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Seizure Mar 2024Wolf-Hirschhorn syndrome (WHS) is araredisorderwithan estimated prevalence being around 1 in 50,000 births. The syndrome is caused by the deletion of a critical region... (Review)
Review
Wolf-Hirschhorn syndrome (WHS) is araredisorderwithan estimated prevalence being around 1 in 50,000 births. The syndrome is caused by the deletion of a critical region (Wolf-Hirschhorn Syndrome Critical region- WHSCR) on chromosome 4p16.3. WHS is clinically characterized by pre-and postnatal growth restriction, hypotonia, intellectual disability, craniofacial dysmorphismand congenital fusion anomalies. The clinical aspects are variable due to the deletion size.Consistently, epilepsy is one of the major concerns for parents and professionals caring for children with WHS. Seizures tend to occur in over 90% of patients, with onset within the first 3 years of life, and a peak incidence at around 6-12 months of age. Approximately 20% of patients had the first seizure onset within the first 6 months of age, almost 50% at 6 to 12 months of age and about 25% later than 12 months of age. The main types of epileptic seizures occurring in patients with WHS were generalized tonic-clonic seizures (around 70%). These were followed by tonic spasms (20%); focal seizures with impaired awareness (12%) and clonicseizures in 7% of patients.Seizures are often triggered by fever, followed by infections of various systems. Particularly, half of WHS patients experience status epilepticus in the first years of life, which can be fatal. Due to limited number of reports on the topic of EEG abnormalities in epilepsy among WHS patients, it is difficult to determine whether there are any characteristic deviations for WHS. Although more than 300 persons with WHS have been reported in the literature, there is sparse knowledge about epilepsy and methods of its anti-seizure medication (ASM) management with an assessment of their effectiveness. The purpose of this systematic review is to briefly summarize achievements and advances in the field of epilepsy in Wolf-Hirschhorn syndrome.
Topics: Child; Humans; Infant; Wolf-Hirschhorn Syndrome; Epilepsy; Intellectual Disability; Status Epilepticus; Craniofacial Abnormalities; Chromosome Deletion; Phenotype
PubMed: 36526544
DOI: 10.1016/j.seizure.2022.12.001 -
Journal of Periodontology Mar 2020Orthodontic treatment can greatly impact the periodontium, especially in dentitions with a thin periodontal phenotype. Orthodontic tooth movement can result into...
BACKGROUND
Orthodontic treatment can greatly impact the periodontium, especially in dentitions with a thin periodontal phenotype. Orthodontic tooth movement can result into iatrogenic sequelae to these vulnerable anatomic conditions, such as development and exacerbation of bony dehiscence or fenestration defects, which can manifest loss of periodontal support and gingival recession (GR). This systematic review aimed to investigate whether periodontal phenotype modification therapy (PhMT) involving hard tissue augmentation (PhMT-b) or soft tissue augmentation (PhMT-s) has clinical benefits for patients undergoing orthodontic treatment.
METHODS
An electronic search was performed in two major databases for journals published in English language from January 1975 to January 2019 and a hand search of printed journals was also performed to identify human clinical trials reporting clinical and radiographic outcomes of patients receiving orthodontic treatment with or without hard and soft tissue augmentation procedures. Data were extracted and organized into tables for qualitative assessment.
RESULTS
Eight studies were identified evaluating the outcomes of PhMT in patients undergoing orthodontic therapy. Six studies evaluated patients receiving PhMT-b via corticotomy-assisted orthodontic therapy (CAOT) and simultaneous bone augmentation while the other two received PhMT-s before tooth movement. No studies investigated PhMT-b alone without CAOT and most studies focused on the mandibular anterior decompensation movements. There was high heterogeneity in the study design and inconsistency of the reported outcomes; therefore, a meta-analysis was not performed. Evidence at this moment supports CAOT with hard tissue augmentation accelerated tooth movement. However, only two studies provided direct comparison to support that CAOT with PhMT-b reduced the overall treatment time compared with conventional orthodontic treatment. No periodontal complications or evidence of severe root resorption were reported for both groups. Four studies provided radiographic assessment of the PhMT-b and demonstrated increased radiographic density or thicker facial bone after the treatment. Two studies reported an expanded tooth movement. One study reported an increase in keratinized tissue width post-CAOT plus PhMT-b, while another study with a 10-year follow-up showed a lower degree of relapse using the mandibular irregularity index when compared with conventional tooth movement alone. Two studies examined the effect of PhMT-s before orthodontic treatment. Unfortunately, no conclusions can be drawn because of the limited number of studies with contradicting outcomes.
CONCLUSIONS
Within the limited studies included in this systematic review, PhMT-b via particulate bone grafting together with CAOT may provide clinical benefits such as modifying periodontal phenotype, maintaining or enhancing facial bone thickness, accelerating tooth movement, expanding the scope of safe tooth movement for patients undergoing orthodontic tooth movement. The benefits of PhMT-s alone for orthodontic treatment remain undetermined due to limited studies available. However, PhMT-b appears promising and with many potential benefits for patients undergoing orthodontic tooth movement. There is a need for a higher quality of randomized controlled trials or case control studies with longer follow-up to investigate the effects of different grafting materials and surgical sites other than mandibular anterior region.
Topics: Bone Transplantation; Gingival Recession; Humans; Phenotype; Root Resorption; Tooth Movement Techniques; United States
PubMed: 31670836
DOI: 10.1002/JPER.19-0037 -
EBioMedicine Feb 2022Calcium plays a role in a wide range of biological functions. Here we conducted a phenome-wide Mendelian randomisation (MR-PheWAS) analysis and a systematic review for...
BACKGROUND
Calcium plays a role in a wide range of biological functions. Here we conducted a phenome-wide Mendelian randomisation (MR-PheWAS) analysis and a systematic review for MR studies to comprehensively investigate the health effects of serum calcium.
METHODS
One-hundred and thirty genetic variants strongly associated with serum calcium levels were used as instrumental variables. A phenome-wide association analysis (PheWAS) was conducted to examine the associations of genetically predicted serum calcium with 1473 distinct phenotypes in the UK Biobank including 339,197 individuals. Observed associations in PheWAS were further tested for replication in two-sample MR replication analysis. A systematic review for MR studies on serum calcium was performed to synthesize the published evidence and compare with the current MR-PheWAS findings.
FINDINGS
Higher genetically predicted calcium levels were associated with decreased risk of 5 diseases in dermatologic and musculoskeletal systems and increased risk of 17 diseases in circulatory, digestive, endocrine, genitourinary and immune systems. Eight associations were replicated in two-sample MR analysis. These included decreased risk of osteoarthritis and increased risk of coronary artery disease, myocardial infarction, coronary atherosclerosis, hyperparathyroidism, disorder of parathyroid gland, gout, and calculus of kidney and ureter with increased serum calcium. Systematic review of 25 MR studies provided supporting evidence on five out of the eight disease outcomes, while the increased risk of gout, hyperparathyroidism and disorder of parathyroid gland were novel findings.
INTERPRETATION
This study found wide-ranged health effects of high serum calcium, which suggests that the benefits and adversities of strategies promoting calcium intake should be assessed.
FUNDING
ET is supported by a CRUK Career Development Fellowship (C31250/A22804). XL is supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province. SCL acknowledges research funding from the Swedish Heart Lung Foundation (Hjärt-Lungfonden, 20210351), the Swedish Research Council (Vetenskapsrådet, 2019-00977), and the Swedish Cancer Society (Cancerfonden).
Topics: Calcium; Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Phenomics; Phenotype; Polymorphism, Single Nucleotide
PubMed: 35134646
DOI: 10.1016/j.ebiom.2022.103865 -
Human Reproduction Update Sep 2019A defining feature of sexual reproduction is the transmission of genomic information from both parents to the offspring. There is now compelling evidence that the...
BACKGROUND
A defining feature of sexual reproduction is the transmission of genomic information from both parents to the offspring. There is now compelling evidence that the inheritance of such genetic information is accompanied by additional epigenetic marks, or stable heritable information that is not accounted for by variations in DNA sequence. The reversible nature of epigenetic marks coupled with multiple rounds of epigenetic reprogramming that erase the majority of existing patterns have made the investigation of this phenomenon challenging. However, continual advances in molecular methods are allowing closer examination of the dynamic alterations to histone composition and DNA methylation patterns that accompany development and, in particular, how these modifications can occur in an individual's germline and be transmitted to the following generation. While the underlying mechanisms that permit this form of transgenerational inheritance remain unclear, it is increasingly apparent that a combination of genetic and epigenetic modifications plays major roles in determining the phenotypes of individuals and their offspring.
OBJECTIVE AND RATIONALE
Information pertaining to transgenerational inheritance was systematically reviewed focusing primarily on mammalian cells to the exclusion of inheritance in plants, due to inherent differences in the means by which information is transmitted between generations. The effects of environmental factors and biological processes on both epigenetic and genetic information were reviewed to determine their contribution to modulating inheritable phenotypes.
SEARCH METHODS
Articles indexed in PubMed were searched using keywords related to transgenerational inheritance, epigenetic modifications, paternal and maternal inheritable traits and environmental and biological factors influencing transgenerational modifications. We sought to clarify the role of epigenetic reprogramming events during the life cycle of mammals and provide a comprehensive review of how the genomic and epigenomic make-up of progenitors may determine the phenotype of its descendants.
OUTCOMES
We found strong evidence supporting the role of DNA methylation patterns, histone modifications and even non-protein-coding RNA in altering the epigenetic composition of individuals and producing stable epigenetic effects that were transmitted from parents to offspring, in both humans and rodent species. Multiple genomic domains and several histone modification sites were found to resist demethylation and endure genome-wide reprogramming events. Epigenetic modifications integrated into the genome of individuals were shown to modulate gene expression and activity at enhancer and promoter domains, while genetic mutations were shown to alter sequence availability for methylation and histone binding. Fundamentally, alterations to the nuclear composition of the germline in response to environmental factors, ageing, diet and toxicant exposure have the potential to become hereditably transmitted.
WIDER IMPLICATIONS
The environment influences the health and well-being of progeny by working through the germline to introduce spontaneous genetic mutations as well as a variety of epigenetic changes, including alterations in DNA methylation status and the post-translational modification of histones. In evolutionary terms, these changes create the phenotypic diversity that fuels the fires of natural selection. However, rather than being adaptive, such variation may also generate a plethora of pathological disease states ranging from dominant genetic disorders to neurological conditions, including spontaneous schizophrenia and autism.
Topics: Animals; Biological Evolution; DNA Methylation; Epigenesis, Genetic; Genome; Germ Cells; Heredity; Histone Code; Histones; Humans; Mammals; Mutation; Parents; Phenotype
PubMed: 31374565
DOI: 10.1093/humupd/dmz017 -
Clinical Reviews in Allergy & Immunology Dec 2020Activated phosphoinositide 3-kinase delta syndrome (APDS) is a novel primary immunodeficiency (PID) caused by heterozygous gain of function mutations in PI3Kδ catalytic... (Meta-Analysis)
Meta-Analysis
Activated phosphoinositide 3-kinase delta syndrome (APDS) is a novel primary immunodeficiency (PID) caused by heterozygous gain of function mutations in PI3Kδ catalytic p110δ (PIK3CD) or regulatory p85α (PIK3R1) subunits leading to APDS1 and APDS2, respectively. Patients with APDS present a spectrum of clinical manifestations, particularly recurrent respiratory infections and lymphoproliferation. We searched PubMed, Web of Science, and Scopus databases for APDS patients and screened for eligibility criteria. A total of 243 APDS patients were identified from 55 articles. For all patients, demographic, clinical, immunologic, and molecular data were collected. Overall, 179 APDS1 and 64 APDS2 patients were identified. The most common clinical manifestations were respiratory tract infections (pneumonia (43.6%), otitis media (28.8%), and sinusitis (25.9%)), lymphoproliferation (70.4%), autoimmunity (28%), enteropathy (26.7%), failure to thrive (20.6%), and malignancy (12.8%). The predominant immunologic phenotype was hyper-IgM syndrome (48.1%). Immunologic profiling showed decreased B cells in 74.8% and CD4 T cells in 64.8% of APDS patients. The c.3061 G>A (p. E1021K) mutation in APDS1 with 85% frequency and c.1425+1 G> (A, C, T) (p.434-475del) mutation in APDS2 with 79% frequency were hotspot mutations. The majority of APDS patients were placed on long-term immunoglobulin replacement therapy. Immunosuppressive agents such as rituximab, tacrolimus, rapamycin, and leniolisib were also administered for autoimmunity and inflammatory complications. In addition, hematopoietic stem cell transplantation (HSCT) was used in 12.8% of patients. APDS has heterogynous clinical manifestations. It should be suspected in patients with history of recurrent respiratory infections, lymphoproliferation, and raised IgM levels. Moreover, HSCT should be considered in patients with severe and complicated clinical manifestations with no or insufficient response to the conventional therapies.
Topics: Adolescent; Adult; Autoimmunity; Biomarkers; Child; Class I Phosphatidylinositol 3-Kinases; Disease Susceptibility; Female; Gain of Function Mutation; Genetic Predisposition to Disease; Humans; Male; Phenotype; Primary Immunodeficiency Diseases; Young Adult
PubMed: 31111319
DOI: 10.1007/s12016-019-08738-9 -
International Orthodontics Dec 2023The aim of this systematic review (Prospero CRD42022323188) is to investigate whether an association exists in patients with amelogenesis imperfecta (AI) between...
INTRODUCTION
The aim of this systematic review (Prospero CRD42022323188) is to investigate whether an association exists in patients with amelogenesis imperfecta (AI) between occlusal characteristics and genotype on the one hand and enamel structural phenotype on the other.
MATERIAL AND METHODS
Reports up to May 2023 assessing occlusion of individuals with AI were browsed in a systematic search using Medline, Embase, ISI Web of Science, and the grey literature. Randomised control trials, case control studies, and case series specifying both occlusion, assessed by cephalometric or clinical analysis, and genotype or dental phenotype in patients with AI were included without any age limitation. Two authors independently selected the publications and extracted the data in accordance with the PRISMA statement. The risk of bias was assessed with the Critical Appraisal Checklists from the Johanna Briggs Institute.
RESULTS
Twenty-five articles were chosen from the 261 results. Most of the included publications were case series (n=22) and case control studies (n=3). Thirteen studies reported both a genotype (ENAM, FAM83H, FAM20A, DLX3, CNMM4, WDR72) and occlusal diagnostic. The methodological quality of the studies was moderate. All AI phenotypes showed an open bite (OB) rate around 35%, except mixed form. The other malocclusions were not often mentioned. No correlation between occlusal phenotype and genotype or AI phenotype could be identified in patients with AI, as most studies had short occlusal descriptions and small sample sizes.
CONCLUSION
OB malocclusions were more frequently reported in AI. This review highlighted the need for a more accurate description of orofacial features associated with AI, to better clarify the role of amelogenesis genes in the regulation of craniofacial morphogenesis and identify patients requiring orthognathic surgery at an early stage.
Topics: Humans; Amelogenesis Imperfecta; Genotype; Phenotype; Dental Enamel; Malocclusion; Open Bite; Proteins
PubMed: 37494776
DOI: 10.1016/j.ortho.2023.100789 -
Movement Disorders : Official Journal... Feb 2022Pathogenic variants in 5 genes (GCH1, TH, PTS, SPR, and QDPR), involved in dopamine/tetrahydrobiopterin biosynthesis or recycling, have been linked to Dopa-responsive... (Review)
Review
BACKGROUND
Pathogenic variants in 5 genes (GCH1, TH, PTS, SPR, and QDPR), involved in dopamine/tetrahydrobiopterin biosynthesis or recycling, have been linked to Dopa-responsive dystonia (DRD). Diagnosis and treatment are often delayed due to high between- and within-group variability.
OBJECTIVES
Comprehensively analyzed individual genotype, phenotype, treatment response, and biochemistry information.
METHODS
734 DRD patients and 151 asymptomatic GCH1 mutation carriers were included using an MDSGene systematic literature review and an automated classification approach to distinguish between different forms of monogenic DRDs.
RESULTS
Whereas dystonia, L-Dopa responsiveness, early age at onset, and diurnal fluctuations were identified as red flags, parkinsonism without dystonia was rarely reported (11%) and combined with dystonia in only 18% of patients. While sex was equally distributed in autosomal recessive DRD, there was female predominance in autosomal dominant DYT/PARK-GCH1 patients accompanied by a lower median age at onset and more dystonia in females compared to males. Accordingly, the majority of asymptomatic heterozygous GCH1 mutation carriers (>8 years of age) were males. Multiple other subgroup-specific characteristics were identified, showing high accuracy in the automated classification approach: Seizures and microcephaly were mostly seen in DYT/PARK-PTS, autonomic symptoms appeared commonly in DYT/PARK-TH and DYT/PARK-PTS, and sleep disorders and oculogyric crises in DYT/PARK-SPR. Biochemically, homovanillic acid and 5-hydroxyindoleacetic acid in CSF were reduced in most DRDs, but neopterin and biopterin were increased only in DYT/PARK-PTS and DYT/PARK-SPR. Hyperphenylalaninemia was seen in DYT/PARK-PTS, DYT/PARK-QDPR, and rarely reported in autosomal recessive DYT/PARK-GCH1.
CONCLUSIONS
Our indicators will help to specify diagnosis and accelerate start of treatment. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Dystonia; Dystonic Disorders; Female; GTP Cyclohydrolase; Genotype; Humans; Male; Phenotype
PubMed: 34908184
DOI: 10.1002/mds.28874 -
International Journal of Infectious... Nov 2022A systematic literature review was conducted to assess the epidemiology and economic burden of dengue in Malaysia. (Review)
Review
OBJECTIVES
A systematic literature review was conducted to assess the epidemiology and economic burden of dengue in Malaysia.
METHODS
Embase, MEDLINE, Evidence-Based Reviews databases, and gray literature sources were searched for English and Malay studies and surveillance reports on the epidemiology (between 2012 and 2019) and costs (between 2009 and 2019) of dengue in Malaysia. Independent screening of titles/abstracts, followed by full texts was performed using prespecified criteria.
RESULTS
A total of 198 publications were included (55 peer-reviewed and 143 gray literature). Dengue incidence has been increasing in recent years, with 130,101 cases (dengue fever 129,578 cases; dengue hemorrhagic fever 523 cases) reported in 2019, which is the highest since 2012. All dengue virus serotypes co-circulated between 2004 and 2017, and major outbreaks occurred in a cyclical pattern, often associated with a change in the predominant circulating serotype. Economic impacts are substantial, including the societal impact of lost work (7.2-8.8 days) and school days (3.2-4.1 days) due to dengue.
CONCLUSION
The rising incidence and high cost of dengue, coupled with overlapping diseases, will likely result in further pressures on the healthcare system. To appropriately mitigate and control dengue, it is critical to implement integrated strategies, including vaccination, to reduce the burden of dengue.
Topics: Humans; Dengue; Malaysia; Serogroup; Disease Outbreaks; Incidence
PubMed: 36089149
DOI: 10.1016/j.ijid.2022.09.006 -
Clinical Oral Implants Research Sep 2023To assess the correlation between the periodontal phenotype (PP) and sinus membrane thickness (SMT) in humans. (Review)
Review
AIM
To assess the correlation between the periodontal phenotype (PP) and sinus membrane thickness (SMT) in humans.
METHODS
This review was conducted according to the PRISMA guidelines. Two reviewers independently carried out electronic and manual literature searches of studies published in English, German, and Spanish, from 1970 to September 2022 in four electronic databases, PubMed/Medline, Scopus, Cochrane Library, and Web of Science, in addition to gray literature. Studies that assessed the correlation between PP and SMT in adults (aged 18 years) were included. Methodological quality was evaluated using the Appraisal Tool for Cross-Sectional Studies (AXIS) for articles that met the eligibility criteria.
RESULTS
Six studies, including 510 patients, were considered for qualitative analysis. All included studies were cross-sectional, and the correlation between the PP and SMT was evaluated, finding a positive and high correlation in 83.3% of them, based on a value of ≥0.7. All the included studies were assessed with a high overall risk of bias.
CONCLUSIONS
Periodontal phenotype and sinus membrane thickness are likely correlated. Nevertheless, further standardized studies are required to draw definitive conclusions.
Topics: Adult; Humans; Membranes; Phenotype
PubMed: 37427881
DOI: 10.1111/clr.14121 -
Minerva Medica Oct 2021Asthma is a complex disorder characterized by expiratory airflow limitation, wheeze, shortness of breath, chest tightness and cough, which can vary over time and in...
INTRODUCTION
Asthma is a complex disorder characterized by expiratory airflow limitation, wheeze, shortness of breath, chest tightness and cough, which can vary over time and in intensity. Being highly heterogeneous, asthma was characterized and classified in several asthma phenotypes and endotypes from 1947 until today. The present systematic review aims to summarize and describe evidence that was published in the last ten years in the field of asthma phenotyping and endotyping.
EVIDENCE ACQUISITION
The systematic review resumed high-quality evidence (clinical trials and randomized control trials) retrieved on MEDLINE and EMBASE databanks and involving adult asthmatic populations. Analyses of literature were conducted according to PRISMA and CASP guidelines.
EVIDENCE SYNTHESIS
Querying MEDLINE and EMBASE databanks, 5019 and 12261 entries were retrieved, respectively. Applying limitations for year of publication, age of participants, and type of publication, the search results were reduced to 98 and 132 articles, respectively. After data abstraction and resolution of duplications, only 50 articles were further evaluated. The research products were then classified first in macro-areas of interest (phenotypes or endotypes) and then in detailed micro-areas.
CONCLUSIONS
This systematic review overviews the principal findings available from high-quality literature in the last decade concerning asthma phenotypes and endotypes. Asthma has been described from different points of view, characterizing symptoms, microbiota composition, comorbidities, viral infections, and airway and/or systemic inflammatory status. The comprehension of precise mechanisms underlying asthma pathogenesis is thereby the basis for the development of novel therapeutic strategies, likely essential to the development of precision medicine.
Topics: Adult; Age Factors; Asthma; Biological Products; Clinical Trials as Topic; Comorbidity; Cough; Disease Progression; Drug Resistance; Humans; Microbiota; Obesity; Phenotype; Randomized Controlled Trials as Topic; Respiratory Sounds; Sputum; Steroids; Treatment Outcome
PubMed: 33969960
DOI: 10.23736/S0026-4806.21.07498-X