European journal of medical genetics最新文献

{"title":"Beyond 'speech delay': Expanding the phenotype of BRPF1-related disorder","authors":"Lottie D. Morison ,&nbsp;Olivia Van Reyk ,&nbsp;Emma Baker ,&nbsp;Lyse Ruaud ,&nbsp;Nathalie Couque ,&nbsp;Alain Verloes ,&nbsp;David J. Amor ,&nbsp;Angela T. Morgan","doi":"10.1016/j.ejmg.2024.104923","DOIUrl":"10.1016/j.ejmg.2024.104923","url":null,"abstract":"<div><p>Pathogenic variants in <em>BRPF1</em> cause intellectual disability, ptosis and facial dysmorphism. Speech and language deficits have been identified as a manifestation of <em>BRPF1-</em>related disorder but have not been systematically characterized. We provide a comprehensive delineation of speech and language abilities in <em>BRPF1</em>-related disorder and expand the phenotype. Speech and language, and health and medical history were assessed in 15 participants (male = 10, median age = 7 years 4 months) with 14 <em>BRPF1</em> variants. Language disorders were common (11/12), and most had mild to moderate deficits across receptive, expressive, written, and social-pragmatic domains. Speech disorders were frequent (7/9), including phonological delay (6/9) and disorder (3/9), and childhood apraxia of speech (3/9). All those tested for cognitive abilities had a FSIQ ≥70 (4/4). Participants had vision impairment (13/15), fine (8/15) and gross motor delay (10/15) which often resolved in later childhood, infant feeding impairment (8/15), and infant hypotonia (9/15). We have implicated <em>BRPF1-</em>related disorder as causative for speech and language disorder, including childhood apraxia of speech. Adaptive behavior and cognition were strengths when compared to other monogenic neurodevelopmental chromatin-related disorders. The universal involvement of speech and language impairment is noteable, relative to the high degree of phenotypic variability in <em>BRPF1-</em>related disorder.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"68 ","pages":"Article 104923"},"PeriodicalIF":1.9,"publicationDate":"2024-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000156/pdfft?md5=381f1a56300a0473ef2d84a5ba13915a&pid=1-s2.0-S1769721224000156-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722164","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":"TBX5 variants and cardiac phenotype: A systematic review of the literature and a novel variant","authors":"Anne Kathrine Møller Nielsen ,&nbsp;Anna Maria Dehn ,&nbsp;Vibeke Hjortdal ,&nbsp;Lars Allan Larsen","doi":"10.1016/j.ejmg.2024.104920","DOIUrl":"10.1016/j.ejmg.2024.104920","url":null,"abstract":"<div><p>T-Box Transcription Factor 5 (<em>TBX5</em>) variants are associated with Holt-Oram syndrome. Holt-Oram syndrome display phenotypic variability, regarding upper limb defects, congenital heart defects, and arrhythmias. To investigate the genotype-phenotype relationship between <em>TBX5</em> variants and cardiac disease, we performed a systematic review of the literature. Through the systematic review we identified 108 variants in <em>TBX5</em> associated with a cardiac phenotype in 277 patients. Arrhythmias were more frequent in patients with a missense variant (48% vs 30%, p = 0.009) and upper limb abnormalities were more frequent in patients with protein-truncating variants (85% vs 64%, p = 0.0008). We found clustering of missense variants in the T-box domain. Furthermore, we present a family with atrial septal defects. By whole exome sequencing, we identified a novel missense variant p.Phe232Leu in <em>TBX5</em>. The cardiac phenotype included atrial septal defect, arrhythmias, heart failure, and dilated cardiomyopathy. Clinical examination revealed subtle upper limb abnormalities. Thus, the family corresponds to the diagnostic criteria of Holt-Oram syndrome.</p><p>We provide an overview of cardiac phenotypes associated with <em>TBX5</em> variants and show an increased risk of arrhythmias associated to missense variants compared to protein-truncating variants. We report a novel missense variant in <em>TBX5</em> in a family with an atypical Holt-Oram syndrome phenotype.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"68 ","pages":"Article 104920"},"PeriodicalIF":1.9,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000120/pdfft?md5=79fb65ff0aca33731b5306bf7153af79&pid=1-s2.0-S1769721224000120-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139711795","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":"Altered peripheral blood leukocyte subpopulations, function, and gene expression in children with Down syndrome: implications for respiratory tract infection","authors":"Kelley L. Colvin ,&nbsp;Kristine Wolter-Warmerdam ,&nbsp;Francis Hickey ,&nbsp;Michael E. Yeager","doi":"10.1016/j.ejmg.2024.104922","DOIUrl":"10.1016/j.ejmg.2024.104922","url":null,"abstract":"<div><h3>Objectives</h3><p>We tested the hypothesis that aberrant expression of Hsa21-encoded interferon genes in peripheral blood immune cells would correlate to immune cell dysfunction in children with Down syndrome (DS).</p></div><div><h3>Study design</h3><p>We performed flow cytometry to quantify peripheral blood leukocyte subtypes and measured their ability to migrate and phagocytose. In matched samples, we measured gene expression levels for constituents of interferon signaling pathways. We screened 49 children, of which 29 were individuals with DS.</p></div><div><h3>Results</h3><p>We show that the percentages of two peripheral blood myeloid cell subtypes (alternatively-activated macrophages and low-density granulocytes) in children with DS differed significantly from typical children, children with DS circulate a very different pattern of cytokines vs. typical individuals, and higher expression levels of type III interferon receptor Interleukin-10Rb in individuals with DS correlated with reduced migratory and phagocytic capacity of macrophages.</p></div><div><h3>Conclusions</h3><p>Increased susceptibility to severe and chronic infection in children with DS may result from inappropriate numbers and subtypes of immune cells that are phenotypically and functionally altered due to trisomy 21 associated interferonopathy.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"68 ","pages":"Article 104922"},"PeriodicalIF":1.9,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000144/pdfft?md5=8736f775e4024936e7613a8fe394e4ba&pid=1-s2.0-S1769721224000144-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139690168","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":"Rapid exome sequencing for children with severe acute encephalopathy – A case series","authors":"Clair Habib ,&nbsp;Tamar Paperna ,&nbsp;Rinat Zaid ,&nbsp;Sarit Ravid ,&nbsp;Josef Ben Ari ,&nbsp;Galit Tal ,&nbsp;Karin Weiss ,&nbsp;Tova Hershkovitz","doi":"10.1016/j.ejmg.2024.104918","DOIUrl":"10.1016/j.ejmg.2024.104918","url":null,"abstract":"<div><p>Increasingly, next-generation sequencing (NGS) is becoming an invaluable tool in the diagnosis of unexplained acute neurological disorders, such as acute encephalopathy/encephalitis. Here, we describe a brief series of pediatric patients who presented at the pediatric intensive care unit with severe acute encephalopathy, initially suspected as infectious or inflammatory but subsequently diagnosed with a monogenic disorder.</p><p>Rapid exome sequencing was performed during the initial hospitalization of three unrelated patients, and results were delivered within 7–21 days. All patients were previously healthy, 1.5–3 years old, of Muslim Arab descent, with consanguineous parents. One patient presenting with acute necrotizing encephalopathy (ANEC). Her sister presented with ANEC one year prior.</p><p>Exome sequencing was diagnostic in all three patients. All were homozygous for pathogenic and likely-pathogenic variants associated with recessive disorders; MOCS2, NDUFS8 and DBR1. Surprisingly, the initial workup was not suggestive of the final diagnosis.</p><p>This case series demonstrates that the use of rapid exome sequencing is shifting the paradigm of diagnostics even in critical care situations and should be considered early on in children with acute encephalopathy. A timely diagnosis can direct initial treatment as well as inform decisions regarding long-term care.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"68 ","pages":"Article 104918"},"PeriodicalIF":1.9,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000107/pdfft?md5=4817e4a68c204c7ffedb6884840898f8&pid=1-s2.0-S1769721224000107-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702181","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":"Impressive clinical improvement and disappearance of neuropathic pain in an adult patient with hypophosphatasia treated with asfotase alfa","authors":"Zografia Zervou ,&nbsp;Roel Plooij ,&nbsp;Evert F.S. van Velsen ,&nbsp;Remco G.M. Timmermans ,&nbsp;Serwet Demirdas ,&nbsp;M. Carola Zillikens","doi":"10.1016/j.ejmg.2024.104915","DOIUrl":"10.1016/j.ejmg.2024.104915","url":null,"abstract":"<div><p>Hypophosphatasia (HPP) is a rare disorder, resulting from loss-of-function variants of the ALPL gene encoding non-tissue specific alkaline phosphatase (TNSALP). Presentation varies largely, with increased severity usually occurring with earlier disease onset. Here we describe the clinical improvement of a 57-year-old woman with childhood onset HPP, after initiating treatment with asfotase alfa (Strensiq®). This was started because of the rapid and progressive radiological deterioration of bone structure after placement of nails in both upper legs for spontaneous atypical femur fracture (AFF) - like fractures. Initiation of treatment, not only resulted in stabilization of bone structure on X-rays, but within a few weeks there was a dramatic reduction of burning pain sensations in the lower legs, attributed in retrospect to neuropathic pain, and also almost complete disappearance of headaches. Additionally, unhealed metatarsal fractures finally healed after almost 10 years. Drug efficacy was further evaluated through -quality of life questionnaires and multiple tests conducted by the physiotherapist, and showed clear improvements. Within 3 months after starting asfotase alfa, the patient was able to carry out her daily tasks indoors without relying on a walker and even started electric bike rides for 20 km/day. In conclusion, treatment with asfotase alfa, halted rapid radiological bone deterioration after bilateral intramedullary femoral pen placement and strongly increased quality of life, marked by rapid disappearance of neuropathic pain, reduction in headaches and musculoskeletal pains, and enhanced muscle strength and mobility. The quick and almost complete disappearance of neuropathic pain and headache suggests a relation with disturbed levels of metabolites in HPP.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"68 ","pages":"Article 104915"},"PeriodicalIF":1.9,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000077/pdfft?md5=f9ca4ebb87cb392455bfab7eb6de6900&pid=1-s2.0-S1769721224000077-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702180","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":"Development of a low-cost and accurate carrier screening method for spinal muscular atrophy in developing countries","authors":"Yu Jiang ,&nbsp;Zhenyu Luo ,&nbsp;Wenrong Wang ,&nbsp;Xingxiu Lu ,&nbsp;ZhongMin Xia ,&nbsp;Jieqiong Xie ,&nbsp;Mei Lu ,&nbsp;Lili Wu ,&nbsp;Yulin Zhou ,&nbsp;Qiwei Guo","doi":"10.1016/j.ejmg.2024.104921","DOIUrl":"10.1016/j.ejmg.2024.104921","url":null,"abstract":"<div><p>Heterozygous carriers of the survival of motor neuron 1 (<em>SMN1</em>) gene deletion in parents account for approximately 95% of neonatal spinal muscular atrophy cases. Given the severity of the disease, professional organizations have recommended periconceptional spinal muscular atrophy carrier screening to all couples, regardless of race or ethnicity. However, the prevalence of screening activities in mainland China remains suboptimal, mainly attributed to the limitations of the existing carrier screening methods. Herein, we aimed to develop a low-cost, accessible, and accurate carrier screening method based on duplex droplet digital PCR (ddPCR), to cover a wider population in developing countries, including China. The receiver operating characteristic curve was used to determine the cut-off value of <em>SMN1</em> copy numbers. Performance validation was conducted for linearity, precision, and accuracy. In total, 482 cases were considered to validate the concordance between the developed ddPCR assay and multiplex ligation-dependent probe amplification. Linear correlations were excellent between the expected concentration of the reference gene and the observed values (R² &gt; 0.99). Both the intra- and inter-assay precision of our ddPCR assays were less than 6.0%. The multiplex ligation-dependent probe amplification and ddPCR results were consistent in 480 of the 482 cases (99.6%). Two cases with multiplex ligation-dependent probe amplification, suggestive of two copies of <em>SMN1</em> exon 7, were classified into three copies by ddPCR analysis. The overall correct classification of the samples included in our ddPCR assay was 100%. This study demonstrates that an appropriate cut-off value is an important prerequisite for establishing a semi-quantitative method to determine the <em>SMN1</em> copy numbers. Compared to conventional methods, our ddPCR assay is low-cost, highly accurate, and has full potential for application in population spinal muscular atrophy carriers screening.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"68 ","pages":"Article 104921"},"PeriodicalIF":1.9,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000132/pdfft?md5=cfd4db4d64b8ec77a305d5a9bb260c49&pid=1-s2.0-S1769721224000132-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702179","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":"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}