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Journal of Clinical Medicine Jun 2024Floating-Harbor syndrome (FHS) is an extremely rare genetic disorder connected with a distinctive facial appearance, various skeletal malformations, delayed bone age,...
Floating-Harbor syndrome (FHS) is an extremely rare genetic disorder connected with a distinctive facial appearance, various skeletal malformations, delayed bone age, and expressive language delays. It is caused by heterozygous mutations in the Snf2-related CREBBP activator protein (SRCAP) gene. The aim of this paper is to describe the case of a 14-year-old male with FHS, referring to a review of the literature, and to collect all reported symptoms. In addition, the orthodontic treatment of the patient is described. For this, the electronic databases PubMed and Scopus were searched using the keyword "Floating-Harbor syndrome". Similar to previous cases in the literature, the patient presented with short stature; a triangular face with a large bulbous nose; deep-set eyes and narrow eyelid gaps; a wide mouth with a thin vermilion border of the upper lip; and dorsally rotated, small ears. They also presented some less-described symptoms, such as macrodontia and micrognathia. Moreover, mild mental retardation, microcephaly, and delayed psychomotor development were found. On the basis of an extraoral, intraoral examination, X-rays, and CBCT, he was diagnosed with overbite, canine class I and angle class III, on both sides. To the best of our knowledge, orthodontic treatment of this disease has not been assessed in detail so far, so this is the first case.
PubMed: 38929963
DOI: 10.3390/jcm13123435 -
Frontiers in Oncology 2024Newly identified as a radiological concept, interstitial lung abnormalities (ILA) is emerging as a prognostic factor for lung cancer. Yet, debates persist regarding the...
BACKGROUND
Newly identified as a radiological concept, interstitial lung abnormalities (ILA) is emerging as a prognostic factor for lung cancer. Yet, debates persist regarding the prognostic significance of ILA in lung cancer. Our inaugural meta-analysis aimed to investigate the correlation between ILA and lung cancer outcomes, offering additional insights for clinicians in predicting patient prognosis.
METHODS
Articles meeting the criteria were found through PubMed, the Cochrane Library, EMBASE, and Web of Science by February 29, 2024. The outcomes evaluated were the survival rates such as overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and cancer-specific survival (CSS).
RESULTS
A total of 12 articles with 4416 patients were included in this meta-analysis. The pooled results showed that lung cancer patients with interstitial lung abnormalities had an inferior OS (n=11; HR=2.22; 95% CI=1.68-2.95; P<0.001; I = 72.0%; Ph<0.001), PFS (n=3; HR=1.59; 95% CI=1.08-2.32; P=0.017; I = 0%; Ph=0.772), and CSS (n=2; HR=4.00; 95% CI=1.94-8.25; P<0.001; I = 0%; Ph=0.594) than those without, however, the ILA was not significantly associated with the DFS (n=2; HR=2.07; 95% CI=0.94-7.02; P=0.066; I = 90.4%; Ph=0.001). Moreover, lung cancer patients with ILA were significantly correlated with male (OR=2.43; 95% CI=1.48-3.98; P<0.001), smoking history (OR=2.11; 95% CI=1.37-3.25; P<0.001), advanced age (OR=2.50; 95% CI=1.56-4.03; P<0.001), squamous carcinoma (OR=0.42; 95% CI=0.24-0.71; P=0.01), and EGFR mutation (OR=0.50; 95% CI=0.32-0.78; P=0.002). The correlation between ILA and race, stage, ALK, however, was not significant.
CONCLUSION
ILA was a availability factors of prognosis in patients with lung cancers. These findings highlight the importance of early pulmonary fibrosis, namely ILA for prognosis in patients with lung cancer, and provide a partial rationale for future clinical work.
PubMed: 38800393
DOI: 10.3389/fonc.2024.1397246 -
Children (Basel, Switzerland) Apr 2024CACNA1C gene encodes the alpha 1 subunit of the CaV1.2 L-type Ca2+ channel. Pathogenic variants in this gene have been associated with cardiac rhythm disorders such as... (Review)
Review
CACNA1C gene encodes the alpha 1 subunit of the CaV1.2 L-type Ca2+ channel. Pathogenic variants in this gene have been associated with cardiac rhythm disorders such as long QT syndrome, Brugada syndrome and Timothy syndrome. Recent evidence has suggested the possible association between CACNA1C mutations and neurologically-isolated (in absence of cardiac involvement) phenotypes in children, giving birth to a wider spectrum of CACNA1C-related clinical presentations. However, to date, little is known about the variety of both neurological and non-neurological signs/symptoms in the neurologically-predominant phenotypes. We conducted a systematic review of neurologically-predominant presentations without cardiac conduction defects, associated with CACNA1C mutations. We also reported a novel de novo missense pathogenic variant in the CACNA1C gene of a children patient presenting with constructional, dressing and oro-buccal apraxia associated with behavioral abnormalities, mild intellectual disability, dental anomalies, gingival hyperplasia and mild musculoskeletal defects, without cardiac conduction defects. The present study highlights the importance of considering the investigation of the CACNA1C gene in children's neurological isolated syndromes, and expands the phenotype of the CACNA1C related conditions. In addition, the present study highlights that, even in absence of cardiac conduction defects, nuanced clinical manifestations of the Timothy syndrome (e.g., dental and gingival defects) could be found. These findings suggest the high variable expressivity of the CACNA1C gene and remark that the absence of cardiac involvement should not mislead the diagnosis of a CACNA1C related disorder.
PubMed: 38790536
DOI: 10.3390/children11050541 -
Oral Diseases May 2024Targeted therapy has the potential to be used in the neoadjuvant setting for odontogenic tumors, reducing the morbidities associated with major surgery. In this regard,... (Review)
Review
Targeted therapy has the potential to be used in the neoadjuvant setting for odontogenic tumors, reducing the morbidities associated with major surgery. In this regard, the aim of this study was to summarize the current evidence on the different forms of targeted therapy, effectiveness, and drawbacks of this course of treatment. Four databases were searched electronically without regard to publication date or language. Grey literature searches and manual searches were also undertaken. Publications with sufficient clinical data on targeted therapy for odontogenic tumors were required to meet the criteria for eligibility. The analysis of the data was descriptive. A total of 15 papers comprising 17 cases (15 ameloblastomas and 2 ameloblastic carcinomas) were included. Numerous mutations were found, with BRAF V600E being most common. Dabrafenib was the most utilized drug in targeted therapy. Except for one case, the treatment reduced the size of the lesion (16/17 cases), showing promise. Most of the adverse events recorded were mild, such as skin issues, voice changes, abnormal hair texture, dry eyes, and systemic symptoms (e.g., fatigue, joint pain, and nausea). It is possible to reach the conclusion that targeted therapy for ameloblastoma and ameloblastic carcinoma may be a useful treatment strategy, based on the findings of the included studies.
PubMed: 38693620
DOI: 10.1111/odi.14962 -
Epilepsy & Behavior : E&B Jun 2024To estimate the prevalence of epilepsy and febrile seizures and their association with genotype, i.e., 15q11-q13 deletions, uniparental chromosome 15 disomy (UPD) and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To estimate the prevalence of epilepsy and febrile seizures and their association with genotype, i.e., 15q11-q13 deletions, uniparental chromosome 15 disomy (UPD) and other mutations, in the population with Prader-Willi syndrome (PWS).
METHODS
A systematic search of Medline, Scopus, Web of Science and the Cochrane Library was conducted. Studies estimating the prevalence of seizures, epilepsy and febrile seizures in the PWS population were included. Meta-analyses of the prevalence of epilepsy and febrile seizures and their association with genotype using the prevalence ratio (PR) were performed.
RESULTS
Fifteen studies were included. The prevalence of epilepsy was 0.11 (0.07, 0.15), similar to the prevalence of febrile seizures, with a prevalence of 0.09 (0.05, 0.13). The comparison "deletion vs. UPD" had a PR of 2.03 (0.90, 4.57) and 3.76 (1.54, 9.18) for epilepsy and febrile seizures.
CONCLUSIONS
The prevalence of seizure disorders in PWS is higher than in the general population. In addition, deletions in 15q11-q13 may be associated with a higher risk of seizure disorders. Therefore, active screening for seizure disorders in PWS should improve the lives of these people. In addition, genotype could be used to stratify risk, even for epilepsy, although more studies or larger sample sizes are needed.
Topics: Humans; Prader-Willi Syndrome; Epilepsy; Prevalence; Genotype; Chromosomes, Human, Pair 15
PubMed: 38663143
DOI: 10.1016/j.yebeh.2024.109803 -
PloS One 2024Echogenic Intracardiac Foci (EIF) are non-structural markers identified during the routine 18-20-week foetal anomaly ultrasound scan yet their clinical significance on...
BACKGROUND
Echogenic Intracardiac Foci (EIF) are non-structural markers identified during the routine 18-20-week foetal anomaly ultrasound scan yet their clinical significance on future outcomes for the infant is unclear.
OBJECTIVE
To examine the association between EIF and risk of preterm birth, chromosomal abnormalities, and cardiac abnormalities.
DESIGN
A review across four databases to identify English language journal articles of EIF using a cohort study design. All studies were reviewed for quality using the Critical Appraisal Skills Programme (CASP) checklist and data extracted for comparison and analysis.
RESULTS
19 papers from 9 different countries were included. Combining these studies showed 4.6% (95% CI = 4.55-4.65%) of all pregnancies had EIF which was on the left in 86% of cases, on the right in 3% of cases and bilaterally in 10%. There was no evidence that EIF was associated with higher rates of preterm birth. However, it is possible that infants with EIF were more likely to be terminated rather than be born preterm as there was a 2.1% (range 0.3-4.2%) rate of termination or death of the foetus after week 20 among those with EIF. There was no evidence that EIF alone is highly predictive of chromosomal abnormalities. There was evidence that EIF is associated with higher rates of minor cardiac abnormalities (e.g. ventricular septal defect, tricuspid regurgitation or mitral regurgitation)) with 5.1% (224 of 4385) of those with EIF showing cardiac abnormalities (3.08% in retrospective studies and 17.85% in prospective studies). However, the risk of cardiac defects was only higher with right-sided EIF and where the EIF persisted into the third trimester. However, this is a rare event and would be seen in an estimated 4 per 10,000 pregnancies.
CONCLUSION
EIF alone was not associated with adverse outcomes for the infant. Only persistent EIF on the right side showed evidence of carrying a higher risk of cardiac abnormality and would warrant further follow-up.
Topics: Female; Humans; Pregnancy; Chromosome Aberrations; Heart Defects, Congenital; Pregnancy Outcome; Pregnancy Trimester, Second; Premature Birth; Ultrasonography, Prenatal
PubMed: 38648215
DOI: 10.1371/journal.pone.0298365 -
BMC Oral Health Apr 2024Oral health impacts systemic health, individual well-being, and quality of life. It is important to identify conditions that may exacerbate oral disease to aid public...
BACKGROUND
Oral health impacts systemic health, individual well-being, and quality of life. It is important to identify conditions that may exacerbate oral disease to aid public health and policy development and promote targeted patient treatment strategies. Developmental defects can increase an individual's risk of dental caries, hypersensitivity, premature tooth wear, erosion, and poor aesthetics. As part of an ongoing study assessing oral health in adults with cystic fibrosis at Cork University Dental School and Hospital, a systematic review of available literature was conducted to assess the prevalence of enamel defects in people with cystic fibrosis.
AIMS
To critically evaluate the literature to determine if the prevalence of developmental defects of enamel is higher in people with cystic fibrosis (PwCF).
METHODS
Data Sources: Three online databases were searched Embase, Scopus, and Web of Science Core Collection. Studies that examined an association between cystic fibrosis and developmental defects of enamel were included in this systematic review.
RESULTS
The initial search identified 116 publications from the following databases Embase, Web of Science Core Collection, and Scopus. Eleven studies were included for qualitative analysis. Nine studies concluded that PwCF had a higher prevalence of enamel defects than control people and one study found no difference in cystic fibrosis (CF) status. All studies had a risk of bias that may influence study results and their interpretation.
CONCLUSIONS
The results of the systematic review show a consistent pattern that PwCF have a higher prevalence of DDE than people without CF. Genetic dysfunction, chronic systemic infections, and long-term antibiotic use are possible aetiological causes. This review highlights the need for future studies to investigate if DDEs are caused by the underlying CFTR mutation or as a consequence of disease manifestations and/or management.
Topics: Adult; Humans; Prevalence; Cystic Fibrosis; Dental Caries; Quality of Life; Dental Enamel; Developmental Defects of Enamel
PubMed: 38609911
DOI: 10.1186/s12903-024-04227-4 -
Acta Neurologica Belgica Apr 2024BRAT1 (BRCA1-associated ataxia telangiectasia mutated activator 1) is involved in many important biological processes, including DNA damage response and maintenance of...
BACKGROUND
BRAT1 (BRCA1-associated ataxia telangiectasia mutated activator 1) is involved in many important biological processes, including DNA damage response and maintenance of mitochondrial homeostasis. Dysfunctional BRAT1 causes variable clinical phenotypes, which hinders BRAT1-related disease from recognition and diagnosis.
METHODS
Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was the guideline for this systematic review. MEDLINE was searched by terms ("BAAT1" and "BRAT1") from inception until June 21, 2022.
RESULTS
Twenty-eight studies, screened out of 49 records, were included for data extraction. The data from fifty patients with mutated BRAT1 were collected. There are 3 high relevant phenotypes, 4 medium relevant phenotypes and 3 low relevant phenotypes. Eye-related abnormal features were most frequently reported: 27 abnormal features were observed. Thirty-nine kinds of pathogenic nucleotide change in BRAT1 were reported. Top three common mutations of BRAT1 were c.638_639insA (16 cases), c.1395G > A (5 cases) and c.294dupA (4 cases). Homozygous mutations in BRAT1 presented a more severe phenotype than those who are compound heterozygotes.
CONCLUSIONS
This is the first comprehensive systematic review to present quantitative data about clinical characteristics of BRAT1-related disease, which helps doctors to recognize and diagnose it easier.
PubMed: 38607605
DOI: 10.1007/s13760-024-02507-y -
Clinical & Translational Oncology :... Jul 2024Molecular classification of endometrial cancer (EC) has become a promising information to tailor preoperatively the surgical treatment. We aimed to evaluate the rate of... (Meta-Analysis)
Meta-Analysis
PURPOSE
Molecular classification of endometrial cancer (EC) has become a promising information to tailor preoperatively the surgical treatment. We aimed to evaluate the rate of lymph node metastases (LNM) in patients with EC according to molecular profile.
METHODS
A systematic review and meta-analysis were performed according to PRISMA guidelines by searching in two major electronic databases (PubMed and Scopus), including original articles reporting lymph node metastases according to the molecular classification of EC as categorized in the ESGO-ESMO-ESP guidelines.
RESULTS
Fifteen studies enrolling 3056 patients were included. Pooled prevalence LNM when considering only patients undergoing lymph node assessment was 4% for POLE-mutated (95%CI: 0-12%), 22% for no specific molecular profile (95% CI: 9-39%), 23% for Mismatch repair-deficiency (95%CI: 10-40%) and 31% for p53-abnormal (95%CI: 24-39%).
CONCLUSIONS
The presence of LNM seems to be influenced by molecular classification. P53-abnormal group presents the highest rate of nodal involvement, and POLE-mutated the lowest.
Topics: Humans; Endometrial Neoplasms; Female; Lymphatic Metastasis; Tumor Suppressor Protein p53; Mutation; Poly-ADP-Ribose Binding Proteins; DNA Polymerase II; Lymph Nodes; Biomarkers, Tumor
PubMed: 38578538
DOI: 10.1007/s12094-024-03401-y -
Journal of Human Genetics Jul 2024Spondylocostal dysostosis (SCDO) encompasses a group of skeletal disorders characterized by multiple segmentation defects in the vertebrae and ribs. SCDO has a complex...
Spondylocostal dysostosis (SCDO) encompasses a group of skeletal disorders characterized by multiple segmentation defects in the vertebrae and ribs. SCDO has a complex genetic etiology. This study aimed to analyze and identify pathogenic variants in a fetus with SCDO. Copy number variant sequencing and whole exome sequencing were performed on a Chinese fetus with SCDO, followed by bioinformatics analyses, in vitro functional assays and a systematic review on the reported SCDO cases with LFNG pathogenic variants. Ultrasound examinations in utero exhibited that the fetus had vertebral malformation, scoliosis and tethered cord, but rib malformation was not evident. We found a novel homozygous variant (c.1078 C > T, p.R360C) within the last exon of LFNG. The variant was predicted to cause loss of function of LFNG by in silico prediction tools, which was confirmed by an in vitro assay of LFNG enzyme activity. The systematic review listed a total of 20 variants of LFNG in SCDO. The mutational spectrum spans across all exons of LFNG except the last one. This study reported the first Chinese case of LFNG-related SCDO, revealing the prenatal phenotypes and expanding the mutational spectrum of the disorder.
Topics: Humans; Female; Exome Sequencing; Fetus; Pregnancy; Abnormalities, Multiple; Mutation; Meningomyelocele; DNA Copy Number Variations; Asian People; East Asian People; Hernia, Diaphragmatic
PubMed: 38565611
DOI: 10.1038/s10038-024-01248-3