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Nature Reviews. Nephrology Jul 2019X-linked hypophosphataemia (XLH) is the most common cause of inherited phosphate wasting and is associated with severe complications such as rickets, lower limb...
X-linked hypophosphataemia (XLH) is the most common cause of inherited phosphate wasting and is associated with severe complications such as rickets, lower limb deformities, pain, poor mineralization of the teeth and disproportionate short stature in children as well as hyperparathyroidism, osteomalacia, enthesopathies, osteoarthritis and pseudofractures in adults. The characteristics and severity of XLH vary between patients. Because of its rarity, the diagnosis and specific treatment of XLH are frequently delayed, which has a detrimental effect on patient outcomes. In this Evidence-Based Guideline, we recommend that the diagnosis of XLH is based on signs of rickets and/or osteomalacia in association with hypophosphataemia and renal phosphate wasting in the absence of vitamin D or calcium deficiency. Whenever possible, the diagnosis should be confirmed by molecular genetic analysis or measurement of levels of fibroblast growth factor 23 (FGF23) before treatment. Owing to the multisystemic nature of the disease, patients should be seen regularly by multidisciplinary teams organized by a metabolic bone disease expert. In this article, we summarize the current evidence and provide recommendations on features of the disease, including new treatment modalities, to improve knowledge and provide guidance for diagnosis and multidisciplinary care.
Topics: Algorithms; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Arnold-Chiari Malformation; Biomarkers; Bone Density Conservation Agents; Bone and Bones; Continuity of Patient Care; Craniosynostoses; Delphi Technique; Dental Care; Familial Hypophosphatemic Rickets; Fibroblast Growth Factor-23; Growth Hormone; Hearing Loss; Humans; Immunologic Factors; Life Style; Mutation; Orthopedic Procedures; PHEX Phosphate Regulating Neutral Endopeptidase; Phosphates; Physical Therapy Modalities; Radiography; Vitamin D
PubMed: 31068690
DOI: 10.1038/s41581-019-0152-5 -
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 -
Sudanese Journal of Paediatrics 2022
PubMed: 35958070
DOI: 10.24911/SJP.106-1594635995 -
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