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Journal of Clinical Neurology (Seoul,... Apr 2021Premanifest mutation carriers with spinocerebellar ataxia (SCA) can exhibit subtle abnormalities before developing ataxia. We summarized the preataxic manifestations of... (Review)
Review
BACKGROUND AND PURPOSE
Premanifest mutation carriers with spinocerebellar ataxia (SCA) can exhibit subtle abnormalities before developing ataxia. We summarized the preataxic manifestations of SCA1, -2, -3, and -6, and their associations with ataxia onset.
METHODS
We included studies of the premanifest carriers of SCA published between January 1998 and December 2019 identified in Scopus and PubMed by searching for terms including 'spinocerebellar ataxia' and several synonyms of 'preataxic manifestation'. We systematically reviewed the results obtained in studies categorized based on clinical, imaging, and laboratory markers.
RESULTS
We finally performed a qualitative analysis of 48 papers. Common preataxic manifestations appearing in multiple SCA subtypes were muscle cramps, abnormal muscle reflexes, instability in gait and posture, lower Composite Cerebellar Functional Severity scores, abnormalities in video-oculography and transcranial magnetic stimulation, and gray-matter loss and volume reduction in the brainstem and cerebellar structures. Also, decreased sensory amplitudes in nerve conduction studies were observed in SCA2. Eotaxin and neurofilament light-chain levels were revealed as sensitive blood biomarkers in SCA3. Concerning potential predictive markers, hyporeflexia and abnormalities of somatosensory evoked potentials showed correlations with the time to ataxia onset in SCA2 carriers. However, no longitudinal data were found for the other SCA gene carriers.
CONCLUSIONS
Our results suggest that preataxic manifestations vary among SCA1, -2, -3, and -6, with some subtypes sharing specific features. Combining various markers into a standardized index for premanifest carriers may be useful for early screening and assessing the risk of disease progression in SCA carriers.
PubMed: 33835738
DOI: 10.3988/jcn.2021.17.2.187 -
Genetics in Medicine : Official Journal... Jul 2010To conduct a systematic review of literature regarding population-based screening for fragile X syndrome in newborns and women of reproductive age, either before or... (Review)
Review
PURPOSE
To conduct a systematic review of literature regarding population-based screening for fragile X syndrome in newborns and women of reproductive age, either before or during pregnancy.
METHODS
Seven electronic databases were searched for English language studies published between January 1991 and November 2009. Data extraction was performed for all included studies. Results were synthesized using a narrative approach.
RESULTS
One article that examined offering newborn screening for fragile X syndrome and 10 that examined the offer of fragile X syndrome screening to women of reproductive age were identified. Two of these articles also addressed psychosocial aspects of population screening for fragile X syndrome such as attitudes to screening and experiences of screening, and a further nine addressed these issues alone. Studies exploring psychosocial issues demonstrated challenges for counseling arising from a lack of awareness or personal experience with fragile X syndrome in the general population.
CONCLUSIONS
Targeted counseling and educational strategies will be essential to support women from the general population. It is crucial that future studies offering screening for fragile X syndrome explore a range of psychosocial aspects in addition to looking at uptake of testing and mutation frequency.
Topics: Female; Fragile X Syndrome; Genetic Testing; Humans; Infant, Newborn; Neonatal Screening; Pregnancy; Prenatal Diagnosis
PubMed: 20548240
DOI: 10.1097/GIM.0b013e3181e38fb6 -
Orphanet Journal of Rare Diseases Jul 2019Hereditary hemochromatosis (HH) is a genetic disorder that causes excess absorption of iron and can lead to a variety of complications including liver cirrhosis,... (Review)
Review
Hereditary hemochromatosis (HH) is a genetic disorder that causes excess absorption of iron and can lead to a variety of complications including liver cirrhosis, arthritis, abnormal skin pigmentation, cardiomyopathy, hypogonadism, and diabetes. Hemojuvelin (HJV) is the causative gene of a rare subtype of HH worldwide. This study aims to systematically review the genotypic and phenotypic spectra of HJV-HH in multiple ethnicities, and to explore the genotype-phenotype correlations. A comprehensive search of PubMed database was conducted. Data were extracted from 57 peer-reviewed original articles including 132 cases with HJV-HH of multiple ethnicities, involving 117 biallelic cases and 15 heterozygotes. Among the biallelic cases, male and female probands of Caucasian ancestry were equally affected, whereas males were more often affected among East Asians (P=1.72×10). Hepatic iron deposition and hypogonadism were the most frequently reported complications. Hypogonadism and arthropathy were more prevalent in Caucasians than in East Asians (P=9.30×10, 1.69×10). Among the recurrent mutations, G320V (45 unrelated cases) and L101P (7 unrelated cases) were detected most frequently and restricted to Caucasians. [Q6H; C321*] was predominant in Chinese patients (6 unrelated cases). I281T (Chinese and Greek), A310G (Brazilian and African American), and R385* (Italian and North African) were reported across different ethnicities. In genotype-phenotype correlation analyses, 91.30% of homozygotes with exon 2-3 mutations developed early-onset HH compared to 66.00% of those with exon 4 mutations (P=2.40×10). Hypogonadism occurred more frequently in homozygotes with missense mutations (72.55%) than in those with nonsense mutations (35.71%; P=2.43×10). Liver biopsy was accepted by more probands with frame-shift or missense mutations (85.71% and 60.78%, respectively) than by those with nonsense mutations (28.57%; P=2.37×10, 3.93×10). The present review suggests that patients' ethnicity, geographical region, and genetic predisposition should be considered in the diagnosis, prognosis and management of HJV-HH.
Topics: Female; Humans; Male; alpha-Galactosidase; Cross-Sectional Studies; Genotype; Hemochromatosis; Mutation; Hemochromatosis Protein
PubMed: 31286966
DOI: 10.1186/s13023-019-1097-2 -
Journal of the Peripheral Nervous... Jun 2022Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy characterised by a high clinical and genetic heterogeneity. While most cases were... (Review)
Review
BACKGROUND AND AIMS
Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy characterised by a high clinical and genetic heterogeneity. While most cases were described in populations with Caucasian ancestry, genetic research on CMT in Africa is scant. Only a few cases of CMT have been reported, mainly from North Africa. The current study aimed to summarise available data on CMT in Africa, with emphasis on the epidemiological, clinical, and genetic features.
METHODS
We searched PubMed, Scopus, Web of Sciences, and the African Journal Online for articles published from the database inception until April 2021 using specific keywords. A total of 398 articles were screened, and 28 fulfilled our selection criteria.
RESULTS
A total of 107 families totalling 185 patients were reported. Most studies were reported from North Africa (n = 22). The demyelinating form of CMT was the commonest subtype, and the phenotype varied greatly between families, and one family (1%) of CMT associated with hearing impairment was reported. The inheritance pattern was autosomal recessive in 91.2% (n = 97/107) of families. CMT-associated variants were reported in 11 genes: LMNA, GDAP1, GJB1, MPZ, MTMR13, MTMR2, PRX, FGD4/FRABIN, PMP22, SH3TC2, and GARS. The most common genes reported are LMNA, GDAP1, and SH3TC2 and have been found mostly in Northern African populations.
INTERPRETATION
This study reveals that CMT is not rare in Africa, and describes the current clinical and genetic profile. The review emphasised the urgent need to invest in genetic research to inform counselling, prevention, and care for CMT in numerous settings on the continent.
Topics: Africa; Charcot-Marie-Tooth Disease; Genes, Recessive; Humans; Microfilament Proteins; Mutation; Phenotype; Proteins
PubMed: 35383421
DOI: 10.1111/jns.12489 -
Ultrasound in Obstetrics & Gynecology :... Jun 2016To explore the outcome in fetuses with prenatal diagnosis of posterior fossa anomalies apparently isolated on ultrasound imaging. (Meta-Analysis)
Meta-Analysis Review
Systematic review and meta-analysis of isolated posterior fossa malformations on prenatal ultrasound imaging (part 1): nomenclature, diagnostic accuracy and associated anomalies.
OBJECTIVE
To explore the outcome in fetuses with prenatal diagnosis of posterior fossa anomalies apparently isolated on ultrasound imaging.
METHODS
MEDLINE and EMBASE were searched electronically utilizing combinations of relevant medical subject headings for 'posterior fossa' and 'outcome'. The posterior fossa anomalies analyzed were Dandy-Walker malformation (DWM), mega cisterna magna (MCM), Blake's pouch cyst (BPC) and vermian hypoplasia (VH). The outcomes observed were rate of chromosomal abnormalities, additional anomalies detected at prenatal magnetic resonance imaging (MRI), additional anomalies detected at postnatal imaging and concordance between prenatal and postnatal diagnoses. Only isolated cases of posterior fossa anomalies - defined as having no cerebral or extracerebral additional anomalies detected on ultrasound examination - were included in the analysis. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for cohort studies. We used meta-analyses of proportions to combine data and fixed- or random-effects models according to the heterogeneity of the results.
RESULTS
Twenty-two studies including 531 fetuses with posterior fossa anomalies were included in this systematic review. The prevalence of chromosomal abnormalities in fetuses with isolated DWM was 16.3% (95% CI, 8.7-25.7%). The prevalence of additional central nervous system (CNS) abnormalities that were missed at ultrasound examination and detected only at prenatal MRI was 13.7% (95% CI, 0.2-42.6%), and the prevalence of additional CNS anomalies that were missed at prenatal imaging and detected only after birth was 18.2% (95% CI, 6.2-34.6%). Prenatal diagnosis was not confirmed after birth in 28.2% (95% CI, 8.5-53.9%) of cases. MCM was not significantly associated with additional anomalies detected at prenatal MRI or detected after birth. Prenatal diagnosis was not confirmed postnatally in 7.1% (95% CI, 2.3-14.5%) of cases. The rate of chromosomal anomalies in fetuses with isolated BPC was 5.2% (95% CI, 0.9-12.7%) and there was no associated CNS anomaly detected at prenatal MRI or only after birth. Prenatal diagnosis of BPC was not confirmed after birth in 9.8% (95% CI, 2.9-20.1%) of cases. The rate of chromosomal anomalies in fetuses with isolated VH was 6.5% (95% CI, 0.8-17.1%) and there were no additional anomalies detected at prenatal MRI (0% (95% CI, 0.0-45.9%)). The proportions of cerebral anomalies detected only after birth was 14.2% (95% CI, 2.9-31.9%). Prenatal diagnosis was not confirmed after birth in 32.4% (95% CI, 18.3-48.4%) of cases.
CONCLUSIONS
DWM apparently isolated on ultrasound imaging is a condition with a high risk for chromosomal and associated structural anomalies. Isolated MCM and BPC have a low risk for aneuploidy or associated structural anomalies. The small number of cases with isolated VH prevents robust conclusions regarding their management from being drawn. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Chromosome Aberrations; Cranial Fossa, Posterior; Dandy-Walker Syndrome; Female; Gestational Age; Humans; Magnetic Resonance Imaging; Nervous System Malformations; Pregnancy; Prenatal Diagnosis; Ultrasonography, Prenatal
PubMed: 25970099
DOI: 10.1002/uog.14900 -
Biology Apr 2023The aim of this review is to identify possible structural abnormalities of BrS and their potential association with symptoms, risk stratification, and prognosis. (1)... (Review)
Review
The aim of this review is to identify possible structural abnormalities of BrS and their potential association with symptoms, risk stratification, and prognosis. (1) Background: BrS has always been considered a purely electrical disease and imaging techniques do not currently play a specific role in the diagnosis of this arrhythmic syndrome. Some authors have recently hypothesized the presence of structural and functional abnormalities. Therefore, several studies investigated the presence of pathological features in echocardiography and cardiac magnetic resonance imaging (MRI) in patients with BrS, but results were controversial. (2) Methods: We performed a systematic review of the literature on the spectrum of features detected by echocardiography and cardiac MRI. Articles were searched in Pubmed, Cochrane Library, and Biomed Central. Only papers published in English and in peer-reviewed journals up to November 2021 were selected. After an initial evaluation, 596 records were screened; the literature search identified 19 relevant articles. (3) Results: The imaging findings associated with BrS were as follows: right ventricular dilation, right ventricular wall motion abnormalities, delayed right ventricular contraction, speckle and feature tracking abnormalities, late gadolinium enhancement, and fat infiltration in the right ventricle. Furthermore, these features emerged more frequently in patients carrying the genetic mutation on the sodium voltage-gated channel α-subunit 5 (SCN5A) gene. (4) Conclusions: Specific imaging features detected by echocardiography and cardiac magnetic resonance are associated with BrS. However, this population appears to be heterogeneous and imaging anomalies emerged to be more frequent in patients carrying genetic mutations of SCN5A. Future studies with an evaluation of BrS patients are needed to identify the specific association linking the Brugada pattern, imaging abnormalities and their possible correlation with prognosis.
PubMed: 37106806
DOI: 10.3390/biology12040606 -
Orphanet Journal of Rare Diseases Sep 2022Hereditary transthyretin amyloidosis (hATTR) is a progressive and fatal disease with heterogenous clinical presentations, limited diagnosis and poor prognosis. This...
BACKGROUND
Hereditary transthyretin amyloidosis (hATTR) is a progressive and fatal disease with heterogenous clinical presentations, limited diagnosis and poor prognosis. This retrospective analysis study aimed to report the genotypes and phenotypes of herediary transthyretin amyloidosis (hATTR) in Chinese through a systematic review of published literature.
METHODS
The systematic review included structured searches of peer-reviewed literature published from 2007 to 2020 of following online reference databases: PubMed, Web of Science and the literature database in China. Extracted data included sample size, personal information (sex, age, natural course, family history), mutation type, clinical milestones and reason of death.
RESULTS
We described 126 Chinese patients with hereditary transthyretin amyloidosis identified through a systematic review of 30 studies. The most common genotype in the Chinese population was Gly83Arg (25, 19.8%), which most likely presented visual and neurological abnormalities without reported death. The second and third most common genotypes were Val30Met (20, 15.9%) and Val30Ala (10, 7.9%). Peripheral neurological manifestations (91, 72%) were dominant in 126 patients. The followed manifestation was autonomic neurological abnormalities (73, 58%). Half of the cases were reported to have visual disorders, and nearly one-third of the cases presented cardiac abnormalities. Among all 126 reported patients, 46.03% were classified as neurological type, 30.16% as mixed type and only 2.38% as cardiac type. In addition. Chinese patients were mostly early onset, with age of onset at 41.8 (SD: 8.9) years, and the median time from onset to death was 7.5 [IQR: 5.3] years. Patients with cardiac involvement had a shorter survival duration (log Rank (Mantel-Cox), χ = 26.885, P < 0.001).
CONCLUSIONS
This study focused on 126 Chinese hATTR patients obtained from a literature review. A total of 26 kinds of TTR mutations were found and the most common one was Gly83Arg. As for phenotype, 46.03% were classified as neurological type, 30.16% as mixed type and only 2.38% as cardiac type. Chinese hATTR patients were mostly early onset (AO 41.8 years), and the median time from onset to death was 7.5 years.
Topics: Amyloid Neuropathies, Familial; Humans; Phenotype; Prealbumin; Retrospective Studies
PubMed: 36056432
DOI: 10.1186/s13023-022-02481-9 -
BMC Medical Genetics Nov 2017It is now well-known that some antimalarials such as primaquine may induce severe hemolytic anemia in people with G-6-PD deficiency. Antimalarial drug prescriptions... (Review)
Review
BACKGROUND
It is now well-known that some antimalarials such as primaquine may induce severe hemolytic anemia in people with G-6-PD deficiency. Antimalarial drug prescriptions must, therefore take into account the patient's G-6-PD status in malaria endemic areas such as Burkina Faso, where the prevalence of this genetic abnormality is relatively high. Although great clinical heterogeneity is observed depending on the molecular nature of the deficiency and the residual enzyme activity in the red blood cell, there is very poor data on the prevalence of G-6-PD deficiency and the distribution of involved genetic variants in Burkina Faso. In this systematic review, we present a synthesis of the various studies carried out on the G-6-PD deficiency in Burkina Faso in order to determine its prevalence, probable distribution of the genetic variants involved and their clinical implications for a national systematic screening policy among the groups most vulnerable to malaria.
METHODS
A systematic review was carried out to analyze available published data on the prevalence, phenotypes and mutations responsible for G-6-PD deficiency in Burkina Faso. The key words used were "G-6-PD deficiency AND Burkina Faso" or "Déficit en G-6-PD AND Burkina Faso" in French. To identify the relevant articles, two independent reviewers reviewed the titles, abstracts and the full text of the selected papers.
RESULTS
An average prevalence of 16.6% (183/1100; CI 95%: 0.145-0.190) and 6.5% (69/1066; CI 95%: 0.051-0.081) of G-6-PD deficiency was found respectively in men and women in this systematic review. Although the predominance (99.8% of G-6-PD deficient cases) of 202A/376G G-6-PD A- variant, the Santamaria and Betica Selma variants were identified in Burkina Faso. Independently of the method used, the enzymatic deficiency was significantly higher in males (2.5-20.5%) compared to females (3.3-12.3%).
CONCLUSION
This systematic review suggests that despite the ubiquity of the 202A/376G G-6-PD A- variant in Burkina Faso, it will be necessary to consider the Santamaria and Betica Selma variants although their frequencies remain to be specified. A systematic screening of the G-6-PD deficiency is also needed to prevent the occurrence of iatrogenic hemolytic accidents.
Topics: Alleles; Burkina Faso; Female; Gene Expression; Gene Frequency; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Haplotypes; Humans; Malaria; Male; Mutation; Prevalence; Protective Factors; Sex Factors
PubMed: 29169341
DOI: 10.1186/s12881-017-0496-2 -
Journal of Thrombosis and Haemostasis :... May 2017Essentials Hypodysfibrinogenemia is rarely reported among the congenital fibrinogen disorders. This first systematic literature review led to identification of 51... (Review)
Review
UNLABELLED
Essentials Hypodysfibrinogenemia is rarely reported among the congenital fibrinogen disorders. This first systematic literature review led to identification of 51 hypodysfibrinogenemic cases. Diagnosis based only on functional/antigenic fibrinogen ratio may be insufficient. Family studies show an incomplete segregation of mutation with the clinical phenotypes.
SUMMARY
Background Hypodysfibrinogenemia is a rare disease characterized by decreased levels of a dysfunctional fibrinogen. It shares features with both hypo- and dysfibrinogenemia, although with specific molecular patterns and clinical phenotypes. Objectives To better define the genetics, the diagnosis and the clinical features of hypodysfibrinogenemia. Patients/Methods A systematic literature search led to 167 records. After removal of duplicates, abstract screening and full-text reviewing, 56 molecular and/or clinical studies were analyzed, including a novel FGB missense mutation in a woman with a mild bleeding phenotype. Results A total of 32 single causative mutations were reported, mainly in the COOH-terminal region of the γ or Aα chains at heterozygous or homozygous state. Seven additional hypodysfibrinogenemias were due to compound heterozygosity. The hypofibrinogenemic phenotypes were a result of an impaired assembly or secretion or an increased clearance of the fibrinogen variant, whereas the dysfibrinogenemic phenotype was mainly a result of a defective fibrin polymerization and an abnormal calcium or tPA binding. Among 51 identified index cases, a functional/antigenic fibrinogen ratio < 0.7 had a sensitivity of 86% for the diagnosis of hypodysfibrinogenemia. Eleven patients (22%) were asymptomatic at time of diagnosis, 23 (45%) had a mild bleeding phenotype with mainly obstetrical or gynecologic-related hemorrhage and 22 (43%) had experienced at least one thrombotic event, including 23 venous and eight arterial thromboses. Conclusions This first systematic review on hypodysfibrinogenemia shows the heterogeneity of causative mutations and that misdiagnosis could occur in relation to the functional and antigenic fibrinogen levels. Family studies reveal an incomplete segregation of the mutation with the clinical phenotype.
Topics: Adult; Afibrinogenemia; Blood Coagulation; Blood Coagulation Tests; DNA Mutational Analysis; Female; Fibrinogen; Genetic Markers; Genetic Predisposition to Disease; Heterozygote; Humans; Mutation, Missense; Phenotype
PubMed: 28211264
DOI: 10.1111/jth.13655 -
Journal of Clinical Medicine Mar 2021Left ventricular noncompaction (LVNC) is a heterogeneous, often hereditary group of diseases, which may have diverse clinical manifestations. This article reviews the... (Review)
Review
Left ventricular noncompaction (LVNC) is a heterogeneous, often hereditary group of diseases, which may have diverse clinical manifestations. This article reviews the risk factors for unfavorable outcomes of LVNC in children, as well as discuss the diagnostic methods and the differences between pediatric and adult LVNC. Through a systematic review of the literature, a total of 1983 articles were outlined; 23 of them met the inclusion criteria. In echocardiography the following have been associated with adverse outcomes in children: Left ventricular ejection fraction, end-diastolic dimension, left ventricular posterior wall compaction, and decreased strains. T-wave abnormalities and increased spatial peak QRS-T angle in ECG, as well as arrhythmia, were observed in children at greater risk. Cardiac magnetic resonance is a valuable tool to identify those with systolic dysfunction and late gadolinium enhancement. Genetic testing appears to help identify children at risk, because mutations in particular genes have been associated with worse outcomes. ECG and imaging tests, such as echocardiography and magnetic resonance, help outline risk factors for unfavorable outcomes of LVNC in children and in identifying outpatients who require more attention. Refining the current diagnostic criteria is crucial to avoid inadequate restrain from physical activity.
PubMed: 33809657
DOI: 10.3390/jcm10061232