating almost exclusively from the male germline, in genes encoding components of the tyrosine kinase receptor/RAS/MAPK signalling pathway. These particular mutations, occurring randomly during mitotic divisions of spermatogonial stem cells (SSCs), are predicted to confer a selective/growth advantage on the mutant SSC. This selective advantage leads to a clonal expansion of the mutant cells over time, which generates mutant spermatozoa at levels significantly above the background mutation rate. This phenomenon, termed selfish spermatogonial selection, is likely to occur in all men. In rare cases, probably because of additional mutational events, selfish spermatogonial selection may lead to spermatocytic seminoma. The studies that initially predicted the clonal nature of selfish spermatogonial selection were based on DNA analysis, rather than the visualization of mutant clones in intact testes. In a recent study that aimed to identify these clones directly, we stained serial sections of fixed testes for expression of melanoma antigen family A4 (MAGEA4), a marker of spermatogonia. A subset of seminiferous tubules with an appearance and distribution compatible with the predicted mutant clones were identified. In these tubules, termed 'immunopositive tubules', there is an increased density of spermatogonia positive for markers related to selfish selection (FGFR3) and SSC self-renewal (phosphorylated AKT). Here we detail the properties of the immunopositive tubules and how they relate to the predicted mutant clones, as well as discussing the utility of identifying the potential cellular source of PAE mutations.
Topics: Achondroplasia; Acrocephalosyndactylia; Aging; Antigens, Neoplasm; Costello Syndrome; Humans; MAP Kinase Signaling System; Male; Mutation; Neoplasm Proteins; Paternal Age; Proto-Oncogene Proteins c-akt; Receptor, Fibroblast Growth Factor, Type 3; Seminiferous Tubules; Spermatogonia; Spermatozoa; Testis
PubMed: 24357637
DOI: 10.1111/j.2047-2927.2013.00175.x -
Diagnostics (Basel, Switzerland) Nov 2023Abnormal retrobulbar hemodynamics have been linked to the development of various ocular diseases, including glaucoma, age-related macular degeneration, and diabetic... (Review)
Review
Abnormal retrobulbar hemodynamics have been linked to the development of various ocular diseases, including glaucoma, age-related macular degeneration, and diabetic retinopathy. Additionally, altered retrobulbar blood flow has been observed in patients with severe cardiovascular diseases, including carotid artery occlusion, stroke, heart failure, and acute coronary syndrome. Due to the complex and intricate anatomy of retrobulbar blood vessels and their location behind the eyeball, measurement of retrobulbar blood flow and vascular reactivity, as well as the interpretation of the findings, are challenging. Various methods, such as color Doppler imaging, computed tomography angiography or magnetic resonance imaging, have been employed to assess retrobulbar blood flow velocities in vivo. Color Doppler imaging represents a fast and non-invasive method to measure retrobulbar blood flow velocities in vivo. While no information about vessel diameter can be gained performing this method, computed tomography angiography and magnetic resonance imaging provide information about vessel diameter and detailed information on the anatomical course. Additionally, ex vivo studies, such as myography, utilizing genetically modified animal models may provide high optical resolution for functional vascular investigations in these small vessels. To our best knowledge, this is the first review, presenting a detailed overview of methods aiming to evaluate retrobulbar blood flow and vascular reactivity in both humans and laboratory animals. Furthermore, we will summarize the disturbances observed in retrobulbar blood flow in retinal, optic nerve, and cardiovascular diseases.
PubMed: 38066755
DOI: 10.3390/diagnostics13233514 -
ESMO Open Apr 2023Fluoropyrimidines (FPs) are an essential part of the majority of systemic regimens in the treatment of metastatic colorectal cancer (CRC). The use of the oral FP S-1 has...
BACKGROUND
Fluoropyrimidines (FPs) are an essential part of the majority of systemic regimens in the treatment of metastatic colorectal cancer (CRC). The use of the oral FP S-1 has been approved by the European Medicines Agency as monotherapy or in combination with oxaliplatin or irinotecan, with or without bevacizumab, for the treatment of patients with metastatic CRC in whom it is not possible to continue treatment with another FP due to hand-foot syndrome (HFS) or cardiovascular toxicity (CVT). Subsequently, this indication has been included in the 2022 ESMO guidelines for metastatic CRC. Recommendations for use in daily practice are not available.
PATIENTS AND METHODS
Based on peer-reviewed published data on the use of S-1 in Western patients with metastatic CRC who switched from infusional 5-fluorouracil (5-FU) or capecitabine to S-1 for reasons of HFS or CVT, recommendations for its use were formulated by an international group of medical oncologists with expertise in the treatment of metastatic CRC and a cardio-oncologist.
RESULTS
In patients who experience pain and/or functional impairment due to HFS during treatment with capecitabine or infusional 5-FU, a switch to S-1 is recommended without prior dose reduction of capecitabine/5-FU. S-1 should preferably be initiated at full dose when HFS has decreased to grade ≤1. In patients with cardiac complaints, in whom an association with capecitabine or infusional 5-FU treatment cannot be excluded, capecitabine/5-FU should be discontinued and a switch to S-1 is recommended.
CONCLUSIONS
These recommendations should guide clinicians in daily practice in the treatment of patients with metastatic CRC with FP-containing regimens.
Topics: Humans; Capecitabine; Colorectal Neoplasms; Hand-Foot Syndrome; Fluorouracil; Irinotecan; Colonic Neoplasms; Immunologic Factors
PubMed: 37018874
DOI: 10.1016/j.esmoop.2023.101199 -
Diagnostic and Interventional Imaging Oct 2012
Review
Topics: Acrocephalosyndactylia; Humans; Infant, Newborn; Male; Ultrasonography, Prenatal
PubMed: 22921691
DOI: 10.1016/j.diii.2012.06.002