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BMC Neurology Mar 2024RARS2-related mitochondrial disorder is an autosomal recessive mitochondrial encephalopathy caused by biallelic pathogenic variants in the gene encoding the...
BACKGROUND
RARS2-related mitochondrial disorder is an autosomal recessive mitochondrial encephalopathy caused by biallelic pathogenic variants in the gene encoding the mitochondrial arginyl-transfer RNA synthetase 2 (RARS2, MIM *611524, NM_020320.5). RARS2 catalyzes the transfer of L-arginine to its cognate tRNA during the translation of mitochondrially-encoded proteins. The classical presentation of RARS2-related mitochondrial disorder includes pontocerebellar hypoplasia (PCH), progressive microcephaly, profound developmental delay, feeding difficulties, and hypotonia. Most patients also develop severe epilepsy by three months of age, which consists of focal or generalized seizures that frequently become pharmacoresistant and lead to developmental and epileptic encephalopathy (DEE).
CASE PRESENTATION
Here, we describe a six-year-old boy with developmental delay, hypotonia, and failure to thrive who developed an early-onset DEE consistent with Lennox-Gastaut Syndrome (LGS), which has not previously been observed in this disorder. He had dysmorphic features including bilateral macrotia, overriding second toes, a depressed nasal bridge, retrognathia, and downslanting palpebral fissures, and he did not demonstrate progressive microcephaly. Whole genome sequencing identified two variants in RARS2, c.36 + 1G > T, a previously unpublished variant that is predicted to affect splicing and is, therefore, likely pathogenic and c.419 T > G (p.Phe140Cys), a known pathogenic variant. He exhibited significant, progressive generalized brain atrophy and ex vacuo dilation of the supratentorial ventricular system on brain MRI and did not demonstrate PCH. Treatment with a ketogenic diet (KD) reduced seizure frequency and enabled him to make developmental progress. Plasma untargeted metabolomics analysis showed increased levels of lysophospholipid and sphingomyelin-related metabolites.
CONCLUSIONS
Our work expands the clinical spectrum of RARS2-related mitochondrial disorder, demonstrating that patients can present with dysmorphic features and an absence of progressive microcephaly, which can help guide the diagnosis of this condition. Our case highlights the importance of appropriate seizure phenotyping in this condition and indicates that patients can develop LGS, for which a KD may be a viable therapeutic option. Our work further suggests that analytes of phospholipid metabolism may serve as biomarkers of mitochondrial dysfunction.
Topics: Humans; Male; Child; Microcephaly; Muscle Hypotonia; Phenotype; Mitochondrial Diseases; Seizures; Arginine-tRNA Ligase
PubMed: 38438854
DOI: 10.1186/s12883-024-03571-w -
World Neurosurgery May 2024This study aimed to examine pneumatization and topographic location of the posterior clinoid process (PCP) in Chiari type I malformation (CIM) for skull base approaches.
OBJECTIVE
This study aimed to examine pneumatization and topographic location of the posterior clinoid process (PCP) in Chiari type I malformation (CIM) for skull base approaches.
METHODS
Computed tomography images of 52 (23 males/29 females) CIM subjects aged 23.87 ± 16.09 years and 71 (26 males/45 females) healthy subjects aged 42.48 ± 21.48 years constituted the study universe.
RESULTS
The distances of PCP to the foramen magnum (P = 0.037), superior orbital fissure (P < 0.001), foramen rotundum (P < 0.001), and foramen ovale (P < 0.001) were smaller, but the distance of PCP to the crista galli (P = 0.038) was greater in CIM patients, compared with normal subjects. In CIM, the fusion between PCP and the anterior clinoid process was observed in 9 sides (8.70%), while in controls it was observed in 12 sides (8.50%). PCP pneumatization was observed in 40 sides (38.50%) in CIM patients, while it was observed in 28 sides (19.70%) in normal subjects. These data displayed that PCP pneumatization was affected by CIM (P < 0.001).
CONCLUSIONS
The distances of PCP to the crista galli and foramen magnum indicate the anterior fossa length and the posterior fossa depth, respectively; thus CIM patients have a longer anterior fossa and a shallow posterior fossa. In addition, the distances of PCP to the superior orbital fissure, foramen rotundum, and foramen ovale indicate the middle fossa width; hence CIM patients have less middle fossa width than normal individuals. CIM patients have an approximately 50% higher PCP pneumatization rate, and this may increase the risk of complications such as cerebrospinal fluid fistula during the application of posterior clinoidectomy.
Topics: Humans; Arnold-Chiari Malformation; Male; Female; Adult; Young Adult; Tomography, X-Ray Computed; Adolescent; Middle Aged; Skull Base; Foramen Magnum; Sphenoid Bone
PubMed: 38431212
DOI: 10.1016/j.wneu.2024.02.130 -
Cureus Jan 2024Dupuytren's disease (DD) is a fibroproliferative disorder that manifests as an abnormal growth of myofibroblasts, causing nodule formation and contractures and affecting... (Review)
Review
Comparing Complications and Patient Satisfaction Following Injectable Collagenase Versus Limited Fasciectomy for Dupuytren's Disease: A Systematic Review and Meta-Analysis.
Dupuytren's disease (DD) is a fibroproliferative disorder that manifests as an abnormal growth of myofibroblasts, causing nodule formation and contractures and affecting digit function. If left untreated, these contractures can lead to a loss of mobility and potentially impact hand function. This systematic review critically compares and evaluates the existing literature on the complications and patient satisfaction following injectable collagenase (CCH) versus limited fasciectomy (LF) for DD. We performed a comprehensive search of the PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), The Cochrane Library, and Excerpta Medica database (EMBASE) databases from 2006 to August 2023. This research targeted all clinical studies involving adults who underwent injectable collagenase and/or limited fasciectomy in the management of DD. Out of the 437 identified studies, only 53 were considered eligible for our analysis, and merely 14 met our inclusion criteria. These selected studies encompassed a total of 967 patients with 1,344 treated joints, with an average follow-up duration of 19.22 (ranging from one to 84.06) months. Within this cohort, 498 joints from 385 patients underwent LF, while 846 joints from 491 patients received CCH injections. Notably, among the 491 patients treated with CCH, 1,060 complications were reported, averaging 2.15 complications per patient, with the most common being contusion/bruising/hematoma/ecchymosis (22.54%), and edema/swelling (18.96%). In contrast, among the 385 patients treated with LF, only 97 complications were reported, translating to 0.25 complications per patient, with the most frequent being paraesthesia or numbness (23.7%), scar sequelae like skin laceration, tear, fissure, or hypertrophic scar (23.7%), and neuropraxia or nerve injury (22.6%). Our meta-analysis indicates that paraesthesia or numbness is more frequently observed in LF than CCH injections, although without statistical significance, with a risk ratio (RR) of 0.39 (95% confidence interval (CI) 0.13-1.18, p-value 0.1). However, scar sequelae (hypertrophic scar, skin laceration, tear, or fissure) show a contrasting pattern, being more commonly associated with CCH injections than LF, with an RR of 1.98 (95% CI 0.26-14.85, p-value 0.51), which, upon eliminating the source of heterogeneity, becomes statistically significant, with an RR of 4.98 (95% CI 1.40-17.72, p-value 0.01). Our data revealed a higher frequency of complications with CCH compared to LF, although more severe adverse effects were observed in the LF group, such as neuropraxia or nerve injury. Scar sequelae were more common with CCH injections. Despite both treatments showing increased patient satisfaction at the final follow-up, CCH injection resulted in earlier improvements in satisfaction.
PubMed: 38420076
DOI: 10.7759/cureus.53147 -
Molecular Genetics & Genomic Medicine Feb 2024TNRC6B deficiency syndrome, also known as global developmental delay with speech and behavioral abnormalities (MIM 619243), is a rare autosomal dominant genetic disease...
Novel variants in TNRC6B cause global developmental delay with speech and behavioral abnormalities, short stature, low body weight, café-au-lait spots, and metabolic abnormality.
BACKGROUND
TNRC6B deficiency syndrome, also known as global developmental delay with speech and behavioral abnormalities (MIM 619243), is a rare autosomal dominant genetic disease mainly characterized by facial dysmorphism, developmental delay/intellectual disability (DD/ID), speech and language delay, fine and motor delay, attention deficit and hyperactivity disorder (ADHD), and variable behavioral abnormalities. It is caused by heterozygous variant in the TNRC6B gene (NM_001162501.2, MIM 610740), which encodes the trinucleotide repeat-containing adaptor 6B protein.
METHODS
In this study, two Chinese patients with TNRC6B deficiency syndrome were recruited, and genomic DNA extraction from peripheral blood leukocytes of these parents and their family members was extracted for whole-exome sequencing and Sanger sequencing.
RESULTS
Here, we report two unrelated Chinese patients diagnosed with TNRC6B deficiency syndrome caused by novel de novo likely pathogenic or pathogenic TNRC6B variants c.335C>T (p.Pro112Leu) and c.1632delC (p.Leu546fs*63), which expands the genetic spectrum of TNRC6B deficiency syndrome. The clinical features of the patients were DD/ID, delayed speech, ADHD, behavioral abnormalities, short stature, low body weight, café-au-lait spots, metabolic abnormalities, and facial dysmorphism including coarse facial features, sparse hair, frontal bossing, hypertelorism, amblyopia, strabismus, and downslanted palpebral fissures, which expands the phenotype spectrum associated with TNRC6B deficiency syndrome.
CONCLUSION
This study expands the genotypic and phenotypic spectrum of TNRC6B deficiency syndrome. Our findings indicate that patients with TNRC6B deficiency syndrome should be monitored for growth and metabolic problems and therapeutic strategies should be developed to address these problems. Our report also suggests the clinical diversity of TNRC6B deficiency syndrome.
Topics: Humans; Body Weight; Cafe-au-Lait Spots; Intellectual Disability; Musculoskeletal Abnormalities; RNA-Binding Proteins; Speech
PubMed: 38404251
DOI: 10.1002/mgg3.2408 -
Journal of Ayub Medical College,... 2023Optic disc pits are hypothesized to form because of failure of embryonic fissure closure, which can also present with congenital defects in the choroid, RPE, and... (Review)
Review
Optic disc pits are hypothesized to form because of failure of embryonic fissure closure, which can also present with congenital defects in the choroid, RPE, and neurosensory retina. It is also associated with serous macular detachment. We present a case report of a 32-year-old man with an optic disc pit and independent choroidal coloboma below the inferior peripapillary area in the left eye, associated with macular retinoschisis with serous detachment.
Topics: Adult; Humans; Male; Coloboma; Eye Abnormalities; Optic Disk; Retinal Detachment; Retinoschisis
PubMed: 38404105
DOI: 10.55519/JAMC-03-11574 -
International Journal of Surgery Case... Mar 2024Abnormal branching of the pulmonary artery is often encountered in anatomical lung resection, which can potentially result in accidental vessel injury with...
INTRODUCTION
Abnormal branching of the pulmonary artery is often encountered in anatomical lung resection, which can potentially result in accidental vessel injury with life-threatening bleeding or extra lung resection. The mediastinal basal pulmonary artery (Arteria Praebronchialis, AP) is a very rare but potentially critical variant.
PRESENTATION OF CASE
We present the case of a patient with lung cancer accompanied by the left basal segmental pulmonary artery, independent A, which was liable to be injured during lower lobectomy with poor interlobar fissure development. This variation was preoperatively recognized using three-dimensional contrast-enhanced computed tomography (3D-CECT) angiography, and vessel injury was avoided.
DISCUSSION AND LITERATURE REVIEW
3D-CECT angiography was effective in identifying this rare but potentially critical variation, and it is desirable to perform it routinely before anatomical lung resection. A review of 31 AP cases revealed that the branching pattern of AP was independent (15 patients, 48 %) and common trunk type (16 patients, 52 %), one half for each. Mediastinal branching of the lingular artery was more frequent among the reported AP cases (71 %) than in general reports.
CONCLUSION
When mediastinal branches of left pulmonary artery are encountered, the possibility that it is AP should be always taken into account.
PubMed: 38394937
DOI: 10.1016/j.ijscr.2024.109394 -
American Journal of Medical Genetics.... Jul 2024Biallelic variants in the OTUD6B gene have been reported in the literature in association with an intellectual developmental disorder featuring dysmorphic facies,... (Review)
Review
Biallelic variants in the OTUD6B gene have been reported in the literature in association with an intellectual developmental disorder featuring dysmorphic facies, seizures, and distal limb abnormalities. Physical differences described for affected individuals suggest that the disorder may be clinically recognizable, but previous publications have reported an initial clinical suspicion for Kabuki syndrome (KS) in some affected individuals. Here, we report on three siblings with biallelic variants in OTUD6B co-segregating with neurodevelopmental delay, shared physical differences, and other clinical findings similar to those of previously reported individuals. However, clinical manifestations such as long palpebral fissures, prominent and cupped ears, developmental delay, growth deficiency, persistent fetal fingertip pads, vertebral anomaly, and seizures in the proband were initially suggestive of KS. In addition, previously unreported clinical manifestations such as delayed eruption of primary dentition, soft doughy skin with reduced sweating, and mirror movements present in our patients suggest an expansion of the phenotype, and we perform a literature review to update on current information related to OTUD6B and human gene-disease association.
Topics: Child; Child, Preschool; Humans; Male; Abnormalities, Multiple; Alleles; Endopeptidases; Face; Genetic Association Studies; Genetic Predisposition to Disease; Hematologic Diseases; Intellectual Disability; Mutation; Neck; Phenotype; Siblings; Vestibular Diseases
PubMed: 38389298
DOI: 10.1002/ajmg.a.63567