European journal of medical genetics最新文献

{"title":"X-linked hypophosphatemia: The value of feedback focus groups to assess patient and caregiver needs","authors":"Estelle Wagner ,&nbsp;Aurélia Bertholet-Thomas ,&nbsp;Mélanie Romier ,&nbsp;Laure Loin ,&nbsp;Sandrine Lemoine ,&nbsp;Emmanuelle Vignot ,&nbsp;Sacha Flammier ,&nbsp;Charlotte Garnier ,&nbsp;Aurélie De-Mul ,&nbsp;Corinne Feutrier ,&nbsp;Sandrine Juillard ,&nbsp;Béatrice Thivichon-Prince ,&nbsp;Guillemette Lienhart ,&nbsp;Justine Bacchetta","doi":"10.1016/j.ejmg.2024.104912","DOIUrl":"10.1016/j.ejmg.2024.104912","url":null,"abstract":"<div><p>X-linked hypophosphatemia (XLH) is a rare, multi-systemic, invalidating disease requiring a multi-disciplinary approach. No specific action in XLH, neither for the patients’ specific needs nor for the methodology for the evaluation of these were found. Thus, to identify the needs of XLH patients and their caregivers, we organised focus groups in our reference centre with a view to build educational sessions. Focus groups including either XLH children, XLH adults, or caregivers ran in parallel. Each group was led by a person trained in therapeutic education (nurse, paediatric nephrologist) with another healthcare provider specialised in XLH (rheumatologist, nephrologist). One additional person with knowledge of XLH (clinical research associate, paediatric resident) took minutes. The duration of each session was 1.5h; XLH patients/caregivers were asked to answer age-adapted “open questions” on their daily life and quality of life. At the end, a global restitution was made. The needs identified were later grouped and analysed, which allowed us to build the educational sessions. The XLH children group included 5 children, the XLH adults group included 10 adults, and the caregivers group included 6 parents or partners. Major needs were identified: knowledge of XLH, treatment, dental care and adapted physical activity, with additional questions on socio-professional adaptations and financial support in adults. Partner patients were also identified to co-build the support programme. The study allowed us to identify the needs of XLH patients and their caregivers using the focus group method and then, using these needs, to build educational sessions and a therapeutic education programme for XLH patients.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"68 ","pages":"Article 104912"},"PeriodicalIF":1.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000041/pdfft?md5=2e180f5ebb9525df990153aaf2d3a0c3&pid=1-s2.0-S1769721224000041-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139678226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent MECR R258W causes adult-onset optic atrophy: A case report","authors":"Nan Jia ,&nbsp;Shuiqing Yu ,&nbsp;Geng Zhang ,&nbsp;Lin Li ,&nbsp;Jiawei Wang ,&nbsp;Chuntao Lai","doi":"10.1016/j.ejmg.2024.104917","DOIUrl":"10.1016/j.ejmg.2024.104917","url":null,"abstract":"<div><p><em>MECR</em>-related neurologic disorder, also known as mitochondrial enoyl CoA reductase protein-associated neurodegeneration (MEPAN) or dystonia with optic atrophy and basal ganglia abnormalities in childhood (MIM: #<span>617282</span><svg><path></path></svg>), is an autosomal recessive inherited disease characterized by a progressive childhood-onset movement disorder and optic atrophy. Here we report a 19-year-old male, presented with progressive visual failure, nystagmus, and right orbital pain, with no history of movement or eye disorder in his childhood. His visual decline started at age 18 years, whereas nystagmus emerged seven months later. Analysis of whole-exome sequencing (WES) revealed a homozygous recurrent variant (NM_016011.5:c.772C &gt; T, p.Arg258Trp) in <em>MECR</em>. These findings suggest phenotypic heterogeneity in <em>MECR</em>-related neurologic disorder, thus, more relevant case screening, will help to delineate the genotype-phenotype correlation of the <em>MECR</em> gene.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"68 ","pages":"Article 104917"},"PeriodicalIF":1.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000090/pdfft?md5=9ac0160ba080e6cc3ab4fad0502c3134&pid=1-s2.0-S1769721224000090-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139656223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ERN BOND: The key European network leveraging diagnosis, research, and treatment for rare bone conditions","authors":"Lorena Casareto ,&nbsp;Natasha M. Appelman-Dijkstra ,&nbsp;Maria Luisa Brandi ,&nbsp;Roland Chapurlat ,&nbsp;Valérie Cormier-Daire ,&nbsp;Neveen A.T. Hamdy ,&nbsp;Karen E. Heath ,&nbsp;Joachim Horn ,&nbsp;Giovanna Mantovani ,&nbsp;Klaus Mohnike ,&nbsp;Sérgio Bernardo Sousa ,&nbsp;André Travessa ,&nbsp;Lena Lande Wekre ,&nbsp;M. Carola Zillikens ,&nbsp;Luca Sangiorgi ,&nbsp;the European Reference Network on rare BONe Diseases","doi":"10.1016/j.ejmg.2024.104916","DOIUrl":"10.1016/j.ejmg.2024.104916","url":null,"abstract":"<div><p>There is no universally accepted definition for rare diseases: in Europe a disease is considered to be rare when affecting fewer than 1 in 2000 people. European Reference Networks (ERNs) have been the concrete response to address the unmet needs of rare disease patients and many pan-European issues in the field, reducing inequities, and significantly increasing accessibility to high-quality healthcare across Europe. ERNs are virtual networks, involving centres and patient representatives with the general scope to facilitate discussion on complex cases requiring highly specialised competences and trained expertise. ERN BOND - the European Reference Network on rare BONe Diseases - is one of these 24 approved networks with the specific ongoing mission to implement measures facilitating multidisciplinary, holistic, continuous, patient-centred, and participative care provision to patients, and supporting them in the full realisation of their fundamental human rights. ERN BOND includes in 2023 a total of 53 centres of expertise from 20 European countries. Its governing structure installed in March 2017 includes decision-making, operative and consultative committees, which comprise experts in the field and patient representatives ensuring patient's voice and perspectives are taken into account.</p><p>Over the years, ERN BOND has worked hard to achieve its mission and valuably contribute to the advancement of diagnosis, management, treatment, and research in rare diseases. The network activities are mainly related to (i) the provision of care which collectively involves averagely 2800 patients diagnosed per year, (ii) the development of education for and training of the healthcare personnel consisting until now in the realisation of 7 thematic workshops and 19 webinars, (iii) the dissemination and exchange and spread of knowledge via network's website (<span>https://ernbond.eu/</span><svg><path></path></svg>), social media channels, and newsletters, (iv) the management of related data through a disease registry currently mapping over 2300 cases and recording over 600 reported cases, and (v) the enhancement of research which now include two clinical trials endorsed by the network.</p><p>ERN BOND represents therefore an unprecedented move to improve the healthcare management of patients suffering from rare bone diseases through European collaborations. This network, through the support from the European Health Programme, will continue to pursue its efforts to achieve its goals, always maintaining the patients and their families at the centre of healthcare services.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"68 ","pages":"Article 104916"},"PeriodicalIF":1.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000089/pdfft?md5=bdd64342eac2ae392579bbf941696046&pid=1-s2.0-S1769721224000089-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139656225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pachydysostosis of the fibula in a case of familial adenomatous polyposis","authors":"Daniela Oliveira ,&nbsp;Sofia Maia ,&nbsp;Inês Balacó ,&nbsp;Paulo Coelho ,&nbsp;Susana Almeida ,&nbsp;Margarida Venâncio ,&nbsp;Jorge Saraiva ,&nbsp;Gen Nishimura ,&nbsp;Sérgio B. Sousa","doi":"10.1016/j.ejmg.2024.104913","DOIUrl":"10.1016/j.ejmg.2024.104913","url":null,"abstract":"<div><h3>Background</h3><p>Familial Adenomatous Polyposis (FAP) is a colorectal cancer (CRC) predisposition syndrome caused by germline <em>APC</em> mutations and characterised by an increased risk of CRC and colonic polyps and, in certain forms, of specific prominent extraintestinal manifestations, namely osteomas, soft tissue tumours and dental anomalies. Pachydysostosis of the fibula is a rare clinical entity defined by unilateral bowing of the distal portion of the fibula and elongation of the entire bone, without affectation of the tibia.</p></div><div><h3>Clinical report</h3><p>We report a 17-year-old male, who presented with a non-progressive bowing of the right leg detected at 18 months of age caused by a fibula malformation (later characterized as pachydysostosis) and a large exophytic osteoma of the left radius, noticed at the age of 15 years, without gastrointestinal symptoms. There was no relevant family history. Detailed characterisation revealed multiple osteomas, skin lesions and dental abnormalities, raising the hypothesis of FAP. This diagnosis was confirmed by genetic testing [c.4406_4409dup p.(Ala1471Serfs*17) <em>de novo</em> mutation in the <em>APC</em> gene] and endoscopic investigation (multiple adenomas throughout the colon, ileum and stomach).</p></div><div><h3>Discussion</h3><p>This case report draws attention to the phenotypic spectrum of skeletal manifestations of FAP: this patient has a congenital fibula malformation, not previously associated with this syndrome, but which is likely to have been its first manifestation in this patient. This clinical case also illustrates the challenges in the early diagnosis of FAP, especially without family history, and highlights the importance of a multidisciplinary approach and the adequate study of rare skeletal abnormalities.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"68 ","pages":"Article 104913"},"PeriodicalIF":1.9,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000053/pdfft?md5=9c60e2878b352d1fbe7b554979755de8&pid=1-s2.0-S1769721224000053-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139575394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A spectrum of TP63-related disorders with eight affected individuals in five unrelated families","authors":"Merve Soğukpınar,&nbsp;Gülen Eda Utine,&nbsp;Koray Boduroğlu,&nbsp;Pelin Özlem Şimşek-Kiper","doi":"10.1016/j.ejmg.2024.104911","DOIUrl":"10.1016/j.ejmg.2024.104911","url":null,"abstract":"<div><p><em>TP63</em>-related disdorders broadly involve varying combinations of ectodermal dysplasia (sparse hair, hypohydrosis, tooth abnormalities, nail dysplasia), cleft lip/palate, acromelic malformation, split-hand/foot malformation/syndactyly, ankyloblepharon filiforme adnatum, lacrimal duct obstruction, hypopigmentation, and hypoplastic breasts and/or nipples. <em>TP63</em>-related disorders are associated with heterozygous pathogenic variants in <em>TP63</em> and include seven overlapping phenotypes; Ankyloblepharon‐ectodermal defects‐cleft lip/palate syndrome (AEC), Ectrodactyly‐ectodermal dysplasia‐cleft lip/palate syndrome 3 (EEC3), Limb‐mammary syndrome (LMS), Acro‐dermo‐ungual‐lacrimal‐tooth syndrome (ADULT), Rapp–Hodgkin syndrome (RHS), Split-hand/foot malformation 4 (SHFM4), and Orofacial cleft 8. We report on five unrelated families with 8 affected individuals in which the probands presented with varying combinations of ectodermal dysplasia, cleft lip/palate, split-hand/foot malformation, lacrimal duct obstruction, and ankyloblepharon filiforme adnatum. The clinical diagnosis involved AEC syndrome (2 patients), EEC3 syndrome (2 patients), and a yet hitherto unclassified <em>TP63</em>-related disorder. Sanger sequence analysis of the <em>TP63</em> gene was performed revealing five different variants among which four were novel and three were <em>de novo.</em> The identificated <em>TP63</em> variants co-segregated with the other affected individuals in the families. The abnormalities of ectoderm derived structures including hair, nails, sweat glands, and teeth should alert the physician to the possibility of <em>TP63</em>-related disorders particularly in the presence of orofacial clefting.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"68 ","pages":"Article 104911"},"PeriodicalIF":1.9,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S176972122400003X/pdfft?md5=1b05fa487a519837a704213e6b552006&pid=1-s2.0-S176972122400003X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lenz-Majewski syndrome and recurrent otitis media: Are they related or not?","authors":"Fayize Maden Bedel ,&nbsp;Özgür Balasar ,&nbsp;Selma Erol Aytekin ,&nbsp;Sevgi Keleş ,&nbsp;Hüseyin Çaksen","doi":"10.1016/j.ejmg.2024.104910","DOIUrl":"10.1016/j.ejmg.2024.104910","url":null,"abstract":"<div><p>Lenz-Majewski hyperostotic dwarfism (LMHD) is a rare condition characterized by intellectual disability, sclerosing bone dysplasia, dysmorphic facial features, brachydactyly, symphalangism and cutis laxa. Nineteen cases have been reported in the literature so far, eleven of them with PTDSS1 mutations. Although studies have had clinically similar findings, in some cases the authors have reported even rarer features such as hydrocephalus, facial paralysis, and cleft palate. We, hereby, report the case of the first patient with Lenz-Majewski syndrome (LMS) with molecular confirmation from Turkey. Although our patient had characteristic features described in the literature, she also had immunodeficiency, which has not been reported before. Although there is no established phenotype-genotype correlation, molecular mechanisms can be explained with the reporting of more patients.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"68 ","pages":"Article 104910"},"PeriodicalIF":1.9,"publicationDate":"2024-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000028/pdfft?md5=49b8a7221ddf184aa42f6309d71eec82&pid=1-s2.0-S1769721224000028-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139516355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating ClinGen variant curation expert panels' application of PVS1 code","authors":"Xiaoyan Wang ,&nbsp;Haibo Li ,&nbsp;Haiyan Luo ,&nbsp;Yongyi Zou ,&nbsp;Haoxian Li ,&nbsp;Yayun Qin ,&nbsp;Jieping Song","doi":"10.1016/j.ejmg.2024.104909","DOIUrl":"10.1016/j.ejmg.2024.104909","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;The 2015 American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) guidelines articulates that the effects of certain types of variants on gene function can often be seen as a complete absence of the gene product by leading to a lack of transcription or nonsense-mediated decay(NMD). However, detailed information considering different types of loss of function(LOF) variants, refined steps assimilating details concerning location of variant, changes in strength levels, NMD boundary, or any additional information pointing to a true null effect, were all left to expert judgement. As part of its Clinical Genome Resource (ClinGen) initiative, Variant Curation Expert Panels (VCEPs) are designated to make gene/disease-centric specifications in accordance with the ACMG/AMP guidelines, including a more detailed definition of what constitutes an appropriate LOF evidence. Our goal was to evaluate the current LOF guidelines developed by the VCEPs and analyse the prior curated variants concerning the PVS1 criteria, bringing people occupied in genetic data analysis a comprehensive understanding of this code.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;Our study evaluated 7 VCEPs for their LOF criteria (PVS1). Subsequently, we assessed the predictive criteria by considering the underlying disease mechanism, protein transcript, and variant types delineated. Then, we meticulously curated the LOF evidence referenced by each VCEP in their preliminary variant classification, thereby scrutinizing the recommendations put forth by VCEPs and their application in the interpretation of the aforementioned predictive criteria. Based on these, an extensive curation of evidence summary considering PVS1 applied by VCEPs according to their classification of pilot variants for the purpose of analyzing VCEP criteria specifications and their use in the understanding of LOF was conducted.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;We observed in this article that the VCEPs discussed followed the majority of Sequence Variant Interpretation (SVI) recommendations concerning the application of this LOF criteria, except for some disease/gene specific considerations. We highlighted the wide range of PVS1 strength levels approved by VCEP, reflecting the diversity of evidence for each variants type. In addition, we observed substantial differences in the approach used to determine relative strengths for different types of null variants and in the attitude towards these principles concerning variant location, NMD and influence to protein function between VCEPs.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;It is difficult to understand the intricacies of the predictive data(PVS1), which often requires expert-level knowledge of disease/gene. The VCEP criteria specifications for the predictive evidence play an important role in making it more accessible for the curators to apply the predictive data by providing details concerning this complex criteria.","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"67 ","pages":"Article 104909"},"PeriodicalIF":1.9,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000016/pdfft?md5=073ce930fed3d21be8e878635cf9bc57&pid=1-s2.0-S1769721224000016-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139398026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The VASCERN PPL working group patient pathway for primary and paediatric lymphoedema","authors":"Nele Devoogdt ,&nbsp;Sarah Thomis ,&nbsp;Florence Belva ,&nbsp;Janine Dickinson-Blok ,&nbsp;Caroline Fourgeaud ,&nbsp;Guido Giacalone ,&nbsp;Tonny Karlsmark ,&nbsp;Heli Kavola ,&nbsp;Vaughan Keeley ,&nbsp;Manuela Lourenço Marques ,&nbsp;Sahar Mansour ,&nbsp;Christoffer V. Nissen ,&nbsp;Susan Nørregaard ,&nbsp;Michael Oberlin ,&nbsp;Tanja Planinšek Ručigaj ,&nbsp;Gloria Somalo-Barranco ,&nbsp;Sinikka Suominen ,&nbsp;Kirsten Van Duinen ,&nbsp;Stéphane Vignes ,&nbsp;Robert Damstra","doi":"10.1016/j.ejmg.2023.104905","DOIUrl":"10.1016/j.ejmg.2023.104905","url":null,"abstract":"<div><p>Lymphoedema is caused by an imbalance between fluid production and transport by the lymphatic system. This imbalance can be either caused by reduced transport capacity of the lymphatic system or too much fluid production and leads to swelling associated with tissue changes (skin thickening, fat deposition). Its main common complication is the increased risk of developing cellulitis/erysipelas in the affected area, which can worsen the lymphatic function and can be the cause of raised morbidity of the patient if not treated correctly/urgently. The term primary lymphoedema covers a group of rare conditions caused by abnormal functioning and/or development of the lymphatic system. It covers a highly heterogeneous group of conditions. An accurate diagnosis of primary lymphoedema is crucial for the implementation of an optimal treatment plan and management, as well as to reduce the risk of worsening. Patient care is diverse across Europe, and national specialised centres and networks are not available everywhere. The European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN) gathers the best expertise in Europe and provide accessible cross-border healthcare to patients with rare vascular diseases. There are six different working groups in VASCERN, which focus on arterial diseases, hereditary haemorrhagic telangiectasia, neurovascular diseases, lymphoedema and vascular anomalies. The working group Paediatric and Primary Lymphedema (PPL WG) gathers and shares knowledge and expertise in the diagnosis and management of adults and children with primary and paediatric lymphoedema. The members of PPL WG have worked together to produce this opinion statement reflecting strategies on how to approach patients with primary and paediatric lymphoedema. The objective of this patient pathway is to improve patient care by reducing the time to diagnosis, define the best management and follow-up strategies and avoid overuse of resources. Therefore, the patient pathway describes the clinical evaluation and investigations that lead to a clinical diagnosis, the genetic testing, differential diagnosis, the management and treatment options and the patient follow up at expert and local centres. Also, the importance of the patient group participation in the PPL WG is discussed.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"67 ","pages":"Article 104905"},"PeriodicalIF":1.9,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721223002112/pdfft?md5=26bf0e7644055740993c78cb96f919da&pid=1-s2.0-S1769721223002112-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139018013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathological mandibular fracture complicated by osteonecrosis in an adult patient with pycnodysostosis: clinical report and review of the literature","authors":"Alice Moroni ,&nbsp;Evelise Brizola ,&nbsp;Alessia Di Cecco ,&nbsp;Morena Tremosini ,&nbsp;Marta Sergiampietri ,&nbsp;Alberto Bianchi ,&nbsp;Barbara Tappino ,&nbsp;Maria Piana ,&nbsp;Maria Gnoli","doi":"10.1016/j.ejmg.2023.104904","DOIUrl":"10.1016/j.ejmg.2023.104904","url":null,"abstract":"<div><p>Pycnodysostosis is an ultra-rare osteosclerotic skeletal disorder characterized by short stature, susceptibly to fractures, acroosteolysis of the distal phalanges, and craniofacial features (frontal bossing, prominent nose, obtuse mandibular angle, micrognathia). Dental abnormalities (delayed eruption of teeth, hypodontia, malocclusion, dental crowding, persistence of deciduous teeth, enamel hypoplasia, and increased caries) are also frequent; due to bone metabolism alteration, the patients have an increased risk for jaw osteomyelitis, especially after tooth extraction or mandible fracture. Other complications are obstructive sleep apnea, endocrine alterations and cytopenia. Pycnodysostosis is caused by biallelic loss of function variants in <em>CTSK</em> gene, coding the lysosomal protease cathepsin K. CTSK is involved in the degradation of bone matrix proteins, such as type I and type II collagen. In pycnodysostosis, this degradation is decreased, leading to increased bone density and bone fragility with pathological fractures and poor healing.</p><p>We present a clinical report of a female adult patient with typical pycnodysostosis phenotype. At the age of 52 years, she had a pathological spontaneous fracture of the right mandible complicated by osteonecrosis, treated with load bearing osteosynthesis. The direct sequencing of <em>CTSK</em> gene revealed the presence of the pathogenic homozygous variant c.746T&gt;A, (p.Ile249Asn), that confirmed the diagnosis of pycnodysostosis.</p><p>We also review the literature case series published to date, that suggest to always consider the diagnosis of pycnodysostosis in case of osteosclerosis, even in the absence of brachydactyly or short stature.</p><p>This report details the natural history of the disease in this patient, from childhood to adulthood, and highlights the importance of a quality of life assessment. In addition, we describe a case of mandibular osteonecrosis and spontaneous fracture in pycnodysostosis, drawing attention on the maxillofacial complications in these patients and on the importance of a personalized follow-up.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"67 ","pages":"Article 104904"},"PeriodicalIF":1.9,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721223002100/pdfft?md5=4931d6fea0917ee049aae0c1b766e538&pid=1-s2.0-S1769721223002100-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139024693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic counselling supervision: Luxury or necessity? A qualitative study with genetic healthcare professionals in Portugal","authors":"Lídia Guimarães ,&nbsp;Ruxanda Baião ,&nbsp;Catarina Costa ,&nbsp;Marina Lemos ,&nbsp;Margarida Rangel Henriques ,&nbsp;Milena Paneque","doi":"10.1016/j.ejmg.2023.104908","DOIUrl":"10.1016/j.ejmg.2023.104908","url":null,"abstract":"<div><p>In recent years, there has been a significant technological evolution in the field of genetics, leading to an increase in the number of professionals working in medical genetics and, consequently, a tremendous growth in genetic counselling. At the same time, there has been a growing recognition of the parameters on which to base a safe practice, not only regarding the technical skills of the professional but also regarding their counselling skills, including relational and empathy skills and the acknowledgement of the emotional impact that genetic counselling practice can have. However, despite this growing knowledge, there are still significant differences between the various European countries, and one area where this discrepancy is particularly evident is genetic counselling supervision. Thus, if there are countries where genetic counselling supervision is not even known by the professionals, there are others where it is mandatory for practice. This research had as an objective to understand if and how genetic counselling supervision is provided in Portugal, to identify routines, challenges and impacts of genetic counselling that should be explored in a supervision process and comprehend how professionals believe supervision should be conducted to be effective. A total of sixteen medical geneticists from main Portuguese genetic services were present in two online focus groups. None of the participants had access to genetic counselling supervision as a programmed routine and there was a consensus that a service of this kind would be particularly important for the professionals as genetic counselling has frequently challenging and emotional moments. Aspects regarding clinical supervision, the characteristics of the supervisor and the practical aspects of genetic counselling supervision implementation were also mentioned during the discussions. These results highlight the relevancy of the establishment of GC supervision routines and standardized guidelines in our country, as well as a need for evidence-based research focused on its impact at professional and practice level.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"67 ","pages":"Article 104908"},"PeriodicalIF":1.9,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721223002148/pdfft?md5=1f08425c6556ac7b74ad673a8246d504&pid=1-s2.0-S1769721223002148-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139017868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}