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Imaging Science in Dentistry Mar 2024Pycnodysostosis (PYCD), an autosomal recessive syndrome, is characterized by an imbalance in bone remodeling that produces various clinical and radiographic craniofacial... (Review)
Review
PURPOSE
Pycnodysostosis (PYCD), an autosomal recessive syndrome, is characterized by an imbalance in bone remodeling that produces various clinical and radiographic craniofacial manifestations. This review represents a systematic examination of these manifestations, as well as oral features associated with PYCD.
MATERIALS AND METHODS
A systematic review was conducted across 8 databases from February to March 2023. The search strategy focused on studies reporting cases of PYCD that examined the clinical and radiographic craniofacial and oral characteristics associated with this syndrome.
RESULTS
The review included 84 studies, encompassing a total of 179 cases of PYCD. More than half of the patients were female (55.3%), and the mean age was 14.7 years. Parental consanguinity was reported in 51.4% of the cases. The most common craniofacial clinical manifestation was a prominent nose, observed in 57.5% of cases. Radiographically, the most frequently reported craniofacial characteristics included the presence of an obtuse mandibular angle (84.3%) and frontal cranial bosses (82.1%). Clinical and radiographic examinations revealed oral alterations, with micrognathia present in 62.6% of patients and malocclusion in 59.2%. Among dental anomalies, tooth agenesis was the most commonly reported, affecting 15.6% of patients.
CONCLUSION
Understanding the clinical and radiographic craniofacial features of PYCD is crucial for dental professionals. This knowledge enables these clinicians to devise effective treatment plans and improve patient quality of life.
PubMed: 38571780
DOI: 10.5624/isd.20230191 -
The British Journal of Dermatology Apr 2016Buschke-Ollendorff syndrome (BOS) is a rare, often benign, autosomal skin disorder. BOS commonly presents with nontender connective tissue naevi and sclerotic bony... (Review)
Review
Buschke-Ollendorff syndrome (BOS) is a rare, often benign, autosomal skin disorder. BOS commonly presents with nontender connective tissue naevi and sclerotic bony lesions (osteopoikilosis [OPK]). Herein, we summarize the presenting features of BOS and potential associations by conducting a systematic review of the literature and summarizing a cohort seen at the Hospital for Sick Children (HSC), Toronto, Canada. PubMed was searched using the following terms: 'BOS'; 'dermatofibrosis lenticularis'; 'OPK'; 'LEMD3'; 'elastoma'; 'collagenoma'. Only case reports were included, without date or language restrictions. Cases were further narrowed to those where patients or their families had a combination of skin and bony lesions, or a positive genetic test. Data were summarized using frequencies. In total, 594 reports were discovered, of which 546 (92%) were excluded. The remaining 48 accounted for 164 cases. Skin lesions were noted in 24% of cases and bony lesions in 20%, while 54% of patients had both. In 1% of cases the diagnosis was made on genetic testing alone. A family history was noted in 92% of cases. All patients with spinal stenosis (2%) or shortened status (7%) had OPK. Six per cent of patients had neurological problems. However, 50% of the cohort from HSC had cognitive delays, and only cases from 2007 onwards reported cognitive delays (the prevalence was 17% among those cases). This review confirms the classical diagnostic features of BOS. In addition, it highlights a previously unreported association between a shortened stature and OPK, as well as a possible association with cognitive delays.
Topics: Adolescent; Adult; Age Distribution; Age of Onset; Aged; Child; Female; Humans; Male; Middle Aged; Osteopoikilosis; Skin Diseases, Genetic; Young Adult
PubMed: 26708699
DOI: 10.1111/bjd.14366 -
The Cochrane Database of Systematic... Oct 2014Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second... (Review)
Review
BACKGROUND
Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal hemoglobin polymerisation leading to a symptomatic disorder.Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene.
OBJECTIVES
The objectives of this review are:- to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease;- to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 21 July 2014.
SELECTION CRITERIA
All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting.
DATA COLLECTION AND ANALYSIS
No trials of gene therapy for sickle cell disease were found.
MAIN RESULTS
No trials of gene therapy for sickle cell disease were reported.
AUTHORS' CONCLUSIONS
No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.
Topics: Anemia, Sickle Cell; Genetic Therapy; Humans
PubMed: 25300171
DOI: 10.1002/14651858.CD007652.pub4 -
Journal of Neurology Jun 2022Adult polyglucosan body disease (APBD) is a rare but probably underdiagnosed autosomal recessive neurodegenerative disorder due to pathogenic variants in GBE1. The... (Review)
Review
Adult polyglucosan body disease (APBD) is a rare but probably underdiagnosed autosomal recessive neurodegenerative disorder due to pathogenic variants in GBE1. The phenotype is characterized by neurogenic bladder dysfunction, spastic paraplegia, and axonal neuropathy. Additionally, cognitive symptoms and dementia have been reported in APBD but have not been studied systematically. Using exome sequencing, we identified two previously unreported bi-allelic missense GBE1 variants in a patient with severe memory impairment along with the typical non-cognitive symptoms. We were able to confirm a reduction of GBE1 activity in blood lymphocytes. To characterize the neuropsychological profile of patients suffering from APBD, we conducted a systematic review of cognitive impairment in this rare disease. Analysis of 24 cases and case series (in total 58 patients) showed that executive deficits and memory impairment are the most common cognitive symptoms in APBD.
Topics: Cognitive Dysfunction; Glycogen Storage Disease; Humans; Mutation, Missense; Nervous System Diseases
PubMed: 34999962
DOI: 10.1007/s00415-022-10960-z -
Neurotoxicology Jul 2017Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by chorea, behavioural and psychiatric manifestations, and dementia, caused... (Review)
Review
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by chorea, behavioural and psychiatric manifestations, and dementia, caused by a CAG triplet repeat expansion in the huntingtin gene. Systematic review of the literature was conducted to determine the risk factors for the onset and progression of HD. Multiple databases were searched, using terms specific to Huntington disease and to studies of aetiology, risk, prevention and genetics, limited to studies on human subjects published in English or French between 1950 and 2010. Two reviewers independently screened the abstracts and identified potentially relevant articles for full-text review using predetermined inclusion criteria. Three major categories of risk factors for onset of HD were identified: CAG repeat length in the huntingtin gene, CAG instability, and genetic modifiers. Of these, CAG repeat length in the huntingtin gene is the most important risk factor. For the progression of HD: genetic, demographic, past medical/clinical and environmental risk factors have been studied. Of these factors, genetic factors appear to play the most important role in the progression of HD. Among the potential risk factors, CAG repeat length in the mutant allele was found to be a relatively consistent and significant risk factor for the progression of HD, especially in motor, cognitive, and other neurological symptom deterioration. In addition, there were many consistent results in the literature indicating that a higher number of CAG repeats was associated with shorter survival, faster institutionalization, and earlier percutaneous endoscopic gastrostomy.
Topics: Disease Progression; Humans; Huntingtin Protein; Huntington Disease; Risk Factors; Trinucleotide Repeats
PubMed: 28111121
DOI: 10.1016/j.neuro.2017.01.005 -
The Cochrane Database of Systematic... Aug 2021Cystic fibrosis (CF) is an autosomal recessive, life-limiting, multisystem disease affecting over 70,000 individuals worldwide. Between 80% and 90% of people with CF... (Review)
Review
BACKGROUND
Cystic fibrosis (CF) is an autosomal recessive, life-limiting, multisystem disease affecting over 70,000 individuals worldwide. Between 80% and 90% of people with CF suffer with pancreatic exocrine insufficiency, which if left untreated, leads to a poor nutritional status. Pancreatic enzyme replacement therapy (PERT) has been shown to be effective in improving nutritional status and subsequently associated with improved lung function. However, the timings of PERT administration in relation to a meal are subjective and not standardised, meaning that variations in the timing of PERT dosing persist.
OBJECTIVES
The primary objective of the review is to compare the efficacy (fat absorption) and effectiveness (nutritional status, lung function and quality of life) of different PERT dosing strategies in terms of timing of administration for treating dietary malabsorption in all individuals with CF.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Date of last search: 24 June 2021. We also searched ongoing trials registers on 09 July 2021.
SELECTION CRITERIA
Randomised controlled trials (RCTs), including cross-over RCTs with a minimum washout period of two weeks, and quasi-RCTs of PERT dosing regimens in people (of any age) with CF.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed and screened the studies identified from the searches. We planned to use GRADE to assess the certainty of evidence for our pre-specified critical outcomes, but we did not identify any eligible studies.
MAIN RESULTS
No studies met the eligibility criteria and therefore we did not include any in this review. The excluded studies were either cross-over in design (but lacking a sufficient washout period between treatments) or did not assess the timing of PERT. One study which was terminated early is awaiting assessment pending further information.
AUTHORS' CONCLUSIONS
We were unable to determine whether one dosing schedule for PERT is better than another since we identified no eligible RCTs. While the introduction of PERT to people with CF can improve their nutritional status, there are a limited number of studies which address this review question, and none met our eligibility criteria. Since malnutrition and adverse gastrointestinal symptoms remain a common feature in CF, the assessment of the relative performance of dosing schedules may provide evidence to improve outcomes in people with CF who are pancreatic insufficient. Further research is needed to fully evaluate the role of dosing schedules for PERT in fat absorption. Research should also establish reliable outcome measures and minimal clinically important differences. While RCTs with a cross-over design may have advantages over a parallel group design, an adequate washout period between intervention periods is essential.
Topics: Cystic Fibrosis; Enzyme Replacement Therapy; Humans; Nutritional Status; Pancreas
PubMed: 34339047
DOI: 10.1002/14651858.CD013488.pub2 -
International Journal of Molecular... Jan 2023PURA-related neurodevelopmental disorders (PURA-NDDs) are a rare genetic disease caused by pathogenic autosomal dominant variants in the PURA gene or a deletion... (Review)
Review
PURA-related neurodevelopmental disorders (PURA-NDDs) are a rare genetic disease caused by pathogenic autosomal dominant variants in the PURA gene or a deletion encompassing the PURA gene. PURA-NDD is clinically characterized by neurodevelopmental delay, learning disability, neonatal hypotonia, feeding difficulties, abnormal movements, and epilepsy. It is generally considered to be central nervous system disorders, with generalized weakness, associated hypotonia, cognitive and development deficits in early development, and seizures in late stages. Although it is classified predominantly as a central nervous syndrome disorder, some phenotypic features, such as myopathic facies, respiratory insufficiency of muscle origin, and myopathic features on muscle biopsy and electrodiagnostic evaluation, point to a peripheral (neuromuscular) source of weakness. Patients with PURA-NDD have been increasingly identified in exome-sequenced cohorts of patients with neuromuscular- and congenital myasthenic syndrome-like phenotypes. Recently, fluctuating weakness noted in a PURA-NDD patient, accompanied by repetitive nerve stimulation abnormalities, suggested the disease to be a channelopathy and, more specifically, a neuromuscular junction disorder. Treatment with pyridostigmine or salbutamol led to clinical improvement of neuromuscular function in two reported cases. The goal of this systematic retrospective review is to highlight the motor symptoms of PURA-NDD, to further describe the neuromuscular phenotype, and to emphasize the role of potential treatment opportunities of the neuromuscular phenotype in the setting of the potential role of PURA protein in the neuromuscular junction and the muscles.
Topics: Humans; Neuromuscular Junction; Myasthenic Syndromes, Congenital; Neurodevelopmental Disorders; Learning Disabilities; Epilepsy; Muscle Hypotonia; Nervous System Malformations; DNA-Binding Proteins; Transcription Factors
PubMed: 36768582
DOI: 10.3390/ijms24032260 -
American Journal of Human Biology : the... 2015This study aims at performing a systematic review and meta-analysis with the studies of genetic admixture inference of Brazilian population and to compare these results... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study aims at performing a systematic review and meta-analysis with the studies of genetic admixture inference of Brazilian population and to compare these results with the genetic admixture levels in other Latin American countries.
METHODS
We searched for articles regarding the estimation of Brazilian genetic admixture published between 1980 and 2014 that used autosomal markers. Then, conducted meta-analyses at the whole-country and regional level. Finally, we compared the results of Brazil with other estimates from other South, Central and North American countries.
RESULTS
We analyzed data from 25 studies in 38 different Brazilian populations. European (EUR) ancestry is the major contributor to the genetic background of Brazilians, followed by African (AFR), and Amerindian (AMR) ancestries. The pooled ancestry contributions were 0.62 EUR, 0.21 AFR, and 0.17AMR. The Southern region had a greater EUR contribution (0.77) than other regions. Individuals from the Northeast (NE) region had the highest AFR contribution (0.27) whereas individuals from the North regions had more AMR contribution (0.32). In the Latin America context, Brazil has the 5th high EUR contribution, the 12th for the AFR component and the 10th for the AMR ancestry.
CONCLUSIONS
Admixture proportions vary greatly among Brazilian populations and also through Latin America. More studies in the Center-West, North and NE regions are needed to capture a more complete picture of the genomic ancestry of Brazil.
Topics: Brazil; Ethnicity; Gene Frequency; Genetic Variation; Humans
PubMed: 25820814
DOI: 10.1002/ajhb.22714 -
The Cochrane Database of Systematic... Nov 2016Thalassemia is an inherited autosomal recessive blood disorder, caused by mutations in globin genes or their regulatory regions. This results in a reduced rate of... (Review)
Review
BACKGROUND
Thalassemia is an inherited autosomal recessive blood disorder, caused by mutations in globin genes or their regulatory regions. This results in a reduced rate of synthesis of one of the globin chains that make up haemoglobin. In ß-thalassaemia major there is an underproduction of ß-globin chains combined with excess of free α-globin chains. The excess free α-globin chains precipitate in red blood cells, leading to their destruction (haemolysis) and ineffective erythropoiesis. The conventional approach to treatment is based on the correction of haemoglobin status through regular blood transfusions and iron chelation therapy for iron overload. Although conventional treatment has the capacity to improve the quality of life of people with ß-thalassaemia major, allogeneic hematopoietic stem cell transplantation is the only currently available procedure which has the curative potential. This is an update of a previously published Cochrane Review.
OBJECTIVES
To evaluate the effectiveness and safety of different types of allogeneic hematopoietic stem cell transplantation, in people with severe transfusion-dependant ß-thalassaemia major, ß-thalassaemia intermedia or ß0/+- thalassaemia variants requiring chronic blood transfusion.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 18 August 2016.
SELECTION CRITERIA
Randomised controlled trials and quasi-randomised controlled trials comparing allogeneic hematopoietic stem cell transplantation with each other or with standard therapy (regular transfusion and chelation regimen).
DATA COLLECTION AND ANALYSIS
Two review authors independently screened studies and had planned to extract data and assess risk of bias using standard Cochrane methodologies but no studies were identified for inclusion.
MAIN RESULTS
No relevant studies were retrieved after a comprehensive search of the literature.
AUTHORS' CONCLUSIONS
We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the effectiveness and safety of different types of allogeneic stem cell transplantation in people with severe transfusion-dependant ß-thalassaemia major or ß0/+- thalassaemia variants requiring chronic blood transfusion. The absence of high-level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately-powered, randomised controlled clinical trials.
Topics: Hematopoietic Stem Cell Transplantation; Humans; beta-Thalassemia
PubMed: 27900772
DOI: 10.1002/14651858.CD008708.pub4 -
Orphanet Journal of Rare Diseases Jun 2023CSF1R mutations cause autosomal-dominant CSF1R-related leukoencephalopathy with axonal spheroids and pigmented glia (CSF1R-ALSP) and autosomal-recessive brain... (Review)
Review
CSF1R mutations cause autosomal-dominant CSF1R-related leukoencephalopathy with axonal spheroids and pigmented glia (CSF1R-ALSP) and autosomal-recessive brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS). The former is increasingly recognized, and disease-modifying therapy was introduced; however, literature is scarce on the latter. This review analyzes BANDDOS and discusses similarities and differences with CSF1R-ALSP.We systematically retrieved and analyzed the clinical, genetic, radiological, and pathological data on the previously reported and our cases with BANDDOS. We identified 19 patients with BANDDOS (literature search according to the PRISMA 2020 guidelines: n = 16, our material: n = 3). We found 11 CSF1R mutations, including splicing (n = 3), missense (n = 3), nonsense (n = 2), and intronic (n = 2) variants and one inframe deletion. All mutations disrupted the tyrosine kinase domain or resulted in nonsense-mediated mRNA decay. The material is heterogenous, and the presented information refers to the number of patients with sufficient data on specific symptoms, results, or performed procedures. The first symptoms occurred in the perinatal period (n = 5), infancy (n = 2), childhood (n = 5), and adulthood (n = 1). Dysmorphic features were present in 7/17 cases. Neurological symptoms included speech disturbances (n = 13/15), cognitive decline (n = 12/14), spasticity/rigidity (n = 12/15), hyperactive tendon reflex (n = 11/14), pathological reflexes (n = 8/11), seizures (n = 9/16), dysphagia (n = 9/12), developmental delay (n = 7/14), infantile hypotonia (n = 3/11), and optic nerve atrophy (n = 2/7). Skeletal deformities were observed in 13/17 cases and fell within the dysosteosclerosis - Pyle disease spectrum. Brain abnormalities included white matter changes (n = 19/19), calcifications (n = 15/18), agenesis of corpus callosum (n = 12/16), ventriculomegaly (n = 13/19), Dandy-Walker complex (n = 7/19), and cortical abnormalities (n = 4/10). Three patients died in infancy, two in childhood, and one case at unspecified age. A single brain autopsy evidenced multiple brain anomalies, absence of corpus callosum, absence of microglia, severe white matter atrophy with axonal spheroids, gliosis, and numerous dystrophic calcifications.In conclusion, BANDDOS presents in the perinatal period or infancy and has a devastating course with congenital brain abnormalities, developmental delay, neurological deficits, osteopetrosis, and dysmorphic features. There is a significant overlap in the clinical, radiological, and neuropathological aspects between BANDDOS and CSF1R-ALSP. As both disorders are on the same continuum, there is a window of opportunity to apply available therapy in CSF1R-ALSP to BANDDOS.
Topics: Humans; Neuroglia; Leukoencephalopathies; Brain; Mutation; Nervous System Malformations; Atrophy
PubMed: 37349768
DOI: 10.1186/s13023-023-02772-9