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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 -
Gut Jul 2010Peutz-Jeghers syndrome (PJS, MIM175200) is an autosomal dominant condition defined by the development of characteristic polyps throughout the gastrointestinal tract and...
Peutz-Jeghers syndrome (PJS, MIM175200) is an autosomal dominant condition defined by the development of characteristic polyps throughout the gastrointestinal tract and mucocutaneous pigmentation. The majority of patients that meet the clinical diagnostic criteria have a causative mutation in the STK11 gene, which is located at 19p13.3. The cancer risks in this condition are substantial, particularly for breast and gastrointestinal cancer, although ascertainment and publication bias may have led to overestimates in some publications. Current surveillance protocols are controversial and not evidence-based, due to the relative rarity of the condition. Initially, endoscopies are more likely to be done to detect polyps that may be a risk for future intussusception or obstruction rather than cancers, but surveillance for the various cancers for which these patients are susceptible is an important part of their later management. This review assesses the current literature on the clinical features and management of the condition, genotype-phenotype studies, and suggested guidelines for surveillance and management of individuals with PJS. The proposed guidelines contained in this article have been produced as a consensus statement on behalf of a group of European experts who met in Mallorca in 2007 and who have produced guidelines on the clinical management of Lynch syndrome and familial adenomatous polyposis.
Topics: Adult; Aged; Breast Neoplasms; Child; Child, Preschool; Endoscopy, Gastrointestinal; Evidence-Based Medicine; Female; Gastrointestinal Neoplasms; Genital Neoplasms, Female; Genotype; Humans; Long-Term Care; Male; Mass Screening; Middle Aged; Peutz-Jeghers Syndrome; Phenotype; Population Surveillance; Young Adult
PubMed: 20581245
DOI: 10.1136/gut.2009.198499 -
Neuroepidemiology 2014Hereditary cerebellar ataxias (HCA) and hereditary spastic paraplegias (HSP) are two groups of neurodegenerative disorders that usually present with progressive gait... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hereditary cerebellar ataxias (HCA) and hereditary spastic paraplegias (HSP) are two groups of neurodegenerative disorders that usually present with progressive gait impairment, often leading to permanent disability. Advances in genetic research in the last decades have improved their diagnosis and brought new possibilities for prevention and future treatments. Still, there is great uncertainty regarding their global epidemiology.
SUMMARY
Our objective was to assess the global distribution and prevalence of HCA and HSP by a systematic review and meta-analysis of prevalence studies. The MEDLINE, ISI Web of Science and Scopus databases were searched (1983-2013) for studies performed in well-defined populations and geographical regions. Two independent reviewers assessed the studies and extracted data and predefined methodological parameters. Overall, 22 studies were included, reporting on 14,539 patients from 16 countries. Multisource population-based studies yielded higher prevalence values than studies based primarily on hospitals or genetic centres. The prevalence range of dominant HCA was 0.0-5.6/10(5), with an average of 2.7/10(5) (1.5-4.0/10(5)). Spinocerebellar ataxia type 3 (SCA3)/Machado-Joseph disease was the most common dominant ataxia, followed by SCA2 and SCA6. The autosomal recessive (AR) HCA (AR-HCA) prevalence range was 0.0-7.2/10(5), the average being 3.3/10(5) (1.8-4.9/10(5)). Friedreich ataxia was the most frequent AR-HCA, followed by ataxia with oculomotor apraxia or ataxia-telangiectasia. The prevalence of autosomal dominant (AD) HSP (AD-HSP) ranged from 0.5 to 5.5/10(5) and that of AR-HSP from 0.0 to 5.3/10(5), with pooled averages of 1.8/10(5) (95% CI: 1.0-2.7/10(5)) and 1.8/10(5) (95% CI: 1.0-2.6/10(5)), respectively. The most common AD-HSP form in every population was spastic paraplegia, autosomal dominant, type 4 (SPG4), followed by SPG3A, while SPG11 was the most frequent AR-HSP, followed by SPG15. In population-based studies, the number of families without genetic diagnosis after systematic testing ranged from 33 to 92% in the AD-HCA group, and was 40-46% in the AR-HCA, 45-67% in the AD-HSP and 71-82% in the AR-HSP groups.
KEY MESSAGES
Highly variable prevalence values for HCA and HSP are reported across the world. This variation reflects the different genetic make-up of the populations, but also methodological heterogeneity. Large areas of the world remain without prevalence studies. From the available data, we estimated that around 1:10,000 people are affected by HCA or HSP. In spite of advances in genetic research, most families in population-based series remain without identified genetic mutation after extensive testing. © 2014 S. Karger AG, Basel.
Topics: Cerebellar Ataxia; Cross-Sectional Studies; Humans; Paraplegia; Prevalence; Spastic Paraplegia, Hereditary; Spinocerebellar Degenerations
PubMed: 24603320
DOI: 10.1159/000358801 -
The Lancet. Neurology Jul 2011Unruptured intracranial aneurysms (UIAs) are increasingly detected and are an important health-care burden. We aimed to assess the prevalence of UIAs according to family... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Unruptured intracranial aneurysms (UIAs) are increasingly detected and are an important health-care burden. We aimed to assess the prevalence of UIAs according to family history, comorbidity, sex, age, country, and time period.
METHODS
Through searches of PubMed, Embase, and Web of Science we updated our 1998 systematic review up to March, 2011. We calculated prevalences and prevalence ratios (PRs) with random-effects binomial meta-analysis. We assessed time trends with year of study as a continuous variable.
FINDINGS
We included 68 studies, which reported on 83 study populations and 1450 UIAs in 94 912 patients from 21 countries. The overall prevalence was estimated as 3·2% (95% CI 1·9-5·2) in a population without comorbidity, with a mean age of 50 years, and consisting of 50% men. Compared with populations without the comorbidity, PRs were 6·9 (95% CI 3·5-14) for autosomal dominant polycystic kidney disease (ADPKD), 3·4 (1·9-5·9) for a positive family history of intracranial aneurysm of subarachnoid haemorrhage, 3·6 (0·4-30) for brain tumour, 2·0 (0·9-4·6) for pituitary adenoma, and 1·7 (0·9-3·0) for atherosclerosis. The PR for women compared with men was 1·61 (1·02-2·54), with a ratio of 2·2 (1·3-3·6) in study populations with a mean age of more than 50 years. Compared with patients older than 80 years, we found no differences by age, except for patients younger than 30 years (0·01, 0·00-0·12). Compared with the USA, PRs were similar for other countries, including Japan (0·8, 0·4-1·7) and Finland (1·0, 0·4-2·4). There was no statistically significant time trend.
INTERPRETATION
The prevalence of UIAs is higher in patients with ADPKD or a positive family history of intracranial aneurysm of subarachnoid haemorrhage than in people without comorbidity. In Finland and Japan, the higher incidence of subarachnoid haemorrhage is not explained by a higher prevalence of UIAs, implicating higher risks of rupture.
FUNDING
Julius Centre for Health Sciences and Primary Care and Department of Neurology and Neurosurgery, University Medical Centre, Utrecht.
Topics: Adult; Age Factors; Comorbidity; Female; Humans; Intracranial Aneurysm; Male; Prevalence; Risk Factors; Sex Factors
PubMed: 21641282
DOI: 10.1016/S1474-4422(11)70109-0 -
Orphanet Journal of Rare Diseases Feb 2019Congenital myasthenic syndromes (CMSs) are a genotypically and phenotypically heterogeneous group of neuromuscular disorders, which have in common an impaired...
OBJECTIVES
Congenital myasthenic syndromes (CMSs) are a genotypically and phenotypically heterogeneous group of neuromuscular disorders, which have in common an impaired neuromuscular transmission. Since the field of CMSs is steadily expanding, the present review aimed at summarizing and discussing current knowledge and recent advances concerning the etiology, clinical presentation, diagnosis, and treatment of CMSs.
METHODS
Systematic literature review.
RESULTS
Currently, mutations in 32 genes are made responsible for autosomal dominant or autosomal recessive CMSs. These mutations concern 8 presynaptic, 4 synaptic, 15 post-synaptic, and 5 glycosilation proteins. These proteins function as ion-channels, enzymes, or structural, signalling, sensor, or transporter proteins. The most common causative genes are CHAT, COLQ, RAPSN, CHRNE, DOK7, and GFPT1. Phenotypically, these mutations manifest as abnormal fatigability or permanent or fluctuating weakness of extra-ocular, facial, bulbar, axial, respiratory, or limb muscles, hypotonia, or developmental delay. Cognitive disability, dysmorphism, neuropathy, or epilepsy are rare. Low- or high-frequency repetitive nerve stimulation may show an abnormal increment or decrement, and SF-EMG an increased jitter or blockings. Most CMSs respond favourably to acetylcholine-esterase inhibitors, 3,4-diamino-pyridine, salbutamol, albuterol, ephedrine, fluoxetine, or atracurium.
CONCLUSIONS
CMSs are an increasingly recognised group of genetically transmitted defects, which usually respond favorably to drugs enhancing the neuromuscular transmission. CMSs need to be differentiated from neuromuscular disorders due to muscle or nerve dysfunction.
Topics: Cholinesterase Inhibitors; Humans; Mutation; Myasthenic Syndromes, Congenital; Neuromuscular Agents; Proteins
PubMed: 30808424
DOI: 10.1186/s13023-019-1025-5 -
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 -
Muscle & Nerve Mar 2012Pompe disease is a rare, autosomal recessive disorder caused by deficiency of the glycogen-degrading lysosomal enzyme acid alpha-glucosidase. Late-onset Pompe disease is... (Review)
Review
INTRODUCTION
Pompe disease is a rare, autosomal recessive disorder caused by deficiency of the glycogen-degrading lysosomal enzyme acid alpha-glucosidase. Late-onset Pompe disease is a multisystem condition, with a heterogeneous clinical presentation that mimics other neuromuscular disorders.
METHODS
Objective is to propose consensus-based treatment and management recommendations for late-onset Pompe disease.
METHODS
A systematic review of the literature by a panel of specialists with expertise in Pompe disease was undertaken.
CONCLUSIONS
A multidisciplinary team should be involved to properly treat the pulmonary, neuromuscular, orthopedic, and gastrointestinal elements of late-onset Pompe disease. Presymptomatic patients with subtle objective signs of Pompe disease (and patients symptomatic at diagnosis) should begin treatment with enzyme replacement therapy (ERT) immediately; presymptomatic patients without symptoms or signs should be observed without use of ERT. After 1 year of ERT, patients' condition should be reevaluated to determine whether ERT should be continued.
Topics: Consensus; Databases, Bibliographic; Disease Progression; Glycogen Storage Disease Type II; Guidelines as Topic; History, 20th Century; Humans
PubMed: 22173792
DOI: 10.1002/mus.22329 -
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 -
The Journal of Clinical Endocrinology... Oct 2019This mini-review offers an update on the rare autoimmune polyendocrinopathy (AP) syndrome with a synopsis of recent developments.
CONTEXT
This mini-review offers an update on the rare autoimmune polyendocrinopathy (AP) syndrome with a synopsis of recent developments.
DESIGN AND RESULTS
Systematic search for studies related to pathogenesis, immunogenetics, screening, diagnosis, clinical spectrum, and epidemiology of AP. AP (orphan code ORPHA 282196) is defined as the autoimmune-induced failure of at least two glands. AP is divided into the rare juvenile type I and the adult types II to IV. The prevalence is 1:100,000 and 1:20,000 for types I and types II to IV, respectively. Whereas type I (ORPHA 3453) is a monogenetic syndrome with an autosomal recessive transmission related to mutations in the autoimmune regulator (AIRE) gene, types II to IV are genetically complex multifactorial syndromes that are strongly associated with certain alleles of HLA genes within the major histocompatibility complex located on chromosome 6, as well as the cytotoxic T lymphocyte antigen 4 and the protein tyrosine phosphatase nonreceptor type 22 genes. Addison disease is the major endocrine component of type II (ORPHA 3143), whereas the coexistence of type 1 diabetes and autoimmune thyroid disease is characteristic for type III (ORPHA 227982). Genetic screening for the AIRE gene is useful in patients with suspected type I, whereas serological screening (i.e., diabetes/adrenal antibodies) is required in patients with monoglandular autoimmunity and suspected AP. If positive, functional endocrine testing of the antibody-positive patients as well as serological screening of their first-degree relatives is recommended.
CONCLUSION
Timely diagnosis, genetic counseling, and optimal long-term management of AP is best offered in specialized centers.
Topics: Adult; Autoimmunity; Child; Comorbidity; Genetic Counseling; Genetic Testing; Humans; Long-Term Care; Polyendocrinopathies, Autoimmune; Prevalence
PubMed: 31127843
DOI: 10.1210/jc.2019-00602