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Bosnian Journal of Basic Medical... May 2018Craniosynostosis is a developmental craniofacial anomaly, resulting in impairment of brain development and abnormally shaped skull. The main cause of craniosynostosis is... (Review)
Review
Craniosynostosis is a developmental craniofacial anomaly, resulting in impairment of brain development and abnormally shaped skull. The main cause of craniosynostosis is premature closure of one or more cranial sutures. It usually occurs as an isolated condition, but may also be associated with other malformations as part of complex syndromes. When left untreated, craniosynostosis can cause serious complications, such as developmental delay, facial abnormality, sensory, respiratory and neurological dysfunction, anomalies affecting the eye, and psychological disturbances. Thus, early diagnosis, expert surgical techniques, postoperative care, and adequate follow-up are of vital importance in treating craniosynostosis.
Topics: Brain; Cranial Sutures; Craniosynostoses; Developmental Disabilities; Humans; Infant; Infant, Newborn; Magnetic Resonance Imaging; Prevalence; Skull
PubMed: 28623672
DOI: 10.17305/bjbms.2017.2083 -
Disease Models & Mechanisms Apr 2022Craniosynostosis is a major congenital craniofacial disorder characterized by the premature fusion of cranial suture(s). Patients with severe craniosynostosis often have... (Review)
Review
Craniosynostosis is a major congenital craniofacial disorder characterized by the premature fusion of cranial suture(s). Patients with severe craniosynostosis often have impairments in hearing, vision, intracranial pressure and/or neurocognitive functions. Craniosynostosis can result from mutations, chromosomal abnormalities or adverse environmental effects, and can occur in isolation or in association with numerous syndromes. To date, surgical correction remains the primary treatment for craniosynostosis, but it is associated with complications and with the potential for re-synostosis. There is, therefore, a strong unmet need for new therapies. Here, we provide a comprehensive review of our current understanding of craniosynostosis, including typical craniosynostosis types, their clinical manifestations, cranial suture development, and genetic and environmental causes. Based on studies from animal models, we present a framework for understanding the pathogenesis of craniosynostosis, with an emphasis on the loss of postnatal suture mesenchymal stem cells as an emerging disease-driving mechanism. We evaluate emerging treatment options and highlight the potential of mesenchymal stem cell-based suture regeneration as a therapeutic approach for craniosynostosis.
Topics: Animals; Cranial Sutures; Craniosynostoses; Humans; Mesenchymal Stem Cells; Mutation; Syndrome
PubMed: 35451466
DOI: 10.1242/dmm.049390 -
The Veterinary Quarterly Dec 2022Brachycephalic obstructive airway syndrome (BOAS) is a chronic, lifelong, debilitating, primarily obstructive airway disease which adversely affects the quality of life... (Review)
Review
Brachycephalic obstructive airway syndrome (BOAS) is a chronic, lifelong, debilitating, primarily obstructive airway disease which adversely affects the quality of life of many popular dog breeds. Respiratory restriction in bulldog breeds, pugs and Boston terriers frequently co-exist with pathologies of the gastrointestinal tract. In addition, many brachycephalic dogs that appear clinically normal are, in fact suffering from chronic hypoxia and its systemic consequences. Concurrent gastroesophageal reflux-associated conditions, sleep disorders and systemic hypertension further impact the welfare of affected dogs. Acceptance of BOAS and associated clinical signs as being 'normal for the breed' is common amongst owners. While surgical correction of the upper airway is the mainstay of treatment, the provision of subsequent, frequently lifelong medical management is equally important for the maintenance of an acceptable quality of life, at least for some affected patients. Here we review the current knowledge concerning brachycephaly, combine it with shared clinical experience in the management of this debilitating condition, and discuss ethical considerations and the responsibility of veterinarians to contribute public education and to support appropriate breed standards for animals under our care.
Topics: Dogs; Animals; Quality of Life; Dog Diseases; Craniosynostoses; Airway Obstruction
PubMed: 36342210
DOI: 10.1080/01652176.2022.2145621 -
Cell Jan 2021Craniosynostosis results from premature fusion of the cranial suture(s), which contain mesenchymal stem cells (MSCs) that are crucial for calvarial expansion in...
Craniosynostosis results from premature fusion of the cranial suture(s), which contain mesenchymal stem cells (MSCs) that are crucial for calvarial expansion in coordination with brain growth. Infants with craniosynostosis have skull dysmorphology, increased intracranial pressure, and complications such as neurocognitive impairment that compromise quality of life. Animal models recapitulating these phenotypes are lacking, hampering development of urgently needed innovative therapies. Here, we show that Twist1 mice with craniosynostosis have increased intracranial pressure and neurocognitive behavioral abnormalities, recapitulating features of human Saethre-Chotzen syndrome. Using a biodegradable material combined with MSCs, we successfully regenerated a functional cranial suture that corrects skull deformity, normalizes intracranial pressure, and rescues neurocognitive behavior deficits. The regenerated suture creates a niche into which endogenous MSCs migrated, sustaining calvarial bone homeostasis and repair. MSC-based cranial suture regeneration offers a paradigm shift in treatment to reverse skull and neurocognitive abnormalities in this devastating disease.
Topics: Animals; Behavior, Animal; Cognition; Cranial Sutures; Craniosynostoses; Dura Mater; Gelatin; Gene Expression Profiling; Hand Strength; Intracranial Pressure; Locomotion; Mesenchymal Stem Cells; Methacrylates; Mice, Inbred C57BL; Motor Activity; Organ Size; Regeneration; Skull; Twist-Related Protein 1; Wnt Signaling Pathway; Mice
PubMed: 33417861
DOI: 10.1016/j.cell.2020.11.037 -
Neurosurgery Clinics of North America Jan 2022Hydrocephalus, the abnormal accumulation and impaired circulation/clearance of cerebrospinal fluid, occurs as a common phenotypic feature of a diverse group of genetic... (Review)
Review
Hydrocephalus, the abnormal accumulation and impaired circulation/clearance of cerebrospinal fluid, occurs as a common phenotypic feature of a diverse group of genetic syndromes. In this review, we outline the genetic mutations, pathogenesis, and accompanying symptoms underlying syndromic hydrocephalus in the context of: L1 syndrome, syndromic craniosynostoses, achondroplasia, NF 1/2, Down's syndrome, tuberous sclerosis, Walker-Warburg syndrome, primary ciliary dyskinesia, and osteogenesis imperfecta. Further, we discuss emerging genetic variants associated with syndromic hydrocephalus.
Topics: Craniosynostoses; Humans; Hydrocephalus; Syndrome
PubMed: 34801143
DOI: 10.1016/j.nec.2021.09.006 -
Journal of Comparative Pathology Apr 2020Brachycephalic dog breeds have experienced a marked rise in popularity in recent years. While numerous people clearly desire this phenotype in their pets, many of these... (Review)
Review
Brachycephalic dog breeds have experienced a marked rise in popularity in recent years. While numerous people clearly desire this phenotype in their pets, many of these dogs unfortunately experience several concomitant sequelae, including major problems with respiration and thermoregulation, as well as gastrointestinal, ophthalmological, dermatological, reproductive and even dental problems. This mini review focuses on the anatomical and pathological changes associated with brachycephalic skull shape, including brachycephalic obstructive airway syndrome and other co-existent disorders. It then details the known genetic contributors to brachycephaly, and concludes with a brief discourse on the welfare of these animals.
Topics: Animals; Craniosynostoses; Dog Diseases; Dogs
PubMed: 32359622
DOI: 10.1016/j.jcpa.2020.02.008 -
Nature Sep 2023Craniosynostosis is a group of disorders of premature calvarial suture fusion. The identity of the calvarial stem cells (CSCs) that produce fusion-driving osteoblasts in...
Craniosynostosis is a group of disorders of premature calvarial suture fusion. The identity of the calvarial stem cells (CSCs) that produce fusion-driving osteoblasts in craniosynostosis remains poorly understood. Here we show that both physiologic calvarial mineralization and pathologic calvarial fusion in craniosynostosis reflect the interaction of two separate stem cell lineages; a previously identified cathepsin K (CTSK) lineage CSC (CTSK CSC) and a separate discoidin domain-containing receptor 2 (DDR2) lineage stem cell (DDR2 CSC) that we identified in this study. Deletion of Twist1, a gene associated with craniosynostosis in humans, solely in CTSK CSCs is sufficient to drive craniosynostosis in mice, but the sites that are destined to fuse exhibit an unexpected depletion of CTSK CSCs and a corresponding expansion of DDR2 CSCs, with DDR2 CSC expansion being a direct maladaptive response to CTSK CSC depletion. DDR2 CSCs display full stemness features, and our results establish the presence of two distinct stem cell lineages in the sutures, with both populations contributing to physiologic calvarial mineralization. DDR2 CSCs mediate a distinct form of endochondral ossification without the typical haematopoietic marrow formation. Implantation of DDR2 CSCs into suture sites is sufficient to induce fusion, and this phenotype was prevented by co-transplantation of CTSK CSCs. Finally, the human counterparts of DDR2 CSCs and CTSK CSCs display conserved functional properties in xenograft assays. The interaction between these two stem cell populations provides a new biologic interface for the modulation of calvarial mineralization and suture patency.
Topics: Humans; Mice; Animals; Craniosynostoses; Osteogenesis; Cell Lineage; Phenotype; Stem Cells
PubMed: 37730988
DOI: 10.1038/s41586-023-06526-2 -
American Journal of Medical Genetics.... May 2017Craniosynostosis, the premature ossification of one or more skull sutures, is a clinically and genetically heterogeneous congenital anomaly affecting approximately one... (Review)
Review
Craniosynostosis, the premature ossification of one or more skull sutures, is a clinically and genetically heterogeneous congenital anomaly affecting approximately one in 2,500 live births. In most cases, it occurs as an isolated congenital anomaly, that is, nonsyndromic craniosynostosis (NCS), the genetic, and environmental causes of which remain largely unknown. Recent data suggest that, at least some of the midline NCS cases may be explained by two loci inheritance. In approximately 25-30% of patients, craniosynostosis presents as a feature of a genetic syndrome due to chromosomal defects or mutations in genes within interconnected signaling pathways. The aim of this review is to provide a detailed and comprehensive update on the genetic and environmental factors associated with NCS, integrating the scientific findings achieved during the last decade. Focus on the neurodevelopmental, imaging, and treatment aspects of NCS is also provided.
Topics: Congenital Abnormalities; Cranial Sutures; Craniosynostoses; Humans; Ossification, Heterotopic; Phenotype
PubMed: 28160402
DOI: 10.1002/ajmg.a.38159 -
Neuro-Chirurgie Nov 2019The aim of this review was to report on recent advances in trigonocephaly since the last report on craniosynostosis published in 2006. (Review)
Review
INTRODUCTION
The aim of this review was to report on recent advances in trigonocephaly since the last report on craniosynostosis published in 2006.
MATERIAL AND METHODS
The review was conducted in accordance with the PRISMA guidelines. Research focused on four main topics: epidemiology, neurodevelopmental disorders, genetics and surgical techniques.
RESULTS
Forty reports were included. The prevalence of trigonocephaly increased during the last two decades both in Europe and in the United States, but no clear contributing factors have yet been identified. Neurodevelopmental disorders are frequent in syndromic trigonocephaly and not particularly rare in non-syndromic cases (up to 34%). Developmental retardation (speech, motor or global) was almost always present in children exposed to valproic acid. Chromosomal abnormalities described in metopic synostosis comprised deletion of chromosome 11q24, deletion or trisomy of 9p and deletion of 7p, deletions of 3q, 13q, 12pter, 22q11, and duplication of 15q25. SMAD6 mutations should be systematically screened for in familial cases. Recent advances in surgical techniques have mainly concerned endoscopic-assisted procedures, as they significantly reduce perioperative morbidity.
CONCLUSIONS
Neurosurgeons, maxillofacial and plastic surgeons will be increasingly concerned with trigonocephaly because of the increase in prevalence observed over the last two decades. Cytogenetic alterations are probably underestimated in this craniosynostosis, considering the high rate of neurodevelopmental retardation compared to other single-suture synostoses. Genetic counselling is therefore more and more effective in this pathology. An objective method to evaluate the cosmetic results of both endoscopic and open surgeries is necessary, as some under-corrections have been reported with minimally invasive surgery.
Topics: Anticonvulsants; Child; Child, Preschool; Craniosynostoses; Humans; Infant; Infant, Newborn; Intellectual Disability; Mass Screening; Plastic Surgery Procedures; Valproic Acid
PubMed: 31568780
DOI: 10.1016/j.neuchi.2019.09.014 -
Indian Journal of Ophthalmology Jul 2022The current literature review aims to evaluate the ocular findings and associated ophthalmic features in Crouzon syndrome. Craniosynostoses are syndromes characterized... (Review)
Review
The current literature review aims to evaluate the ocular findings and associated ophthalmic features in Crouzon syndrome. Craniosynostoses are syndromes characterized by premature fusion of sutures of the skull and Crouzon syndrome is the most common of the craniosynostosis syndromes. Early fusion of sutures results in craniofacial anomalies, including abnormalities of the orbits. To prepare this review of the ophthalmic findings in this disorder, an organized search on online databases such as PubMed, Scopus, Cochrane Library, and Ovid was carried out. The key terms searched were "Crouzon", "craniosynostosis", "eye" and "ophthalmic", and 51 research items were found. A total of 17 articles were included after scrutiny of the databases and a further 25 articles were added after augmented search. A detailed review was performed from the final 42 articles. A comprehensive description of associated anomalies is given along with the author's own technique of surgical management in cases with Crouzon syndrome having bilateral luxation bulbi with exposure keratopathy. However, for optimum management of cranial and oculo-facial dysmorphisms, a multidisciplinary team of specialists is required.
Topics: Craniofacial Dysostosis; Craniosynostoses; Eye; Face; Humans; Syndrome
PubMed: 35791116
DOI: 10.4103/ijo.IJO_3207_21