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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 -
Genes Sep 2021Treacher Collins syndrome (TCS) is associated with abnormal differentiation of the first and second pharyngeal arches, occurring during fetal development. Features of... (Review)
Review
Treacher Collins syndrome (TCS) is associated with abnormal differentiation of the first and second pharyngeal arches, occurring during fetal development. Features of TCS include microtia with conductive hearing loss, slanting palpebral fissures with possibly coloboma of the lateral part of lower eyelids, midface hypoplasia, micrognathia as well as sporadically cleft palate and choanal atresia or stenosis. TCS occurs in the general population at a frequency of 1 in 50,000 live births. Four subtypes of Treacher Collins syndrome exist. TCS can be caused by pathogenic variants in the , , and genes. Genetically, the gene contains 27 exons which encodes the Treacle protein. In , over 200 pathogenic variants have been identified, of which most are deletions leading to a frame-shift, that result in the formation of a termination codon. In the presented article, we review the genetics and phenotype of TCS as well as the management and surgical procedures utilized for treatment.
Topics: Choanal Atresia; DNA-Directed RNA Polymerases; Humans; Mandibulofacial Dysostosis; Nuclear Proteins; Phosphoproteins; Syndrome
PubMed: 34573374
DOI: 10.3390/genes12091392 -
Pediatric Annals Jan 2023Along with the decrease in sudden infant death syndrome due to the successful "Back to Sleep" Campaign, there was a reciprocal increase in cases of positional... (Review)
Review
Along with the decrease in sudden infant death syndrome due to the successful "Back to Sleep" Campaign, there was a reciprocal increase in cases of positional plagiocephaly (PP). The prevalence of PP significantly rose from approximately 5% to upward of 46% at age 7 months. Consequently, clinicians have seen a surge in the number of patients presenting with head shape abnormalities. Not only does this increase in patient volume pose a logistical problem to clinics, but it also poses a potential risk to patients with craniosynostosis, whose head shape anomalies are similar to a "needle in a haystack" of patients with more common PP. This review explores the causes, risk factors, and treatment options of PP and craniosynostosis, along with the differential of head shape anomalies based on phenotypic presentation. In doing so, we hope to provide pediatric care clinicians with the tools necessary to effectively evaluate and manage patients with head shape abnormalities. .
Topics: Infant; Child; Humans; Plagiocephaly, Nonsynostotic; Craniosynostoses; Risk Factors; Sleep; Prevalence
PubMed: 36625797
DOI: 10.3928/19382359-20221114-03 -
Journal of Medical Genetics May 2022Oculo-auriculo-vertebral spectrum (OAVS) or Goldenhar syndrome is due to an abnormal development of first and second branchial arches derivatives during embryogenesis... (Review)
Review
Oculo-auriculo-vertebral spectrum (OAVS) or Goldenhar syndrome is due to an abnormal development of first and second branchial arches derivatives during embryogenesis and is characterised by hemifacial microsomia associated with auricular, ocular and vertebral malformations. The clinical and genetic heterogeneity of this spectrum with incomplete penetrance and variable expressivity, render its molecular diagnosis difficult. Only a few recurrent CNVs and genes have been identified as causatives in this complex disorder so far. Prenatal environmental causal factors have also been hypothesised. However, most of the patients remain without aetiology. In this review, we aim at updating clinical diagnostic criteria and describing genetic and non-genetic aetiologies, animal models as well as novel diagnostic tools and surgical management, in order to help and improve clinical care and genetic counselling of these patients and their families.
Topics: Animals; Branchial Region; DNA Copy Number Variations; Goldenhar Syndrome; Humans
PubMed: 35110414
DOI: 10.1136/jmedgenet-2021-108219 -
Clinical Dysmorphology Jan 2020Klippel-Feil syndrome is a congenital defect in the formation or segmentation of the cervical spine. A wide spectrum of associated anomalies may be present. This... (Review)
Review
Klippel-Feil syndrome is a congenital defect in the formation or segmentation of the cervical spine. A wide spectrum of associated anomalies may be present. This heterogeneity has complicated clarification of the genetic causes and management of patient's with congenital vertebral fusion. In this review, we focussed on clinical heterogeneity; radiographic abnormalities and genetic etiology in Klippel-Feil syndrome. We insist on comprehensive evaluation and delineation of diagnostic and prognostic classes.
Topics: Humans; Klippel-Feil Syndrome; Prognosis; Spine
PubMed: 31577545
DOI: 10.1097/MCD.0000000000000301 -
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 -
The Journal of the American Academy of... Nov 2021Klippel-Feil syndrome (KFS), or congenital fusion of the cervical vertebrae, has been thought to be an extremely rare diagnosis. However, recent literature suggests an...
Klippel-Feil syndrome (KFS), or congenital fusion of the cervical vertebrae, has been thought to be an extremely rare diagnosis. However, recent literature suggests an increased prevalence, with a high proportion of asymptomatic individuals. Occurring as a sporadic mutation or associated with several genes, the pathogenesis involves failure of cervical somite segmentation and differentiation during embryogenesis. Most commonly, the C2-C3 and C5-C6 levels are involved. KFS is associated with other orthopaedic conditions including Sprengel deformity, congenital scoliosis, and cervical spine abnormalities, as well as several visceral pathologies. There are several classification systems, some based on the anatomic levels of fusion and others on its genetic inheritance. Management of patients with KFS primarily involves observation for asymptomatic individuals. Surgical treatment may be for neurologic complaints, correction of deformity, concomitant spinal anomalies, or for associated conditions and varies significantly. Participation in sports is an important consideration. Recommendations for contact sports or activities depend on both the level and the number of vertebrae involved in the fusion. A multidisciplinary team should be involved in the treatment plan and recommendations for complex presentations.
Topics: Cervical Vertebrae; Humans; Klippel-Feil Syndrome; Scapula; Scoliosis; Shoulder Joint
PubMed: 34288888
DOI: 10.5435/JAAOS-D-21-00190 -
Neuro-Chirurgie Nov 2019
Topics: Child; Craniosynostoses; Humans
PubMed: 31699291
DOI: 10.1016/j.neuchi.2019.10.001 -
The Journal of Craniofacial Surgery Oct 2022
Topics: Craniofacial Dysostosis; Humans; Syndrome
PubMed: 35882044
DOI: 10.1097/SCS.0000000000008730 -
NeoReviews Apr 2021Craniosynostosis is the premature fusion of 1 or more sutures that normally separate the bony plates of an infant's skull and occurs in about 1 in 2,000 to 2,500 live...
Craniosynostosis is the premature fusion of 1 or more sutures that normally separate the bony plates of an infant's skull and occurs in about 1 in 2,000 to 2,500 live births. Primary or congenital craniosynostoses represent the majority of cases and consist of single-suture and multisuture synostoses. Multisuture synostoses are typically associated with distinct craniofacial syndromes, including Muenke syndrome, Apert syndrome, Crouzon syndrome, and Pfeiffer syndrome, and are thus categorized under syndromic craniosynostoses. Secondary causes of craniosynostoses include metabolic or hematologic disorders that affect bone metabolism and typically present much later than primary synostoses. The severity of the deformity and the presence of increased intracranial pressure dictate the need for early surgical intervention, prompting the importance of early recognition and timely referral. Infants with craniosynostosis are also at increased risk for neurodevelopmental impairment and thus require close follow-up and monitoring. The early recognition and referral of craniosynostosis is imperative for the optimization of management and minimization of potential neurologic impairments that may develop.
Topics: Craniofacial Dysostosis; Craniosynostoses; Humans; Infant, Newborn; Skull; Syndrome
PubMed: 33795400
DOI: 10.1542/neo.22-4-e250