Front Oncol. 2021 Sep 30;11:701400. doi: 10.3389/fonc.2021.701400. eCollection 2021.

ABSTRACT

BACKGROUND: The biliary tree is a rare location of pediatric rhabdomyosarcoma. Due to the low incidence, there is a lack of evidence concerning therapeutic guidelines for this tumor location. In particular, the impact of surgery is discussed controversially.

PURPOSE: Objective is to generate evidence-based treatment guidelines for pediatric biliary rhabdomyosarcoma (BRMS). All available published data on therapeutic regimens and important prognostic factors are investigated with a focus on the role of surgery.

METHODS: A systematic literature search of MEDLINE, Web of Science, and CENTRAL was performed. Patient data were entered individually. Data was pooled and qualitative and quantitative analyses of demographic data, therapy, postoperative/interventional outcomes, relapse, and survival were conducted. In an individual patient data analysis, cox regression was applied to identify key factors predicting the outcome of patients with BRMS.

RESULTS: 65 studies met the inclusion criteria, providing data on 176 patients with BRMS. Individual patient data analysis showed a 5-year overall survival and progression-free survival of 51% and 50% for the total study population. For patients treated after 2000, 5-year OS and PFS was 65% and 59%, respectively. Absence of surgical tumor resection was an independent risk factor for death (Hazard ratio 8.9, 95%-CI 1.8-43.6, p = 0.007) and significantly associated with recurrent disease and disease-related death.

CONCLUSION: This analysis provides comprehensive information on the largest number of patients hitherto reported in the literature. BRMS is still associated with high morbidity and mortality. Surgical tumor resection is essential for appropriate oncological treatment of BRMS. International cooperation studies are needed to enhance evidence and improve the outcome of this orphan disease.

PROTOCOL REGISTRATION: PROSPERO (CRD42021228911) https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021228911.

PMID:34660271 | PMC:PMC8515851 | DOI:10.3389/fonc.2021.701400

BMJ Case Rep. 2021 Oct 13;14(10):e244350. doi: 10.1136/bcr-2021-244350.

ABSTRACT

Anterior megalophthalmos usually presents early in life with megalocornea, deep anterior chamber, raised intraocular pressure, glaucomatous optic nerve damage and iridodonesis/stromal thinning with positive family history. We report atypical features and presentations in two patients (four eyes) with non-familial megalophthalmos. While the first patient, a male, presented at 51 years of age with megalocornea, cataract, phacodonesis, normal pupillary dilatation/normal iris and advanced glaucoma, the second patient presented with iridodonesis with stromal thinning, aphakia and advanced glaucoma. The family history was negative in both patients. The vitreous index was unusually high, >70% in all four eyes, owing to aphakia in the second patient and possible late presentation/variant phenotype in the first patient. Thus, atypical features such as greater vitreous length, absent iris involvement and late-onset adult presentation are common in non-familial anterior megalophthalmos. Clinical surprises due to varied phenotypes should be kept in mind in such cases.

PMID:34645626 | DOI:10.1136/bcr-2021-244350

JTCVS Tech. 2021 Aug 4;9:40-41. doi: 10.1016/j.xjtc.2021.07.022. eCollection 2021 Oct.

NO ABSTRACT

PMID:34647054 | PMC:PMC8501244 | DOI:10.1016/j.xjtc.2021.07.022

Cureus. 2021 Sep 1;13(9):e17649. doi: 10.7759/cureus.17649. eCollection 2021 Sep.

ABSTRACT

Adiposis dolorosa, also known as Dercum's disease, is a rare disorder characterized by debilitating painful lipomas throughout the body. The prevalence and etiology of Dercum's disease are unknown as mentioned in the National Organization of Rare Disorders. We present an interesting case of Dercum's disease in a 53-year-old female who initially presented with a six-week history of painful subcutaneous masses. Ultrasound findings were suggestive of lipomas, however, her symptoms were debilitating beyond that of benign lipomas. She then represented with a rapidly increasing number of soft tissue masses manifesting throughout her body, as well as significant diffuse pain concentrating around these lesions within a short period of time following her initial presentation. The patient underwent surgical excision of a select number of these masses, with histopathology consistent with lipomas. Most cases of Dercum's disease are sporadic, and no guidelines exist regarding the treatment of the disease. Due to the rarity of this condition, in conjunction with simple lipomas typically presenting as painless masses, many patients may be misdiagnosed and neglected due to being falsely labeled as pain seeking or having their symptoms attributed to psychological disorders. Management, therefore, is complex and currently consists of a multidisciplinary approach employing multimodal treatments, including pain control, surgical excision, and psychotherapy. Although this condition has been described in the literature for over 100 years, there have been minimal advancements towards alleviating the suffering of these patients. We aimed to unearth and bring to light the reality and the suffering experienced by patients with Decrum's disease.

PMID:34646696 | PMC:PMC8486361 | DOI:10.7759/cureus.17649

Genome Med. 2021 Oct 14;13(1):153. doi: 10.1186/s13073-021-00965-0.

ABSTRACT

BACKGROUND: Clinical interpretation of genetic variants in the context of the patient's phenotype is becoming the largest component of cost and time expenditure for genome-based diagnosis of rare genetic diseases. Artificial intelligence (AI) holds promise to greatly simplify and speed genome interpretation by integrating predictive methods with the growing knowledge of genetic disease. Here we assess the diagnostic performance of Fabric GEM, a new, AI-based, clinical decision support tool for expediting genome interpretation.

METHODS: We benchmarked GEM in a retrospective cohort of 119 probands, mostly NICU infants, diagnosed with rare genetic diseases, who received whole-genome or whole-exome sequencing (WGS, WES). We replicated our analyses in a separate cohort of 60 cases collected from five academic medical centers. For comparison, we also analyzed these cases with current state-of-the-art variant prioritization tools. Included in the comparisons were trio, duo, and singleton cases. Variants underpinning diagnoses spanned diverse modes of inheritance and types, including structural variants (SVs). Patient phenotypes were extracted from clinical notes by two means: manually and using an automated clinical natural language processing (CNLP) tool. Finally, 14 previously unsolved cases were reanalyzed.

RESULTS: GEM ranked over 90% of the causal genes among the top or second candidate and prioritized for review a median of 3 candidate genes per case, using either manually curated or CNLP-derived phenotype descriptions. Ranking of trios and duos was unchanged when analyzed as singletons. In 17 of 20 cases with diagnostic SVs, GEM identified the causal SVs as the top candidate and in 19/20 within the top five, irrespective of whether SV calls were provided or inferred ab initio by GEM using its own internal SV detection algorithm. GEM showed similar performance in absence of parental genotypes. Analysis of 14 previously unsolved cases resulted in a novel finding for one case, candidates ultimately not advanced upon manual review for 3 cases, and no new findings for 10 cases.

CONCLUSIONS: GEM enabled diagnostic interpretation inclusive of all variant types through automated nomination of a very short list of candidate genes and disorders for final review and reporting. In combination with deep phenotyping by CNLP, GEM enables substantial automation of genetic disease diagnosis, potentially decreasing cost and expediting case review.

PMID:34645491 | DOI:10.1186/s13073-021-00965-0

Int J Mol Sci. 2021 Oct 8;22(19):10891. doi: 10.3390/ijms221910891.

ABSTRACT

Rare diseases (RDs) concern a broad range of disorders and can result from various origins. For a long time, the scientific community was unaware of RDs. Impressive progress has already been made for certain RDs; however, due to the lack of sufficient knowledge, many patients are not diagnosed. Nowadays, the advances in high-throughput sequencing technologies such as whole genome sequencing, single-cell and others, have boosted the understanding of RDs. To extract biological meaning using the data generated by these methods, different analysis techniques have been proposed, including machine learning algorithms. These methods have recently proven to be valuable in the medical field. Among such approaches, unsupervised learning methods via neural networks including autoencoders (AEs) or variational autoencoders (VAEs) have shown promising performances with applications on various type of data and in different contexts, from cancer to healthy patient tissues. In this review, we discuss how AEs and VAEs have been used in biomedical settings. Specifically, we discuss their current applications and the improvements achieved in diagnostic and survival of patients. We focus on the applications in the field of RDs, and we discuss how the employment of AEs and VAEs would enhance RD understanding and diagnosis.

PMID:34639231 | PMC:PMC8509321 | DOI:10.3390/ijms221910891

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021 Oct 10;38(10):993-996. doi: 10.3760/cma.j.cn511374-20200408-00247.

ABSTRACT

OBJECTIVE: To investigate the genetic etiology, clinical diagnosis and treatment of a child with pancytopenia, failure to thrive and pulmonary infection.

METHODS: Peripheral blood samples of the child and her parents were collected. Genomic DNA was extracted. Genetic variants associated with hematological diseases were detected by high-throughput sequencing.

RESULTS: Three variants of TCN2 gene were found, one of which located in exon 5 upstream(c.581-8A>T), the parents has carried this variant; one in exon 6 (c.924_927del), the variant was originated from the mother; one in exon 7 (c.973C>T), the variant has ocurred de novo. The variants pathogenic analysis combined with clinical manifestation, pancytopenia, the increase in methylmalonic acid level and increased homocysteine, the child was diagnosed with transcobalaminIIdeficiency. The patient presented with respiratory infection, which was confirmed to be pneumocystosis by lung radioscopy and pathogenic high-throughput sequencing of broncho-alveolar lavage fluid. The patient presented with acute respiratory distress syndrome during the treatment with intramuscular injection of vitamin B12, and improved after anti-infection with compound sulfamethoxazole and symptomatic support treatment.

CONCLUSION: We reported a case of Chinese child with TCNII deficiency due to novel gene variant, and analyzed the pathogenicity of the three variants. The treatment of TCNII deficiency with cobalamin should be individualized.

PMID:34625940 | DOI:10.3760/cma.j.cn511374-20200408-00247

BMJ Case Rep. 2021 Oct 7;14(10):e244916. doi: 10.1136/bcr-2021-244916.

ABSTRACT

Wunderlich syndrome is a rare condition characterised by acute spontaneous non-traumatic renal haemorrhage into the subcapsular and perirenal spaces. Our case of anti-GAD65-associated autoimmune encephalitis (AE), aged 30 years, developed this complication following use of enoxaparin and was managed by selective glue embolisation of subsegmental branches of right renal cortical arteries. Our case had opsoclonus as one of the clinical manifestations, which has till now been described in only two patients of this AE. This patient received all forms of induction therapies (steroids, plasmapheresis, intravenous immunoglobulin and rituximab) following which she had good improvement in her clinical condition. The good response to immunotherapy is also a point of discussion as this has been rarely associated with anti-GAD65 AE.

PMID:34620636 | DOI:10.1136/bcr-2021-244916

Zhonghua Yu Fang Yi Xue Za Zhi. 2021 Sep 6;55(9):1023-1027. doi: 10.3760/cma.j.cn112150-20210427-00420.

ABSTRACT

Birth defects and rare diseases have become major public health problems, and early prevention and control are the most effective interventions. In recent years, with the rapid development of genomic techniques such as high-throughput sequencing, the level of screening and diagnosis of genetic birth defects and rare diseases has been greatly improved. This article reviews the application of genomic technologies in the pre-pregnancy, preimplantation, prenatal and neonatal stages, as well as the trend of clinical transformation, highlighting the broad prospects of constructing an early and precise prevention and control system in the era of genomic medicine.

PMID:34619916 | DOI:10.3760/cma.j.cn112150-20210427-00420

Eur Respir Rev. 2021 Oct 5;30(162):210078. doi: 10.1183/16000617.0078-2021. Print 2021 Dec 31.

ABSTRACT

OBJECTIVE: Immunoglobulin G4-related disease (IgG4-RD) is a rare orphan disease. Lung, pleura, pericardium, mediastinum, aorta and lymph node involvement has been reported with variable frequency and mostly in Asian studies. The objective of this study was to describe thoracic involvement assessed by high-resolution thoracic computed tomography (CT) in Caucasian patients with IgG4-RD.

METHODS: Thoracic CT scans before treatment were retrospectively collected through the French case registry of IgG4-RD and a single tertiary referral centre. CT scans were reviewed by two experts in thoracic imagery blinded from clinical data.

RESULTS: 48 IgG4-RD patients with thoracic involvement were analysed. All had American College of Rheumatology/European League Against Rheumatism classification scores ≥20 and comprehensive diagnostic criteria for IgG4-RD. CT scan findings showed heterogeneous lesions. Seven patterns were observed: peribronchovascular involvement (56%), lymph node enlargement (31%), nodular disease (25%), interstitial disease (25%), ground-glass opacities (10%), pleural disease (8%) and retromediastinal fibrosis (4%). In 37% of cases two or more patterns were associated. Asthma was significantly associated with peribronchovascular involvement (p=0.04). Among eight patients evaluated by CT scan before and after treatments, only two patients with interstitial disease displayed no improvement.

CONCLUSION: Thoracic involvement of IgG4-RD is heterogeneous and likely underestimated. The main thoracic CT scan patterns are peribronchovascular thickening and thoracic lymph nodes.

PMID:34615698 | DOI:10.1183/16000617.0078-2021

Dtsch Arztebl Int. 2021 Aug 9;118(31-32):538-539. doi: 10.3238/arztebl.m2021.0182.

NO ABSTRACT

PMID:34612193 | PMC:PMC8503947 | DOI:10.3238/arztebl.m2021.0182

J Control Release. 2021 Oct 1:S0168-3659(21)00526-5. doi: 10.1016/j.jconrel.2021.09.039. Online ahead of print.

ABSTRACT

Mutations in rhodopsin lead to its misfolding resulting in autosomal dominant retinitis pigmentosa (adRP). Pharmacological inhibition of the ATP-driven chaperone valosin-containing protein (VCP), a molecular checkpoint for protein quality control, slows down retinal degeneration in animal models. However, poor water-solubility of VCP inhibitors poses a challenge to their clinical translation as intravitreal injections for retinal treatment. In order to enable the delivery of VCP inhibitors, we have developed and investigated two formulations for the VCP inhibitor ML240. Nanoformulations of ML240 were obtained by using amphiphilic polymers methoxy-poly (ethylene glycol)5kDa-cholane (mPEG5kDa-cholane) and methoxy-poly (ethylene glycol)5kDa-cholesterol (mPEG5kDa-cholesterol). Both formulations increased the water-solubility of ML240 by two orders of magnitude and prolonged the drug released over ten days. In addition, encapsulation of ML240 in mPEG5kDa-cholane showed superior photoreceptor protection at lower drug concentrations, normalized rhodopsin localization, and alleviated inflammatory microglial responses in an ex vivo rat model of retinal degeneration. The study demonstrates the potential of VCP inhibitor nanoformulations to treat adRP, a pharmacologically orphan disease.

PMID:34606936 | DOI:10.1016/j.jconrel.2021.09.039

Orphanet J Rare Dis. 2021 Oct 2;16(1):408. doi: 10.1186/s13023-021-02047-1.

ABSTRACT

In 2001, Fondazione Telethon and the Italian muscular dystrophy patient organisation Unione Italiana Lotta alla Distrofia Muscolare joined their efforts to design and launch a call for grant applications specifically dedicated to clinical projects in the field of neuromuscular disorders. This strategic initiative, run regularly over the years and still ongoing, aims at supporting research with impact on the daily life of people with a neuromuscular condition and is centred on macro-priorities identified by the patient organisation. It is investigator-driven, and all proposals are peer-reviewed for quality and feasibility. Over the years, this funding program contributed to strengthening the activities of the Italian neuromuscular clinical network, reaching many achievements in healthcare research. Moreover, it has been an enabling factor for innovative therapy experimentation at international level and prepared the clinical ground to make therapies available to Italian patients. The ultimate scope of healthcare research is to ameliorate the delivery of care. In this paper, the achievements of the funded studies are analysed also from this viewpoint, to ascertain to which extent they have fulfilled the original goals established by the patient organisation. The evidence presented indicates that this has been a highly fruitful program. Factors that contributed to its success, lessons learned, challenges, and issues that remain to be addressed are discussed to provide practical examples of an experience that could inspire also other organizations active in the field of rare disease research.

PMID:34600567 | PMC:PMC8487484 | DOI:10.1186/s13023-021-02047-1

Orphanet J Rare Dis. 2021 Oct 2;16(1):407. doi: 10.1186/s13023-021-02030-w.

ABSTRACT

BACKGROUND: Mitochondrial diseases are difficult to diagnose and treat. Recent advances in genetic diagnostics and more effective treatment options can improve patient diagnosis and prognosis, but patients with mitochondrial disease typically experience delays in diagnosis and treatment. Here, we describe a unique collaborative practice model among physicians and scientists in Spain focused on identifying TK2 deficiency (TK2d), an ultra-rare mitochondrial DNA depletion and deletions syndrome.

MAIN BODY: This collaboration spans research and clinical care, including laboratory scientists, adult and pediatric neuromuscular clinicians, geneticists, and pathologists, and has resulted in diagnosis and consolidation of care for patients with TK2d. The incidence of TK2d is not known; however, the first clinical cases of TK2d were reported in 2001, and only ~ 107 unique cases had been reported as of 2018. This unique collaboration in Spain has led to the diagnosis of more than 30 patients with genetically confirmed TK2d across different regions of the country. Research affiliate centers have led investigative treatment with nucleosides based on understanding of TK2d clinical manifestations and disease mechanisms, which resulted in successful treatment of a TK2d mouse model with nucleotide therapy in 2010. Only 1 year later, this collaboration enabled rapid adoption of treatment with pyrimidine nucleotides (and later, nucleosides) under compassionate use. Success in TK2d diagnosis and treatment in Spain is attributable to two important factors: Spain's fully public national healthcare system, and the designation in 2015 of major National Reference Centers for Neuromuscular Disorders (CSURs). CSUR networking and dissemination facilitated development of a collaborative care network for TK2d disease, wherein participants share information and protocols to request approval from the Ministry of Health to initiate nucleoside therapy. Data have recently been collected in a retrospective study conducted under a Good Clinical Practice-compliant protocol to support development of a new therapeutic approach for TK2d, a progressive disease with no approved therapies.

CONCLUSIONS: The Spanish experience in diagnosis and treatment of TK2d is a model for the diagnosis and development of new treatments for very rare diseases within an existing healthcare system.

PMID:34600563 | PMC:PMC8487573 | DOI:10.1186/s13023-021-02030-w

Lancet Child Adolesc Health. 2021 Sep 29:S2352-4642(21)00245-5. doi: 10.1016/S2352-4642(21)00245-5. Online ahead of print.

ABSTRACT

BACKGROUND: Embryonal tumours with multi-layered rosettes (ETMRs) are a newly recognised, rare paediatric brain tumour with alterations of the C19MC microRNA locus. Due to varied diagnostic practices and scarce clinical data, disease features and determinants of outcomes for these tumours are poorly defined. We did an integrated clinicopathological and molecular analysis of primary ETMRs to define clinical phenotypes, and to identify prognostic factors of survival and key treatment modalities for this orphan disease.

METHODS: Paediatric patients with primary ETMRs and tissue available for analyses were identified from the Rare Brain Tumor Consortium global registry. The institutional histopathological diagnoses were centrally re-reviewed as per the current WHO CNS tumour guidelines, using histopathological and molecular assays. Only patients with complete clinical, treatment, and survival data on Nov 30, 2019, were included in clinicopathological analyses. Among patients who received primary multi-modal curative regimens, event-free survival and overall survival were determined using Cox proportional hazard and log-rank analyses. Univariate and multivariable Cox proportional hazard regression was used to estimate hazard ratios (HRs) with 95% CIs for clinical, molecular, or treatment-related prognostic factors.

FINDINGS: 159 patients had a confirmed molecular diagnosis of primary ETMRs (median age at diagnosis 26 months, IQR 18-36) and were included in our clinicopathological analysis. ETMRs were predominantly non-metastatic (94 [73%] of 128 patients), arising from multiple sites; 84 (55%) of 154 were cerebral tumours and 70 (45%) of 154 arose at sites characteristic of other brain tumours. Hallmark C19MC alterations were seen in 144 (91%) of 159 patients; 15 (9%) were ETMR not otherwise specified. In patients treated with curative intent, event-free survival was 57% (95% CI 47-68) at 6 months and 31% (21-42) at 2 years; overall survival was 29% (20-38) at 2 years and 27% (18-37) at 4 years. Overall survival was associated with non-metastatic disease (HR 0·48, 95% CI 0·28-0·80; p=0·0057) and non-brainstem location (0·42 [0·22-0·81]; p=0·013) on univariate analysis, as well as with gross total resection (0·30, 0·16-0·58; p=0·0014), high-dose chemotherapy (0·35, 0·19-0·67; p=0·0020), and radiotherapy (0·21, 0·10-0·41; p<0·0001) on multivariable analysis. 2-year event-free and overall survival was 0% at 2 years in patients treated with conventional chemotherapy without radiotherapy (regardless of surgery extent), and 21% (95% CI 1-41) and 30% (6-54), respectively, in patients treated with high-dose chemotherapy, and gross total resection without radiotherapy. 2-year event-free survival in patients treated with high-dose chemotherapy and radiotherapy was 66% (95% CI 39-93) for patients with gross total resection and 44% (7-81) for patients with sub-total resection. 2-5-year overall survival was 66% (95% CI 33-99, p=0·038) for patients with gross total resection and 67% (36-98, p=0·0020) for patients with sub-total resection.

INTERPRETATION: Prompt molecular diagnosis and post-surgical treatment with intensive multi-modal therapy tailored to patient-specific risk features could improve ETMR survival.

FUNDING: Canadian Institute of Health Research, Canada Research Chair Awards, Australian Lions Childhood Cancer Research Foundation, Spanish Society of Pediatrics, Consejería de Salud y Familias de la Junta de Andalucía, Miracle Marnie, Phoebe Rose Rocks, Tali's Funds, Garron Cancer Centre, Grace's Walk, Meagan's Hug, Brainchild, Nelina's Hope, and Jean Martel Foundation.

PMID:34599879 | DOI:10.1016/S2352-4642(21)00245-5

Acta Gastroenterol Belg. 2021 Jul-Sep;84(3):477-486. doi: 10.51821/84.3.013.

ABSTRACT

Benign recurrent intrahepatic cholestasis (BRIC) is a rare genetic disorder that is characterized by episodes of cholestasis followed by complete resolution. The episodic nature of BRIC raises concerns about its possible trigger factors. Indeed, case reports of this orphan disease have associated BRIC to some triggers. In the absence of any reviews, we reviewed BRIC trigger factors and its pathophysiology. The study consisted of a systematic search for case reports using PubMed. Articles describing a clear case of BRIC associated with a trigger were included resulting in 22 articles that describe 35 patients. Infection was responsible for 54.3% of triggered episodes, followed by hormonal, drugs, and miscellaneous causes reporting as 30%, 10%, and 5.7% respectively. Females predominated with 62.9%. The longest episode ranged between 3 months to 2 years with a mean of 32.37 weeks. The mean age of the first episode was 14.28 ranging between 3 months to 48 years. Winter and autumn were the major seasons during which episodes happened. Hence, BRIC is potentially triggered by infection, which is most commonly a viral infection, hormonal disturbances as seen in oral contraceptive pills and pregnancy state, and less commonly by certain drugs and other causes. The appearance of cholestasis during the first two trimesters of pregnancy compared to intrahepatic cholestasis of pregnancy could help to differentiate between the two conditions. The possible mechanism of BRIC induction implicates a role of BSEP and ATP8B1. While estrogen, drugs, and cytokines are known to affect BSEP, less is known about their action on ATP8B1.

PMID:34599573 | DOI:10.51821/84.3.013

Orphanet J Rare Dis. 2021 Sep 28;16(1):400. doi: 10.1186/s13023-021-02023-9.

ABSTRACT

BACKGROUND: During their studies, future physicians are often taught that while evaluating a patient they should first consider a common diagnosis and not a rare one. Consequently, although most physicians will face the diagnosis or treatment of a rare disease (RD) at some point in their professional lives, many assume that they might never meet a patient with a specific RD. Moreover, many physicians lack knowledge about RDs and are not prepared for caring for RD patients. Thus, the aim of this paper was to assess the awareness of RDs among Polish physicians.

METHODS: The study was conducted among 165 medical doctors taking their specialization courses at the Poznan University of Medical Sciences, Poland. The questionnaire assessed physicians' knowledge about the number, examples, etiology and estimated frequency of RDs. It also checked the self-assessment of physicians competence in RDs, as well as their opinions about university curricula in this respect.

RESULTS: The study shows that while most physicians lacked basic knowledge about the etiology, epidemiology and prevalence of RDs, many had also problems with separating RDs from more common disorders. Moreover, 94.6% of physicians perceived their knowledge on RDs as insufficient or very poor and less than 5% feel prepared for caring for patients with RDs. Simultaneously, while over 83% of physicians believed that RDs constitute a serious public health issue, 17% were of the opinion that mandatory courses on RDs are not necessary in medical curricula and 6.7% were not interested in broadening their knowledge of such diseases. Most respondents derived their knowledge on RDs from university courses, scientific literature and research, as well as from the Internet.

CONCLUSION: Since the study shows that there is a urgent need to fill the gap in physicians' knowledge on RDs, it seems advisable that extra courses on these diseases should be added to medical curricula and physicians' postgraduate training. Furthermore, as the Internet is the main source of information on RDs, e-learning programs and courses for all medical professionals should be organized.

PMID:34583737 | PMC:PMC8479904 | DOI:10.1186/s13023-021-02023-9

Orphanet J Rare Dis. 2021 Sep 28;16(1):402. doi: 10.1186/s13023-021-02046-2.

ABSTRACT

BACKGROUND: The diagnosis of the rare genetic diseases has great importance in treating multisystemic conditions, preventing potential complications, and estimating disease risk for family members. The duration of obtaining genetic test results is varies. The demand to learn the diagnosis of a possible untreatable illness involves a struggle between uncertainty and a lifetime chronic disease. The current uncertainty of their child's condition and the long wait for a diagnosis may increase the parents' anxiety level and cause difficulties in the continuation of diagnostic procedures in some families. This study aimed to investigate the prediagnosis and postdiagnosis anxiety levels of parents who have a child with a rare genetic disease.

METHOD: The parents in this study, mothers or fathers, admitted their children to the Bezmialem Vakıf University Medical Genetics Clinic due to a suspected rare genetic disease (n = 40). Researchers created "The Sociodemographic Questionnaire" and used it to analyze the parents' sociodemographic status. In addition, they used the State-Trait Anxiety Inventory (STAI) to determine the anxiety levels of the parents.

RESULTS: The state anxiety levels of parents decreased significantly after learning the diagnosis. However, there was no statistically significant decrease observed in trait anxiety levels.

CONCLUSION: Data from this study revealed that informing parents about their child's disease and properly explaining to them the expected difficulties might help to reduce their anxiety levels. Psychological support for parents is necessary to reduce their long-term stress, thus increasing the patient's compliance with treatment.

PMID:34583726 | PMC:PMC8480067 | DOI:10.1186/s13023-021-02046-2

Science. 2021 Sep 24;373(6562):1468-1473. doi: 10.1126/science.abi8206. Epub 2021 Sep 23.

ABSTRACT

[Figure: see text].

PMID:34554790 | DOI:10.1126/science.abi8206

Science. 2021 Sep 24;373(6562):1460-1463. doi: 10.1126/science.acx9135. Epub 2021 Sep 23.

ABSTRACT

[Figure: see text].

PMID:34554775 | DOI:10.1126/science.acx9135