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Journal of Pharmacy & Bioallied Sciences Apr 2024Pycnodysostosis is an inherited autosomal recessive disorder characterized by dysplasia of the skeletal system. It occurs in any human races with no disparity in gender...
Pycnodysostosis is an inherited autosomal recessive disorder characterized by dysplasia of the skeletal system. It occurs in any human races with no disparity in gender or age predilection. The disease is diagnosed at a young age owing to the frequent fragile bone fractures. Craniofacial and dental manifestations may overlap with those of other craniofacial dysostosis; therefore, precise knowledge is essential in differential diagnosis as it may affect the treatment outcome. Here, we report three cases with typical clinical and radiological features, among which one presented with osteomyelitis of the mandible.
PubMed: 38882744
DOI: 10.4103/jpbs.jpbs_1203_23 -
Radiology Case Reports Aug 2024Spondylocostal dysostosis (Jarcho Levin syndrome) is a rare costovertebral malformation syndrome that will result in restrictive pulmonary physiology. It manifests its...
Spondylocostal dysostosis (Jarcho Levin syndrome) is a rare costovertebral malformation syndrome that will result in restrictive pulmonary physiology. It manifests its major components at birth. Split cord malformation, together with spondylocostal dysostosis, is even rarer. We hereby report our experience with diagnosing 1 infant with spondylocostal dysostosis and type II split cord malformation using computed tomography and magnetic resonance imaging. We also present a concise summary of previously published case reports and case series involving patients with concurrent spondylocostal dysostosis and split cord malformations.
PubMed: 38860271
DOI: 10.1016/j.radcr.2024.04.095 -
Medicine Jun 2024Crouzon syndrome is an extremely rare craniofacial dysplasia, which is mainly caused by the early ossification and closure of the coronal suture of the skull.... (Review)
Review
RATIONALE
Crouzon syndrome is an extremely rare craniofacial dysplasia, which is mainly caused by the early ossification and closure of the coronal suture of the skull. Craniofacial deformities can cause stenosis of the nasal cavity and posterior nasal meatus, resulting in sleep apnea.
PATIENT CONCERNS
A 9-year-old boy with sleep snoring for 6 years, progressive aggravation in the past 1 month and accompanied by apnea during sleep.
DIAGNOSES
This case was diagnosed with Crouzon syndrome complicated with severe obstructive sleep apnea and severe hypoxemia.
INTERVENTIONS
After adenoidectomy, he was admitted to the pediatric intensive care unit with ventilator-assisted respiration. During this period, the blood oxygen saturation fluctuated greatly. After trying to extubate, the blood oxygen was difficult to maintain and had to be intubated again. After active treatment, extubation was successful.
OUTCOMES
The wound of nasopharynx recovered well and the sleep state was significantly improved 3 months postoperation.
LESSONS
It is suggested that the time of ventilator-assisted breathing should be prolonged and the perioperative airway management should be strengthened in order to reduce the risk of postoperative complications.
Topics: Child; Humans; Male; Adenoidectomy; Craniofacial Dysostosis; Respiration, Artificial; Sleep Apnea, Obstructive
PubMed: 38847734
DOI: 10.1097/MD.0000000000038534 -
Archives of Razi Institute Dec 2023Klippel-Feil Syndrome (KFS) is a rare genetic disorder characterized by the abnormal development of the cervical spine, leading to the fusion of two or more cervical...
Klippel-Feil Syndrome (KFS) is a rare genetic disorder characterized by the abnormal development of the cervical spine, leading to the fusion of two or more cervical vertebrae. The syndrome presents diverse symptoms, including limited neck movement, chronic pain, and neurological manifestations such as limb numbness or weakness. The severity of KFS can vary significantly, and treatment primarily focuses on symptom management and preventing complications such as scoliosis or spinal cord compression. Surgical interventions are often necessary for patients with complex forms of the syndrome. Interestingly, Chiari 1 malformation, a cranial anomaly affecting the brainstem, can coincide anatomically with KFS. In this case report, we present the case of a 9-year-old patient who sought medical attention due to persistent, unchanging neck pain. The patient's medical history was notable for developmental delays and cervical restraint observed during physical examination. Magnetic resonance imaging (MRI) findings revealed hydrocephalus and brainstem descent, indicating the presence of Chiari 1 malformation. Comprehensive MRI and CT scans were performed, and a management plan was formulated, primarily involving cranial surgery and physiotherapy. Implementation of the treatment approach resulted in significant improvement in the patient's symptoms. This case highlights the significance of considering Chiari 1 malformation as a potential comorbidity in patients diagnosed with KFS who present with persistent neck pain. Early detection and appropriate management of both conditions are crucial for achieving favorable outcomes and enhancing the quality of life for affected individuals. Understanding the complex interplay between KFS and Chiari 1 malformation is essential for providing comprehensive care and tailored treatment strategies. Further research is warranted to elucidate the underlying mechanisms linking these two conditions and to explore optimal management approaches for patients with dual pathology. By reporting this case, we contribute to the existing literature and increase awareness among healthcare professionals regarding the potential coexistence of KFS and Chiari 1 malformation. Continued efforts in identifying associated anomalies and optimizing therapeutic interventions will aid in improving patient outcomes and ensuring optimal care for individuals affected by these conditions.
Topics: Klippel-Feil Syndrome; Humans; Child; Magnetic Resonance Imaging; Arnold-Chiari Malformation; Male; Tomography, X-Ray Computed; Neck Pain; Female
PubMed: 38828178
DOI: 10.32592/ARI.2023.78.6.1868 -
Stem Cell Research Aug 2024Rubinstein Taybi Syndrome (RSTS) is a rare genetic disorder which is caused by mutations in either CREBBP or EP300. RSTS with mutations in CREBBP is known as RSTS-1. We...
Rubinstein Taybi Syndrome (RSTS) is a rare genetic disorder which is caused by mutations in either CREBBP or EP300. RSTS with mutations in CREBBP is known as RSTS-1. We have generated an induced pluripotent stem cell (iPSC) line, IGIBi018-A from an Indian RSTS-patient using the episomal reprogramming method. The CREBBP gene in the patient harbours a nonsense mutation at position NM_004380.3(c.6876 del C). IGIBi018-A iPSC showed expression of pluripotent stem cell markers, has a normal karyotype and could be differentiated into three germ layers. This iPSC line will help to explore the role of CREBBP in RSTS associated developmental defects.
Topics: Humans; Induced Pluripotent Stem Cells; Rubinstein-Taybi Syndrome; Cell Line; Cell Differentiation; India; Male; CREB-Binding Protein
PubMed: 38820863
DOI: 10.1016/j.scr.2024.103456 -
Computers in Biology and Medicine Jul 2024Endoscopic strip craniectomy followed by helmet therapy (ESCH) is a minimally invasive approach for correcting sagittal craniosynostosis. The treatment involves a...
BACKGROUND
Endoscopic strip craniectomy followed by helmet therapy (ESCH) is a minimally invasive approach for correcting sagittal craniosynostosis. The treatment involves a patient-specific helmet designed to facilitate lateral growth while constraining sagittal expansion. In this study, finite element modelling was used to predict post-treatment head reshaping, improving our comprehension of the necessary helmet therapy duration.
METHOD
Six patients (aged 11 weeks to 9 months) who underwent ESCH at Connecticut Children's Hospital were enrolled in this study. Day-1 post-operative 3D scans were used to create skin, skull, and intracranial volume models. Patient-specific helmet models, incorporating areas for growth, were designed based on post-operative imaging. Brain growth was simulated through thermal expansion, and treatments were modelled according to post-operative Imaging available. Mechanical testing and finite element modelling were combined to determine patient-specific mechanical properties from bone samples collected from surgery. Validation compared simulated end-of-treatment skin surfaces with optical scans in terms of shape matching and cranial index estimation.
RESULTS
Comparison between the simulated post-treatment head shape and optical scans showed that on average 97.3 ± 2.1 % of surface data points were within a distance range of -3 to 3 mm. The cranial index was also accurately predicted (r = 0.91).
CONCLUSIONS
In conclusion, finite element models effectively predicted the ESCH cranial remodeling outcomes up to 8 months postoperatively. This computational tool offers valuable insights to guide and refine helmet treatment duration. This study also incorporated patient-specific material properties, enhancing the accuracy of the modeling approach.
Topics: Humans; Craniosynostoses; Infant; Head Protective Devices; Male; Female; Craniotomy; Computer Simulation; Finite Element Analysis; Endoscopy; Head
PubMed: 38805810
DOI: 10.1016/j.compbiomed.2024.108633 -
Medicina (Kaunas, Lithuania) May 2024Klippel-Feil syndrome (KFS) is characterized by the congenital fusion of the cervical vertebrae and is sometimes accompanied by anomalies in the craniocervical junction....
Klippel-Feil syndrome (KFS) is characterized by the congenital fusion of the cervical vertebrae and is sometimes accompanied by anomalies in the craniocervical junction. In basilar invagination (BI), which is a dislocation of the dens in an upper direction, compression of the brainstem and cervical cord results in neurological defects and surgery is required. A 16-year-old boy diagnosed with KFS and severe BI presented with spastic tetraplegia, opisthotonus and dyspnea. CT scans showed basilar impression, occipitalization of C1 and fusion of C2/C3. MRI showed ventral compression of the medullocervical junction. Posterior occipitocervical reduction and fusion along with decompression were performed. Paralysis gradually improved postoperatively over 3 weeks. However, severe spasticity and opisthotonus persisted and intrathecal baclofen (ITB) therapy was initiated. Following this, opisthotonus disappeared and spasticity of the extremities improved. Rehabilitation therapy continued by controlling the dose of ITB. Five years after the surgery, self-propelled wheelchair driving was achieved and activities of daily life improved. The treatment strategy for patients with BI and congenital anomalies remains controversial. Posterior reduction and internal fixation using instrumentation were effective techniques in this case. Spasticity control achieved through a combination of surgery and ITB treatment enabled the amelioration of therapeutic efficacy of rehabilitation and the improvement of ADL.
Topics: Humans; Baclofen; Male; Klippel-Feil Syndrome; Adolescent; Cervical Vertebrae; Spinal Fusion; Injections, Spinal; Muscle Relaxants, Central; Occipital Bone; Treatment Outcome; Decompression, Surgical
PubMed: 38792938
DOI: 10.3390/medicina60050755 -
Orphanet Journal of Rare Diseases May 2024Trigonocephaly occurs due to the premature fusion of the metopic suture, leading to a triangular forehead and hypotelorism. This condition often requires surgical...
BACKGROUND
Trigonocephaly occurs due to the premature fusion of the metopic suture, leading to a triangular forehead and hypotelorism. This condition often requires surgical correction for morphological and functional indications. Metopic ridges also originate from premature metopic closure but are only associated with mid-frontal bulging; their surgical correction is rarely required. Differential diagnosis between these two conditions can be challenging, especially in minor trigonocephaly.
METHODS
Two hundred seven scans of patients with trigonocephaly (90), metopic rigdes (27), and controls (90) were collected. Geometric morphometrics were used to quantify skull and orbital morphology as well as the interfrontal angle and the cephalic index. An innovative method was developed to automatically compute the frontal curvature along the metopic suture. Different machine-learning algorithms were tested to assess the predictive power of morphological data in terms of classification.
RESULTS
We showed that control patients, trigonocephaly and metopic rigdes have distinctive skull and orbital shapes. The 3D frontal curvature enabled a clear discrimination between groups (sensitivity and specificity > 92%). Furthermore, we reached an accuracy of 100% in group discrimination when combining 6 univariate measures.
CONCLUSION
Two diagnostic tools were proposed and demonstrated to be successful in assisting differential diagnosis for patients with trigonocephaly or metopic ridges. Further clinical assessments are required to validate the practical clinical relevance of these tools.
Topics: Humans; Craniosynostoses; Female; Male; Infant; Imaging, Three-Dimensional; Skull
PubMed: 38762603
DOI: 10.1186/s13023-024-03197-8 -
Human Genetics Jun 2024Histone deacetylases (HDACs) are enzymes pivotal for histone modification (i.e. acetylation marks removal), chromatin accessibility and gene expression regulation. Class...
Histone deacetylases (HDACs) are enzymes pivotal for histone modification (i.e. acetylation marks removal), chromatin accessibility and gene expression regulation. Class I HDACs (including HDAC1, 2, 3, 8) are ubiquitously expressed and they often participate in multi-molecular protein complexes. To date, three neurodevelopmental disorders caused by mutations in genes encoding for HDACs (HDAC4, HDAC6 and HDAC8) and thus belonging to the group of chromatinopathies, have been described. We performed whole exome sequencing (WES) for a patient (#249) clinically diagnosed with the chromatinopathy Rubinstein-Taybi syndrome (RSTS) but negative for mutations in RSTS genes, identifying a de novo frameshift variant in HDAC2 gene. We then investigated its molecular effects in lymphoblastoid cell lines (LCLs) derived from the patient compared to LCLs from healthy donors (HD). As the variant was predicted to be likely pathogenetic and to affect the sequence of nuclear localization signal, we performed immunocytochemistry and lysates fractionation, observing a nuclear mis-localization of HDAC2 compared to HD LCLs. In addition, HDAC2 total protein abundance resulted altered in patient, and we found that newly identified variant in HDAC2 affects also acetylation levels, with significant difference in acetylation pattern among patient #249, HD and RSTS cells and in expression of a known molecular target. Remarkably, RNA-seq performed on #249, HD and RSTS cells shows differentially expressed genes (DEGs) common to #249 and RSTS. Interestingly, our reported patient was clinically diagnosed with RSTS, a chromatinopathy which known causative genes encode for enzymes antagonizing HDACs. These results support the role of HDAC2 as causative gene for chromatinopathies, strengthening the genotype-phenotype correlations in this relevant group of disorders.
Topics: Humans; Histone Deacetylase 2; Exome Sequencing; Acetylation; Rubinstein-Taybi Syndrome; Chromatin; Male; Female; Mutation; Frameshift Mutation; Cell Line
PubMed: 38753158
DOI: 10.1007/s00439-024-02675-0