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Biomechanics and Modeling in... Apr 2024Premature fusion of craniofacial joints, i.e. sutures, is a major clinical condition. This condition affects children and often requires numerous invasive surgeries to...
Premature fusion of craniofacial joints, i.e. sutures, is a major clinical condition. This condition affects children and often requires numerous invasive surgeries to correct. Minimally invasive external loading of the skull has shown some success in achieving therapeutic effects in a mouse model of this condition, promising a new non-invasive treatment approach. However, our fundamental understanding of the level of deformation that such loading has induced across the sutures, leading to the effects observed is severely limited, yet crucial for its scalability. We carried out a series of multiscale characterisations of the loading effects on normal and craniosynostotic mice, in a series of in vivo and ex vivo studies. This involved developing a custom loading setup as well as software for its control and a novel in situ CT strain estimation approach following the principles of digital volume correlation. Our findings highlight that this treatment may disrupt bone formation across the sutures through plastic deformation of the treated suture. The level of permanent deformations observed across the coronal suture after loading corresponded well with the apparent strain that was estimated. This work provides invaluable insight into the level of mechanical forces that may prevent early fusion of cranial joints during the minimally invasive treatment cycle and will help the clinical translation of the treatment approach to humans.
Topics: Humans; Child; Mice; Animals; Skull; Cranial Sutures; Craniosynostoses; Disease Models, Animal; Osteogenesis
PubMed: 38217747
DOI: 10.1007/s10237-023-01799-y -
Trials Jan 2024Mandibular distraction osteogenesis (MDO) is a major part of the treatment for hemifacial microsomia patients. Due to the narrow surgical field of the intraoral...
Efficacy of navigation system-assisted distraction osteogenesis for hemifacial microsomia based on artificial intelligence for 3 to 18 years old: study protocol for a randomized controlled single-blind trial.
BACKGROUND
Mandibular distraction osteogenesis (MDO) is a major part of the treatment for hemifacial microsomia patients. Due to the narrow surgical field of the intraoral approach, osteotomy accuracy is highly dependent on the surgeons' experience. Electromagnetic (EM) tracking systems can achieve satisfying accuracy to provide helpful real-time surgical navigation. Our research team developed an EM navigation system based on artificial intelligence, which has been justified in improving the accuracy of osteotomy in the MDO in animal experiments. This study aims to clarify the effect of the EM navigation system in improving the MDO accuracy for hemifacial microsomia patients.
METHODS
This study is designed as a single-centered and randomized controlled trial. Altogether, 22 hemifacial microsomia patients are randomly assigned to the experiment and control groups. All patients receive three-dimensional CT scans and preoperative surgical plans. The EM navigation system will be set up for those in the experiment group, and the control group will undergo traditional surgery. The primary outcome is the surgical precision by comparing the osteotomy position of pre- and postoperative CT scan images through the Geomagic Control software. The secondary outcomes include mandibular symmetry (occlusal plane deviation angle, mandibular ramus height, and body length), pain scale, and complications. Other indications, such as the adverse events of the system and the satisfactory score from patients and their families, will be recorded.
DISCUSSION
This small sample randomized controlled trial intends to explore the application of an EM navigation system in MDO for patients, which has been adopted in other surgeries such as orthognathic procedures. Because of the delicate structures of children and the narrow surgical view, accurate osteotomy and protection of nearby tissue from injury are essential for successful treatment. The EM navigation system based on artificial intelligence adopted in this trial is hypothesized to provide precise real-time navigation for surgeons and optimally improve patient outcomes, including function and aesthetic results. The results of this trial will extend the application of new navigation technology in pediatric plastic surgery.
TRIAL REGISTRATION
Chinese Clinical Trial Registry ChiCTR2200061565. Registered on 29 June 2022.
Topics: Child; Humans; Child, Preschool; Adolescent; Goldenhar Syndrome; Artificial Intelligence; Osteogenesis, Distraction; Single-Blind Method; Mandible; Randomized Controlled Trials as Topic
PubMed: 38216974
DOI: 10.1186/s13063-023-07809-9 -
Sleep & Breathing = Schlaf & Atmung Jun 2024Obstructive sleep apnea (OSA) is common in children with syndromic craniosynostosis (SC). However, objective data on the treatment of OSA in children with SC remain...
BACKGROUND
Obstructive sleep apnea (OSA) is common in children with syndromic craniosynostosis (SC). However, objective data on the treatment of OSA in children with SC remain inadequate. This study aimed to explore the efficacy of continuous positive airway pressure (CPAP) in the management of OSA in children with SC.
METHODS
A retrospective study was performed in children with SC and OSA diagnosed by polysomnography (PSG), which was defined as an apnea hypopnea index (AHI) ≥ 1. Patients were included if they were treated with CPAP and had baseline PSG and follow-up sleep studies. Clinical and demographic data were collected from all enrolled subjects.
RESULTS
A total of 45 children with SC and OSA were identified, with an average age of 6.8 ± 4.7 years. Among them, 36 cases had moderate to severe OSA (22 with severe OSA) and received CPAP therapy followed by post-treatment sleep studies. Notably, there was a significant reduction in the AHI observed after CPAP treatment (3.0 [IQR: 1.7, 4.6] versus 38.6 [IQR: 18.2, 53.3] events/h; P < 0.001).
CONCLUSIONS
CPAP is effective and acceptable in treating severe OSA in children with SC.
Topics: Humans; Sleep Apnea, Obstructive; Continuous Positive Airway Pressure; Male; Female; Craniosynostoses; Retrospective Studies; Child; Child, Preschool; Polysomnography; Treatment Outcome
PubMed: 38180682
DOI: 10.1007/s11325-023-02981-3 -
Journal of Medical Case Reports Dec 2023Klippel-Feil syndrome is a rare condition described in 1912 by Maurice Klippel and André Feil. It is defined as a congenital cervical fusion of at least two vertebrae,...
BACKGROUND
Klippel-Feil syndrome is a rare condition described in 1912 by Maurice Klippel and André Feil. It is defined as a congenital cervical fusion of at least two vertebrae, associated with a classical triad of clinical signs: short neck, low posterior hairline, and limited range of movement. However, Klippel-Feil syndrome manifests with a vast spectrum of phenotypes, ranging from no symptoms to complete triad, with or without other associated malformations. Most commonly, CCF results from sporadic mutations, even though autosomal recessive, autosomal dominant, or even X-linked inheritance can be detected. The ATP-binding cassette subfamily B member 4 is only expressed in the liver and is involved in biliary phospholipid secretion. The clinical spectrum includes various hepatobiliary pathologies, including low phospholipid-associated cholelithiasis, and has never been associated with musculoskeletal anomalies.
CASE PRESENTATION
A 55-year-old male Caucasian patient presenting with low phospholipid-associated cholelithiasis syndrome with ATP-binding cassette subfamily B member 4 mutation and liver cirrhosis was referred to our clinic for a liver transplant. A period of 6 months before, the patient underwent a T7-T9 posterior fixation for a T8 osteoporotic fracture. Postoperatively, he was tetraparetic, whereas he was neurologically intact before the operation. At admission to our hospital, he was still tetraparetic and presented with clinical signs of cervical myelopathy. Moreover, he suffered a limitation of cervical range of motion in all directions, short neck, and low posterior hairline. Imaging showed multiple cervical and thoracic vertebral bodies fusion, as well as cervical spine stenosis. Based on the available data, we diagnosed a type 3 Klippel-Feil syndrome according to Samartzis' classification.
CONCLUSIONS
The heterogeneity of KFS and the various potential hereditary links that are known indicate that it is important to highlight all potential cases related to known genetic defects. At present, no association between ATP-binding cassette subfamily B member 4 mutation and congenital cervical fusions has been reported. The other important clinical focus of this case is the appearance of spontaneous tetraparesis after thoracic spine surgery. This mechanism remains unclear, but considering different spinal anatomy it might have been due to difficult intubation and patient's positioning during his previous operation.
Topics: Male; Humans; Middle Aged; Klippel-Feil Syndrome; Cervical Vertebrae; Mutation; Cholelithiasis; Phospholipids; Adenosine Triphosphate
PubMed: 38135884
DOI: 10.1186/s13256-023-04263-8 -
Journal of Cranio-maxillo-facial... Jan 2024Craniosynostosis, characterized by premature fusion of one or more cranial sutures, results in a distorted skull shape. Only three studies have assessed facial asymmetry...
Craniosynostosis, characterized by premature fusion of one or more cranial sutures, results in a distorted skull shape. Only three studies have assessed facial asymmetry manually in unicoronal synostosis patients. It is therefore important to understand how uni- and bicoronal synostosis affect facial asymmetry with a minimum risk of human bias. An automated algorithm was developed to quantify facial asymmetry from three-dimensional images, generating a mean facial asymmetry (MFA) value in millimeters to reflect the degree of asymmetry. The framework was applied to analyze postoperative 3D images of syndromic patients (N = 35) diagnosed with Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis with respect to MFA values from a healthy control group (N = 89). Patients demonstrated substantially higher MFA values than controls: Muenke syndrome (unicoronal 1.74 ± 0.40 mm, bicoronal 0.77 ± 0.21 mm), Saethre-Chotzen syndrome (unicoronal 1.15 ± 0.20 mm, bicoronal 0.69 ± 0.16 mm), and TCF12-related craniosynostosis (unicoronal 1.40 ± 0.51 mm, bicoronal 0.66 ± 0.05 mm), compared with controls (0.49 ± 0.12 mm). Longitudinal analysis identified an increasing MFA trend in unicoronal synostosis patients. Our study revealed higher MFA in syndromic patients with uni- and bicoronal synostosis compared with controls, with the most pronounced MFA in Muenke syndrome patients with unilateral synostosis. Bicoronal synostosis patients demonstrated higher facial asymmetry than expected given the condition's symmetrical presentation.
Topics: Humans; Infant; Retrospective Studies; Facial Asymmetry; Craniosynostoses; Acrocephalosyndactylia
PubMed: 38135649
DOI: 10.1016/j.jcms.2023.11.006 -
European Journal of Medical Genetics Feb 2024LRP4 is expressed in many organs. It mediates SOST-dependent inhibition of bone formation and acts as an inhibitor of WNT signaling. It is also a postsynaptic end plate... (Review)
Review
LRP4 is expressed in many organs. It mediates SOST-dependent inhibition of bone formation and acts as an inhibitor of WNT signaling. It is also a postsynaptic end plate cell surface receptor at the neuromuscular junction and is central to its development, maintenance, and function. Pathogenic variants of LRP4 that specifically affect the canonical WNT signaling pathway are known to be associated with Cenani-Lenz syndactyly syndrome or the overlapping condition sclerosteosis. However, site-specific pathogenic variants of LRP4 have been associated with the congenital myasthenic syndrome (CMS) type 17 with no abnormal bone phenotype. Only two studies reported biallelic variants of LRP4 associated with CMS17 that presented during childhood. All three reported variants (NM_002334.4: p.Glu1233Ala, p.Glu1233Lys, or p.Arg1277His) are located within the 3'-edge of the third β-propeller domain of LRP4. We report on a patient with a biallelic variant of the LRP4 gene presenting with a severe and neonatal lethal phenotype; we also provide a literature review of the previously reported patients. A female neonate, born to healthy consanguineous parents, presented with severe hypotonia, congenital diaphragmatic hernia, pulmonary hypertension, and progressive hypoxemia. Two of her siblings presented with a similar condition in the past, and all three died shortly after birth. Clinical exome sequencing revealed homozygosity for the pathogenic variant NM_002334.4:c.3698A > C (p.[Glu1233Ala]).
Topics: Female; Humans; Infant, Newborn; Hyperostosis; LDL-Receptor Related Proteins; Myasthenic Syndromes, Congenital; Neuromuscular Junction; Syndactyly; Male
PubMed: 38101565
DOI: 10.1016/j.ejmg.2023.104903 -
Radiology Case Reports Feb 2024Jarcho-Levin syndrome (JLS) is a congenital dysostosis characterized by multiple vertebral and intrinsic rib abnormalities. JLS and neural tube abnormalities rarely...
Jarcho-Levin syndrome (JLS) is a congenital dysostosis characterized by multiple vertebral and intrinsic rib abnormalities. JLS and neural tube abnormalities rarely occur together. There have been few cases of JLS associated with a split spinal cord malformation (diastematomyelia). A dorsal dermal sinus is a tract from the skin that may end in soft tissue, epidural space, or most commonly intradural. We report the case of a 5-day-old male neonate with JLS who presented with respiratory distress immediately after birth. A chest radiograph revealed multiple bilateral asymmetric rib deformities and irregular rib fusions, multi-level segmentation defects of the thoracic vertebrae, and associated dextroconvex scoliosis of the thoracic spine. He was subsequently diagnosed with diastematomyelia, a dorsal dermal sinus, and tethered cord on ultrasound. The infant succumbed to respiratory distress from superimposed pneumonia. JLS is rarely associated with distematomyelia, and there are only ten reports worldwide. We presented the eleventh case of JLS with type 2 diastematomyelia. In addition, this is the first reported case of co-occurrence with a dorsal dermal sinus.
PubMed: 38089142
DOI: 10.1016/j.radcr.2023.11.024 -
The British Journal of Oral &... Jan 2024This review provides a comprehensive overview of the literature on velopharyngeal insufficiency, associated anomalies, and speech/language impairment in patients with... (Review)
Review
This review provides a comprehensive overview of the literature on velopharyngeal insufficiency, associated anomalies, and speech/language impairment in patients with craniofacial microsomia (CFM). A systematic search of the literature was conducted to identify records on VPI and speech impairment in CFM from their inception until September 2022 within the databases Embase, PubMed, MEDLINE, Ovid, CINAHL EBSCO, Web of Science, Cochrane, and Google Scholar. Seventeen articles were included, analysing 1,253 patients. Velopharyngeal insufficiency results in hypernasality can lead to speech impairment. The reported prevalence of both velopharyngeal insufficiency and hypernasality ranged between 12.5% and 55%, while the reported prevalence of speech impairment in patients with CFM varied between 35.4% and 74%. Language problems were reported in 37% to 50% of patients. Speech therapy was documented in 45.5% to 59.6% of patients, while surgical treatment for velopharyngeal insufficiency consisted of pharyngeal flap surgery or pharyngoplasty and was reported in 31.6% to 100%. Cleft lip and/or palate was reported in 10% to 100% of patients with CFM; these patients were found to have worse speech results than those without cleft lip and/or palate. No consensus was found on patient characteristics associated with an increased risk of velopharyngeal insufficiency and speech/language impairment. Although velopharyngeal insufficiency is a less commonly reported characteristic of CFM than other malformations, it can cause speech impairment, which may contribute to delayed language development in patients with CFM. Therefore, timely recognition and treatment of speech impairment is essential.
Topics: Humans; Cleft Lip; Cleft Palate; Goldenhar Syndrome; Language Development Disorders; Retrospective Studies; Speech; Speech Disorders; Treatment Outcome; Velopharyngeal Insufficiency
PubMed: 38057178
DOI: 10.1016/j.bjoms.2023.09.008 -
Molecular Genetics and Metabolism... Dec 2023Fucosidosis (OMIN# 230000) is a rare lysosomal storage disorder (LSDs) caused by mutations in the gene, leading to alpha-L-fucosidase deficiency; it is inherited as an...
Fucosidosis (OMIN# 230000) is a rare lysosomal storage disorder (LSDs) caused by mutations in the gene, leading to alpha-L-fucosidase deficiency; it is inherited as an autosomal recessive trait. Fucosidosis represents a disease spectrum with a wide variety of clinical features, but most affected patients have slow neurologic deterioration. Many patients die young and the long-term clinical outcomes in adult patients are poorly documented. Here, we report the long-term follow up of two Caucasian siblings, a 31-year-old man and 25-year-old woman. We describe the clinical, biochemical, radiological and genetic findings in two siblings affected by Fucosidosis and the differences between them after 19-years follow up. The dermatological features of the younger sibling have been reported previously by Bharati et al. (2007). Both patients have typical features of Fucosidosis, such as learning difficulties, ataxia, and angiokeratomas with differing severity. Case 1 presents severe ataxia with greater limitation of mobility, multiple dysostoses, angiokeratomas on his limbs, retinal vein enlargement and increased tortuosity in the eye and gastrointestinal symptoms. Biochemical analysis demonstrated a deficiency of alpha-fucosidase in leucocytes. Case 2 has a greater number of angiokeratomas and has suffered three psychotic episodes. The diagnosis of Fucosidosis was confirmed in cultured skin fibroblast at the age of 12 years. Molecular analysis of the gene showed a heterozygous mutation c.998G > A p.(Gly333Asp), with a pathogenic exon 4 deletion in the other allele in both patients. Conclusion. Fucosidosis presents a wide clinical heterogeneity and intrafamilial variability of symptoms. Psychosis and gastrointestinal symptoms have not been reported previously in Fucosidosis.
PubMed: 38053939
DOI: 10.1016/j.ymgmr.2023.101009