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Movement Disorders : Official Journal... Feb 2022Pathogenic variants in 5 genes (GCH1, TH, PTS, SPR, and QDPR), involved in dopamine/tetrahydrobiopterin biosynthesis or recycling, have been linked to Dopa-responsive... (Review)
Review
BACKGROUND
Pathogenic variants in 5 genes (GCH1, TH, PTS, SPR, and QDPR), involved in dopamine/tetrahydrobiopterin biosynthesis or recycling, have been linked to Dopa-responsive dystonia (DRD). Diagnosis and treatment are often delayed due to high between- and within-group variability.
OBJECTIVES
Comprehensively analyzed individual genotype, phenotype, treatment response, and biochemistry information.
METHODS
734 DRD patients and 151 asymptomatic GCH1 mutation carriers were included using an MDSGene systematic literature review and an automated classification approach to distinguish between different forms of monogenic DRDs.
RESULTS
Whereas dystonia, L-Dopa responsiveness, early age at onset, and diurnal fluctuations were identified as red flags, parkinsonism without dystonia was rarely reported (11%) and combined with dystonia in only 18% of patients. While sex was equally distributed in autosomal recessive DRD, there was female predominance in autosomal dominant DYT/PARK-GCH1 patients accompanied by a lower median age at onset and more dystonia in females compared to males. Accordingly, the majority of asymptomatic heterozygous GCH1 mutation carriers (>8 years of age) were males. Multiple other subgroup-specific characteristics were identified, showing high accuracy in the automated classification approach: Seizures and microcephaly were mostly seen in DYT/PARK-PTS, autonomic symptoms appeared commonly in DYT/PARK-TH and DYT/PARK-PTS, and sleep disorders and oculogyric crises in DYT/PARK-SPR. Biochemically, homovanillic acid and 5-hydroxyindoleacetic acid in CSF were reduced in most DRDs, but neopterin and biopterin were increased only in DYT/PARK-PTS and DYT/PARK-SPR. Hyperphenylalaninemia was seen in DYT/PARK-PTS, DYT/PARK-QDPR, and rarely reported in autosomal recessive DYT/PARK-GCH1.
CONCLUSIONS
Our indicators will help to specify diagnosis and accelerate start of treatment. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Dystonia; Dystonic Disorders; Female; GTP Cyclohydrolase; Genotype; Humans; Male; Phenotype
PubMed: 34908184
DOI: 10.1002/mds.28874 -
International Journal of 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 -
Child's Nervous System : ChNS :... Feb 2021Pfeiffer syndrome (PS) is a rare autosomal dominant craniofacial disorder characterized by primary craniosynostosis, midface hypoplasia, and extremities' abnormalities... (Review)
Review
Pfeiffer syndrome (PS) is a rare autosomal dominant craniofacial disorder characterized by primary craniosynostosis, midface hypoplasia, and extremities' abnormalities including syndactyly. The purpose of this article was to review the current knowledge regarding how PS affects the nervous system. Methodologically, we conducted a systematic review of the existing literature concerning involvement of the nervous system in PS. Multiple-suture synostosis is common, and it is the premature fusion and abnormal growth of the facial skeleton's bones that cause the characteristic facial features of these patients. Brain abnormalities in PS can be primary or secondary. Primary anomalies are specific developmental brain defects including disorders of the white matter. Secondary anomalies are the result of skull deformity and include intracranial hypertension, hydrocephalus, and Chiari type I malformation. Spinal anomalies in PS patients include fusion of vertebrae, "butterfly" vertebra, and sacrococcygeal extension. Different features have been observed in different types of this syndrome. Cloverleaf skull deformity characterizes PS type II. The main neurological abnormalities are mental retardation, learning difficulties, and seizures. The tricky neurological examination in severely affected patients makes difficult the early diagnosis of neurological and neurosurgical complications. Prenatal diagnosis of PS is possible either molecularly or by sonography, and the differential diagnosis includes other craniosynostosis syndromes. Knowing how PS affects the nervous system is important, not only for understanding its pathogenesis and determining its prognosis but also for the guidance of decision-making in the various critical steps of its management. The latter necessitates an experienced multidisciplinary team.
Topics: Acrocephalosyndactylia; Brain; Craniosynostoses; Facial Bones; Humans; Hydrocephalus
PubMed: 33083874
DOI: 10.1007/s00381-020-04934-7 -
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 -
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 -
Human Reproduction Update Aug 2021In the decade following the introduction of ICSI, a higher prevalence of de novo chromosome abnormalities, in particular sex chromosome and autosomal structural... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In the decade following the introduction of ICSI, a higher prevalence of de novo chromosome abnormalities, in particular sex chromosome and autosomal structural abnormalities, as well as inherited abnormalities was described in children conceived by ICSI compared to both naturally conceived (NC) children and children conceived by standard IVF. The explanation for the observed increase in prevalence is not clear and has been suggested to reflect parental factors (e.g. age or sperm quality) or to be a result of the ICSI procedure itself. Over the years, the procedure, as well as the patient group, and indications for ICSI treatment have changed.
OBJECTIVE AND RATIONALE
The objective of this systematic review and meta-analysis was to assess the prevalence of chromosome abnormalities in ICSI pregnancies and children and to examine any potentially increased risk compared to standard IVF and NC.
SEARCH METHODS
Pubmed, Embase, Cochrane Libraries and Web of Science up to October 2020 were searched. Primary outcome measures were overall chromosome abnormalities and de novo abnormalities (including sex chromosome abnormalities and autosomal abnormalities). The secondary outcome was inherited abnormalities. We followed the PRISMA guidelines and relevant meta-analyses were performed.
OUTCOMES
The search included 4648 articles, out of which 27 met the inclusion criteria, and 19 were included in quantitative synthesis (meta-analyses). The prevalence of chromosome abnormalities varied considerably between studies, possibly explained by large differences in sample size and patient demographics. Only five studies were eligible for pooled analyses on adjusted data. All studies had a critical risk of bias. Results from pooled adjusted data showed no evidence of an increased risk of overall chromosome abnormalities when comparing ICSI to either standard IVF (aOR 0.75 (95% CI 0.41-1.38)) or NC (aOR 1.29 (95% CI 0.69-2.43)). In contrast, meta-analyses on unadjusted data showed an increased risk of overall chromosome abnormalities in ICSI compared to both standard IVF (OR 1.42 (95% CI 1.09-1.85)) and NC (OR 2.46 (95% CI 1.52-3.99)) and an increased risk of de novo abnormalities in ICSI compared to NC (OR 2.62 (95% CI 2.07-3.31)). Yet, based on a very low certainty of evidence, the conclusion remains, that no indication of an increased risk of chromosome abnormalities in ICSI offspring could be found. If an increased risk of chromosome abnormalities in selected ICSI offspring should exist, the absolute risk continues to be small.
WIDER IMPLICATIONS
This review provides an extensive overview of the existing evidence on the relationship between ICSI and chromosome abnormalities in the offspring. We highlight the need for well-designed large, prospective, controlled studies with systematic cytogenetic testing. Existing data are limited and, in many cases, marred by critical levels of bias.
Topics: Child; Chromosome Aberrations; Female; Fertilization; Fertilization in Vitro; Humans; Pregnancy; Prospective Studies; Sperm Injections, Intracytoplasmic
PubMed: 33956940
DOI: 10.1093/humupd/dmab005 -
Frontiers in Aging Neuroscience 2022To investigate the association between diffusion tensor imaging (DTI) findings and domain-specific cognitive impairment in cerebral small vessel disease (CSVD).
OBJECTIVE
To investigate the association between diffusion tensor imaging (DTI) findings and domain-specific cognitive impairment in cerebral small vessel disease (CSVD).
METHODS
Databases such as PubMed, Excerpta Medical Database (EMBASE), Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure Databases (CNKI), Wanfang, Chinese Biomedical Literature Database (SinoMed), and Chongqing Chinese Science and Technology Periodical Database (VIP) were comprehensively retrieved for studies that reported correlation coefficients between cognition and DTI values. Random effects models and meta-regression were applied to account for heterogeneity among study results. Subgroup and publication bias analyses were performed using Stata software.
RESULTS
Seventy-seven studies involving 6,558 participants were included in our meta-analysis. The diagnosis classification included CSVD, white matter hyperintensities (WMH), subcortical ischemic vascular disease, cerebral microbleeding, cerebral amyloid angiopathy (CAA), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and Fabry disease. The pooled estimates showed that the fractional anisotropy (FA)-overall exhibited a moderate correlation with general cognition, executive function, attention, construction, and motor performance ( = 0.451, 0.339, 0.410, and 0.319), and the mean diffusitivity/apparent diffusion coefficient (MD/ADC)-overall was moderately associated with general cognition, executive function, and memory ( = -0.388, -0.332, and -0.303, respectively; < 0.05). Moreover, FA in cingulate gyrus (CG), cerebral peduncle (CP), corona radiata (CR), external capsule (EC), frontal lobe (FL), fornix (FOR), internal capsule (IC), and thalamic radiation (TR) was strongly correlated with general cognition ( = 0.591, 0.584, 0.543, 0.662, 0.614, 0.543, 0.597, and 0.571), and a strong correlation was found between MD/ADC and CG ( = -0.526), normal-appearing white matter (NAWM; = -0.546), and whole brain white matter (WBWM; = -0.505). FA in fronto-occipital fasciculus (FOF) ( = 0.523) and FL ( = 0.509) was strongly associated with executive function. Only MD/ADC of the corpus callosum (CC) was strongly associated with memory ( = -0.730). Besides, FA in CG ( = 0.532), CC ( = 0.538), and FL ( = 0.732) was strongly related to the attention domain. Finally, we found that the sample size, etiology, magnetic resonance imaging (MRI) magnet strength, study type, and study quality contributed to interstudy heterogeneity.
CONCLUSION
Lower FA or higher MD/ADC values were related to more severe cognitive impairment. General cognition and executive function domains attracted the greatest interest. The FL was commonly examined and strongly associated with general cognition, executive function, and attention. The CC was strongly associated with memory and attention. The CG was strongly related to general cognition and attention. The CR, IC, and TR were also strongly related to general cognition. Indeed, these results should be validated in high-quality prospective studies with larger sample sizes.
SYSTEMATIC REVIEW REGISTRATION
http://www.crd.york.ac.uk/PROSPERO, identifier: CRD42021226133.
PubMed: 36483114
DOI: 10.3389/fnagi.2022.1019088 -
Cureus Apr 2022Pycnodysostosis (PYCD) is an autosomal recessive lysosomal storage disorder of the bone which leads to stereotypical abnormalities consisting of, but not limited to,... (Review)
Review
Pycnodysostosis (PYCD) is an autosomal recessive lysosomal storage disorder of the bone which leads to stereotypical abnormalities consisting of, but not limited to, sclerotic and fragile bone, shortened distal phalanges, and obtuse mandibular angle. Current literature describes the otolaryngological manifestations and treatment of this disorder; however, the treatment of orthopedic fractures in PYCD patients is seldom described and remains a controversial topic. We aim to systematically review the current evidence regarding the optimal treatment of PYCD patients with fractures. We performed a literature search using PubMed, MEDLINE, Web of Science, and Google Scholar databases. Elig-ibility criteria consisted of English-language literature of PYCD patients undergoing treatment for orthopedic surgery fractures. Non-English papers or literature focused on maxillofacial manifestations/treatment were excluded. The database search resulted in the identification of 500 articles. After removing duplicates and enforcing our inclusion criteria, 29 case reports/series (40 patients) were included. The average age was 31.25 (-±18.2) years, with 57.5% of patients being female. Overall, 62.5% of patients had consanguineous parents. Additionally, 86.2% reported a history of previous fractures while 47.5% reported a spontaneous or minor trauma fracture, with most fractures occurring in the femur (60.0%) and tibia (40.0%). Radiographic features consisted of densification in the femur 45.0% (18/40), tibia 37.5% (15/40), and spine 25.0% (10/40). Overall, 84.2% of patients were treated with surgical management consisting of internal plate fixation (IPF) (48.3%), intramedullary fixation (20.7%), and Ilizarov external fixation (IEF) (13.8%). Overall, the refracture rate was 25.0% and was lowest in intramedullary fixation (0/6), compared to IPF (3/14) and IEF (3/4). Average time until refracture was 40.6 months (3-132 months). Long-term follow-up is recommended in patients with PYCD due to the propensity for fractures/refractures. While this study provides the groundwork for the treatment of PYCD patients, further research with higher-evidence studies should be conducted to establish the optimal orthopedic treatment of this disorder.
PubMed: 35602818
DOI: 10.7759/cureus.24275 -
BioMed Research International 2022Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of UV radiation-induced damage repair that is characterized by photosensitivity and a propensity for... (Review)
Review
BACKGROUND
Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of UV radiation-induced damage repair that is characterized by photosensitivity and a propensity for developing, among many others, skin cancers at an early age. This systematic review focused on the correlation between the clinical, pathological, and genetic aspects of XP and skin cancer.
METHODS
A systematic review was conducted through a literature search of online databases PubMed, Cochrane Library, SciELO, and Google Scholar. Search terms were "Xeroderma pigmentosum", "XP", "XPC", "Nucleotide excision repair", "NER", "POLH", "Dry pigmented skin", and "UV sensitive syndrome" meshed with the terms "Skin cancer", "Melanoma", and "NMSC".
RESULTS
After 504 abstracts screening, 13 full-text articles were assessed for eligibility, and 3 of them were excluded. Ten articles were selected for qualitative assessment.
CONCLUSIONS
Patients with XP usually suffer shorter lives due to skin cancer and neurodegenerative disease. Deletion/alteration of a distinct gene allele can produce different types of cancer. The XPC and XP-E variants are more likely to have skin cancer than patients in other complement groups, and the most common cause of death for these patients is skin cancer (metastatic melanoma or invasive SCC). Still, aggressive preventative measures to minimize UV radiation exposure can retard the course of the disease and improve the quality of life.
Topics: DNA Repair; Humans; Ichthyosis; Melanoma; Neurodegenerative Diseases; Quality of Life; Skin Neoplasms; Ultraviolet Rays; Xeroderma Pigmentosum
PubMed: 35898688
DOI: 10.1155/2022/8549532 -
Medicina (Kaunas, Lithuania) Mar 2023: Gaucher disease (GD) is a lysosomal storage disorder with the genetic autosomal recessive transmission. Bone involvement is a prevalent finding in Gaucher disease. It... (Review)
Review
: Gaucher disease (GD) is a lysosomal storage disorder with the genetic autosomal recessive transmission. Bone involvement is a prevalent finding in Gaucher disease. It causes deformity and limits daily activities and the quality of life. In 75% of patients, there is bone involvement. This review aims to evaluate the principal findings in the jaw by a Cone-beam computed tomography (CBTC) and X-ray orthopantomography; : PubMed, Web of Science, Lilacs and Scopus were systematically searched until 31 December 2022. In addition, a manual search was performed using the bibliography of selected articles and a Google Scholar search. Clinical studies were selected that considered principal radiographic findings in radiography in a group of patients affected by GD. : Out of 5079 papers, four studies were included. The main findings are generalized rarefaction and enlarged narrow space, anodontia. : The exact mechanism of bone manifestation is probably due to the infiltration of Gaucher cells in the bone marrow and, consequently, the destruction of bone architecture. All long bones are a potential means of skeletal manifestation. The jaw is more affected than the maxilla, and the principal features are cortical thinning, osteosclerosis, pseudocystic lesions, mental demineralization, flattening in the head of the condyle, effacement of anatomical structures, thickening of maxillary sinus mucosa. The dentist plays a crucial role in diagnosing and treating these patients. Sometimes the diagnosis can be made by a simple panoramic radiograph. All long bones are affected, and the mandible is particularly involved.
Topics: Humans; Gaucher Disease; Quality of Life; Radiography; Cone-Beam Computed Tomography; Bone Marrow
PubMed: 37109627
DOI: 10.3390/medicina59040670