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Survey of Ophthalmology 2023Wolfram-like syndrome (WFLS) is a recently described autosomal dominant disorder with phenotypic similarities to autosomal recessive Wolfram syndrome (WS), including... (Review)
Review
Wolfram-like syndrome (WFLS) is a recently described autosomal dominant disorder with phenotypic similarities to autosomal recessive Wolfram syndrome (WS), including optic atrophy, hearing impairment, and diabetes mellitus. We summarize current literature, define the clinical characteristics, and investigate potential genotype phenotype correlations. A systematic literature search was conducted in electronic databases Pubmed/MEDLINE, EMBACE, and Cochrane Library. We included studies reporting patients with a clinical picture consisting at least 2 typical clinical manifestations of WSF1 disorders and heterozygous mutations in WFS1. In total, 86 patients from 35 studies were included. The most common phenotype consisted of the combination of optic atrophy (87%) and hearing impairment (94%). Diabetes mellitus was seen in 44% of the patients. Nineteen percent developed cataract. Patients with missense mutations in WFS1 had a lower number of clinical manifestations, less chance of developing diabetes insipidus, but a younger age at onset of hearing impairment compared to patients with nonsense mutations or deletions causing frameshift. There were no studies reporting decreased life expectancy. This review shows that, within the spectrum of WFS1-associated disorders or "wolframinopathies," autosomal dominantly inherited WFLS has a relatively mild phenotype compared to autosomal recessive WS. The clinical manifestations and their age at onset are associated with the specific underlying mutations in the WFS1 gene.
Topics: Humans; Hearing Loss; Mutation; Optic Atrophy; Tungsten; Wolfram Syndrome
PubMed: 36764396
DOI: 10.1016/j.survophthal.2023.01.012 -
Tremor and Other Hyperkinetic Movements... 2023Episodic ataxia (EA), characterized by recurrent attacks of cerebellar dysfunction, is the manifestation of a group of rare autosomal dominant inherited disorders. EA1... (Review)
Review
BACKGROUND
Episodic ataxia (EA), characterized by recurrent attacks of cerebellar dysfunction, is the manifestation of a group of rare autosomal dominant inherited disorders. EA1 and EA2 are most frequently encountered, caused by mutations in and . EA3-8 are reported in rare families. Advances in genetic testing have broadened the and phenotypes, and detected EA as an unusual presentation of several other genetic disorders. Additionally, there are various secondary causes of EA and mimicking disorders. Together, these can pose diagnostic challenges for neurologists.
METHODS
A systematic literature review was performed in October 2022 for 'episodic ataxia' and 'paroxysmal ataxia', restricted to publications in the last 10 years to focus on recent clinical advances. Clinical, genetic, and treatment characteristics were summarized.
RESULTS
EA1 and EA2 phenotypes have further broadened. In particular, EA2 may be accompanied by other paroxysmal disorders of childhood with chronic neuropsychiatric features. New treatments for EA2 include dalfampridine and fampridine, in addition to 4-aminopyridine and acetazolamide. There are recent proposals for EA9-10. EA may also be caused by gene mutations associated with chronic ataxias (), epilepsy syndromes (), GLUT-1, mitochondrial disorders (), metabolic disorders (Maple syrup urine disease, Hartnup disease, type I citrullinemia, thiamine and biotin metabolism defects), and others. Secondary causes of EA are more commonly encountered than primary EA (vascular, inflammatory, toxic-metabolic). EA can be misdiagnosed as migraine, peripheral vestibular disorders, anxiety, and functional symptoms. Primary and secondary EA are frequently treatable which should prompt a search for the cause.
DISCUSSION
EA may be overlooked or misdiagnosed for a variety of reasons, including phenotype-genotype variability and clinical overlap between primary and secondary causes. EA is highly treatable, so it is important to consider in the differential diagnosis of paroxysmal disorders. Classical EA1 and EA2 phenotypes prompt single gene test and treatment pathways. For atypical phenotypes, next generation genetic testing can aid diagnosis and guide treatment. Updated classification systems for EA are discussed which may assist diagnosis and management.
Topics: Humans; Ataxia; Cerebellar Ataxia; Acetazolamide; Mutation
PubMed: 37008993
DOI: 10.5334/tohm.747 -
Genetics in Medicine : Official Journal... Jul 2022Noninvasive prenatal screening (NIPS) using cell-free DNA has been assimilated into prenatal care. Prior studies examined clinical validity and technical performance in... (Review)
Review
PURPOSE
Noninvasive prenatal screening (NIPS) using cell-free DNA has been assimilated into prenatal care. Prior studies examined clinical validity and technical performance in high-risk populations. This systematic evidence review evaluates NIPS performance in a general-risk population.
METHODS
Medline (PubMed) and Embase were used to identify studies examining detection of Down syndrome (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies, rare autosomal trisomies, copy number variants, and maternal conditions, as well as studies assessing the psychological impact of NIPS and the rate of subsequent diagnostic testing. Random-effects meta-analyses were used to calculate pooled estimates of NIPS performance (P < .05). Heterogeneity was investigated through subgroup analyses. Risk of bias was assessed.
RESULTS
A total of 87 studies met inclusion criteria. Diagnostic odds ratios were significant (P < .0001) for T21, T18, and T13 for singleton and twin pregnancies. NIPS was accurate (≥99.78%) in detecting sex chromosome aneuploidies. Performance for rare autosomal trisomies and copy number variants was variable. Use of NIPS reduced diagnostic tests by 31% to 79%. Conclusions regarding psychosocial outcomes could not be drawn owing to lack of data. Identification of maternal conditions was rare.
CONCLUSION
NIPS is a highly accurate screening method for T21, T18, and T13 in both singleton and twin pregnancies.
Topics: Cell-Free Nucleic Acids; Down Syndrome; Female; Humans; Noninvasive Prenatal Testing; Pregnancy; Prenatal Diagnosis; Sex Chromosome Aberrations; Trisomy; Trisomy 13 Syndrome; Trisomy 18 Syndrome
PubMed: 35608568
DOI: 10.1016/j.gim.2022.03.019 -
Advances in Kidney Disease and Health May 2023Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. It has been associated with a significant physical and psychological... (Review)
Review
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. It has been associated with a significant physical and psychological burden, leading to a reduced quality of life. The purpose of this literature review is to summarize the patient perspective on ADPKD based on the current published literature. A systematic literature review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Publications reporting a patient or caregiver/relative perspective of ADPKD were included. Sources searched included Medline (PubMed), Embase (Ovid), Cochrane Library, and Web of Science from inception to April 2022. This was followed by a subsequent reference and citation search. A total of 1011 articles were identified by the search process, with 28 studies included in the review. An inductive thematic analysis identified six key themes: diagnosis, monitoring, and screening; symptoms; lifestyle and dietary interventions; psychological, physical, and social impact; future planning; and interaction with the health care system. The findings of this review highlight the burden and uncertainty associated with ADPKD from a patient's perspective. This impacts patients and their caregivers/relatives at each stage of the patient's journey from screening to initiation of renal replacement therapy and future planning.
Topics: Humans; Polycystic Kidney, Autosomal Dominant; Quality of Life; Life Style
PubMed: 37088530
DOI: 10.1053/j.akdh.2023.01.002 -
The Cochrane Database of Systematic... Feb 2021Vascular cognitive impairment (VCI) describes a broad spectrum of cognitive impairments caused by cerebrovascular disease, ranging from mild cognitive impairment to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vascular cognitive impairment (VCI) describes a broad spectrum of cognitive impairments caused by cerebrovascular disease, ranging from mild cognitive impairment to dementia. There are currently no pharmacological treatments recommended for improving either cognition or function in people with VCI. Three cholinesterase inhibitors (donepezil, galantamine, and rivastigmine) are licenced for the treatment of dementia due to Alzheimer's disease. They are thought to work by compensating for reduced cholinergic neurotransmission, which is also a feature of VCI. Through pairwise comparisons with placebo and a network meta-analysis, we sought to determine whether these medications are effective in VCI and whether there are differences between them with regard to efficacy or adverse events.
OBJECTIVES
(1) To assess the efficacy and safety of cholinesterase inhibitors in the treatment of adults with vascular dementia and other VCI. (2) To compare the effects of different cholinesterase inhibitors on cognition and adverse events, using network meta-analysis.
SEARCH METHODS
We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), CINAHL (EBSCOhost), Web of Science Core Collection (ISI Web of Science), LILACS (BIREME), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform on 19 August 2020.
SELECTION CRITERIA
We included randomised controlled trials in which donepezil, galantamine, or rivastigmine was compared with placebo or in which the drugs were compared with each other in adults with vascular dementia or other VCI (excluding cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)). We included all drug doses and routes of administration.
DATA COLLECTION AND ANALYSIS
Two review authors independently identified eligible trials, extracted data, assessed risk of bias, and applied the GRADE approach to assess the certainty of the evidence. The primary outcomes were cognition, clinical global impression, function (performance of activities of daily living), and adverse events. Secondary outcomes were serious adverse events, incidence of development of new dementia, behavioural disturbance, carer burden, institutionalisation, quality of life and death. For the pairwise analyses, we pooled outcome data at similar time points using random-effects methods. We also performed a network meta-analysis using Bayesian methods.
MAIN RESULTS
We included eight trials (4373 participants) in the review. Three trials studied donepezil 5 mg or 10 mg daily (n= 2193); three trials studied rivastigmine at a maximum daily dose of 3 to 12 mg (n= 800); and two trials studied galantamine at a maximum daily dose of 16 to 24 mg (n= 1380). The trials included participants with possible or probable vascular dementia or cognitive impairment following stroke. Mean ages were between 72.2 and 73.9 years. All of the trials were at low or unclear risk of bias in all domains, and the evidence ranged from very low to high level of certainty. For cognition, the results showed that donepezil 5 mg improves cognition slightly, although the size of the effect is unlikely to be clinically important (mean difference (MD) -0.92 Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) points (range 0 to 70), 95% confidence interval (CI) -1.44 to -0.40; high-certainty evidence). Donepezil 10 mg (MD -2.21 ADAS-Cog points, 95% CI -3.07 to -1.35; moderate-certainty evidence) and galantamine 16 to 24 mg (MD -2.01 ADAS-Cog point, 95%CI -3.18 to -0.85; moderate-certainty evidence) probably also improve cognition, although the larger effect estimates still may not be clinically important. With low certainty, there may be little to no effect of rivastigmine 3 to 12 mg daily on cognition (MD 0.03 ADAS-Cog points, 95% CI -3.04 to 3.10; low-certainty evidence). Adverse events reported in the studies included nausea and/or vomiting, diarrhoea, dizziness, headache, and hypertension. The results showed that there was probably little to no difference between donepezil 5 mg and placebo in the number of adverse events (odds ratio (OR) 1.22, 95% CI 0.94 to 1.58; moderate-certainty evidence), but there were slightly more adverse events with donepezil 10 mg than with placebo (OR 1.95, 95% CI 1.20 to 3.15; high-certainty evidence). The effect of rivastigmine 3 to 12 mg on adverse events was very uncertain (OR 3.21, 95% CI 0.36 to 28.88; very low-certainty evidence). Galantamine 16 to 24 mg is probably associated with a slight excess of adverse events over placebo (OR 1.57, 95% CI 1.02 to 2.43; moderate-certainty evidence). In the network meta-analysis (NMA), we included cognition to represent benefit, and adverse events to represent harm. All drugs ranked above placebo for cognition and below placebo for adverse events. We found donepezil 10 mg to rank first in terms of benefit, but third in terms of harms, when considering the network estimates and quality of evidence. Galantamine was ranked second in terms of both benefit and harm. Rivastigmine had the lowest ranking of the cholinesterase inhibitors in both benefit and harm NMA estimates, but this may reflect possibly inadequate doses received by some trial participants and small trial sample sizes.
AUTHORS' CONCLUSIONS
We found moderate- to high-certainty evidence that donepezil 5 mg, donepezil 10 mg, and galantamine have a slight beneficial effect on cognition in people with VCI, although the size of the change is unlikely to be clinically important. Donepezil 10 mg and galantamine 16 to 24 mg are probably associated with more adverse events than placebo. The evidence for rivastigmine was less certain. The data suggest that donepezil 10 mg has the greatest effect on cognition, but at the cost of adverse effects. The effect is modest, but in the absence of any other treatments, people living with VCI may still wish to consider the use of these agents. Further research into rivastigmine is needed, including the use of transdermal patches.
Topics: Activities of Daily Living; Bias; Cholinesterase Inhibitors; Cognition; Dementia, Vascular; Donepezil; Galantamine; Humans; Network Meta-Analysis; Nootropic Agents; Physical Functional Performance; Placebos; Randomized Controlled Trials as Topic; Rivastigmine
PubMed: 33704781
DOI: 10.1002/14651858.CD013306.pub2 -
Cerebellum (London, England) Jun 2024Spinocerebellar ataxias (SCAs) are a heterogenous group of rare neurodegenerative conditions sharing an autosomal dominant pattern of inheritance. More than 40 SCAs have... (Review)
Review
Spinocerebellar ataxias (SCAs) are a heterogenous group of rare neurodegenerative conditions sharing an autosomal dominant pattern of inheritance. More than 40 SCAs have been genetically determined. However, a systematic review of SCA epidemiology in Europe is still missing. Here we performed a narrative review of the literature on the epidemiology of the most common SCAs in Europe. PubMed, Embase, and MEDLINE were searched from inception until 1 April 2023. All English peer-reviewed articles published were considered and then filtered by abstract examination and subsequently by full text reading. A total of 917 original articles were retrieved. According to the inclusion criteria and after reviewing references for useful papers, a total of 35 articles were included in the review. Overall, SCA3 is the most frequent spinocerebellar ataxia in Europe. Its frequency is strikingly higher in Portugal, followed by Germany, France, and Netherlands. None or few cases were described in Italy, Russia, Poland, Serbia, Finland, and Norway. SCA1 and SCA2 globally displayed similar frequencies, and are more prevalent in Italy, United Kingdom, Poland, Serbia, and France.
Topics: Humans; Spinocerebellar Ataxias; Europe; Prevalence
PubMed: 37698771
DOI: 10.1007/s12311-023-01600-x -
Orphanet Journal of Rare Diseases Jun 2021Progressive familial intrahepatic cholestasis is a rare, heterogeneous group of liver disorders of autosomal recessive inheritance, characterised by an early onset of... (Review)
Review
BACKGROUND
Progressive familial intrahepatic cholestasis is a rare, heterogeneous group of liver disorders of autosomal recessive inheritance, characterised by an early onset of cholestasis with pruritus and malabsorption, which rapidly progresses, eventually culminating in liver failure. For children and their parents, PFIC is an extremely distressing disease. Significant pruritus can lead to severe cutaneous mutilation and may affect many activities of daily living through loss of sleep, irritability, poor attention, and impaired school performance.
METHODS
Databases including MEDLINE and Embase were searched for publications on PFIC prevalence, incidence or natural history, and the economic burden or health-related quality of life of patients with PFIC. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.
RESULTS
Three systematic reviews and twenty-two studies were eligible for inclusion for the epidemiology of PFIC including a total of 2603 patients. Study periods ranged from 3 to 33 years. Local population prevalence of PFIC was reported in three studies, ranging from 9.0 to 12.0% of children admitted with cholestasis, acute liver failure, or splenomegaly. The most detailed data come from the NAPPED study where native liver survival of >15 years is predicted in PFIC2 patients with a serum bile acid concentration below 102 µmol/L following bile diversion surgery. Burden of disease was mainly reported through health-related quality of life (HRQL), rates of surgery and survival. Rates of biliary diversion and liver transplant varied widely depending on study period, sample size and PFIC type, with many patients have multiple surgeries and progressing to liver transplant. This renders data unsuitable for comparison.
CONCLUSION
Using robust and transparent methods, this systematic review summarises our current knowledge of PFIC. The epidemiological overview is highly mixed and dependent on presentation and PFIC subtype. Only two studies reported HRQL and mortality results were variable across different subtypes. Lack of data and extensive heterogeneity severely limit understanding across this disease area, particularly variation around and within subtypes.
Topics: Activities of Daily Living; Child; Cholestasis; Cholestasis, Intrahepatic; Humans; Quality of Life
PubMed: 34082807
DOI: 10.1186/s13023-021-01884-4 -
International Journal of Environmental... Feb 2022Ehlers-Danlos syndrome type arthrochalasia (aEDS) is a rare genetic disease characterized by severe generalized joint hypermobility, bilateral congenital hip... (Review)
Review
Ehlers-Danlos syndrome type arthrochalasia (aEDS) is a rare genetic disease characterized by severe generalized joint hypermobility, bilateral congenital hip dislocation, skin hyperextensibility, muscle hypotonia, and mild dysmorphic features. It is an autosomal dominant connective tissue disease causing defects in collagen, associated with two genes, COL1A1 or COL1A2. Only about 42 cases have been published worldwide. Treatment is currently symptomatic and focuses on increasing the quality of life of these patients, as there is no curative treatment. The main objective of the review was to update information on Ehlers-Danlos syndrome type arthrochalasia from scientific publications. The review report was carried out in accordance with the criteria of the Preferred Reporting Items for Systematic reviews and MetaAnalyses (PRISMA) review protocol, by searching Orphanet, OMIM, PubMed, and Scopus, as well as free sources. A total of 20 articles were analyzed, which, after analysis, provide an updated report that aims to establish a solid starting point for future lines of research.
Topics: Collagen; Ehlers-Danlos Syndrome; Humans; Joint Instability; Quality of Life; Skin Abnormalities
PubMed: 35162892
DOI: 10.3390/ijerph19031870 -
Indian Journal of Nephrology 2021The enamel renal syndrome (ERS) is a rare autosomal recessive disease that is associated with mutations in the gene. The syndrome is characterized by impaired... (Review)
Review
The enamel renal syndrome (ERS) is a rare autosomal recessive disease that is associated with mutations in the gene. The syndrome is characterized by impaired amelogenesis of the hypoplastic type and nephrocalcinosis, presenting with presence of thin or absence of enamel, late dental eruption, intrapulpal calcifications, bilateral nephrocalcinosis, and normal plasma calcium level. The objective is to characterize ERS by systematically literature reviewing, highlighting the main findings of the syndrome to increase knowledge about this condition in the health professionals. The study is a systematic review of the scientific literature, whose research was developed in the PubMed database in March 2018. A total of 69 articles were found. Two authors analyzed their abstracts and selected, according to the language and main subject, 30 articles to write this study. A total of 69 patients were cited in the studies and their data were analysed. There was gender equivalence and the ages ranged from 1 to 64 years old. There is a clear hereditary relation of the syndrome, since there was consanguinity in 18 cases, indicating a percentage of 26.08% and family history in 30 cases (43.47%). Laboratory changes vary greatly from patient to patient and may even remain unchanged. The relationship between the syndrome and the mutation in the gene can be proven from the data, since all patients with ERS screened by the mutation were positive. With the advancement of the ERS studies, some associations with the syndrome are suspected, such as the presence of gingival fibromatosis, hearing loss, and hypertrichosis. Thus, it is noticed that the syndrome does not show a predilection for gender or age and there is a strong hereditary character, marked by the consanguinity and family history of the patients. The association with the gene is reinforced, since the mutation was identified in all patients analyzed.
PubMed: 33994680
DOI: 10.4103/ijn.IJN_27_19 -
The Cochrane Database of Systematic... Jun 2020Classical galactosaemia is an autosomal recessive inborn error of metabolism caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase. This is a rare...
BACKGROUND
Classical galactosaemia is an autosomal recessive inborn error of metabolism caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase. This is a rare and potentially lethal condition that classically presents in the first week of life once milk feeds have commenced. Affected babies may present with any or all of the following: cataracts; fulminant liver failure; prolonged jaundice; or Escherichia coli sepsis. Once the diagnosis is suspected, feeds containing galactose must be stopped immediately and replaced with a soya-based formula. The majority of babies will recover, however a number will not survive. There are long-term complications of galactosaemia, despite treatment, including learning disabilities and female infertility. It has been postulated that galactosaemia could be detected on newborn screening and this would prevent the immediate severe liver dysfunction and sepsis. This is an update of a previously published review.
OBJECTIVES
To assess whether there is evidence that newborn screening for galactosaemia prevents or reduces mortality and morbidity and improves clinical outcomes in affected neonates and the quality of life in older children.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from electronic database searches, handsearches of relevant journals and conference abstract books. We also searched online trials registries and the reference lists of relevant articles and reviews. Date of the most recent search of Cochrane Cystic Fibrosis Group's Trials Register: 12 December 2019. Date of the most recent search of additional resources: 02 February 2020.
SELECTION CRITERIA
Randomised controlled studies and controlled clinical studies, published or unpublished comparing the use of any newborn screening test to diagnose infants with galactosaemia and presenting a comparison between a screened population versus a non-screened population.
DATA COLLECTION AND ANALYSIS
No studies of newborn screening for galactosaemia were found.
MAIN RESULTS
No studies were identified for inclusion in the review.
AUTHORS' CONCLUSIONS
We were unable to identify any eligible studies for inclusion in this review and hence it is not possible to draw any conclusions based on randomised controlled studies. However, we are aware of uncontrolled studies which support the efficacy of newborn screening for galactosaemia. There are a number of reviews and economic analyses of non-trial literature suggesting that screening is appropriate.
Topics: Galactosemias; Humans; Infant, Newborn; Neonatal Screening
PubMed: 32567677
DOI: 10.1002/14651858.CD012272.pub3