European journal of medical genetics最新文献

{"title":"The first Brazilian clinical report of Kleefstra syndrome, including semicircular canals agenesis as a possible phenotype expansion","authors":"Eduardo Da Cás ,&nbsp;Lucas V.L. Pires ,&nbsp;Bianca D.W. Linnenkamp ,&nbsp;Marcella C. Allegro ,&nbsp;Rachel S. Honjo ,&nbsp;Débora R. Bertola ,&nbsp;Hiromi Aoi ,&nbsp;Naomichi Matsumoto ,&nbsp;Chong Ae Kim","doi":"10.1016/j.ejmg.2024.104966","DOIUrl":"10.1016/j.ejmg.2024.104966","url":null,"abstract":"<div><h3>Objective</h3><p>to report the first case series of Brazilian children diagnosed with Kleefstra syndrome, present a possible phenotype expansion to the syndrome and to raise physicians' awareness for this rare disease.</p></div><div><h3>Results</h3><p>seven patients with confirmed KS were evaluated, including 5 males and 2 females. Abnormal prenatal findings were observed in 4 patients. Most patients were born at term, with normal birth measurements. All patients had neurodevelopmental delay and 6 evolved with intellectual disability. Hearing loss was present in 57.1% of patients and 28.7% had congenital heart disease. In males, cryptorchidism was present in 75%. Despite the facial dysmorphisms, only 2 out of 7 patients had a pre-test clinical suspicion of KS. One specific patient presented bilateral agenesis of the semicircular canals, a very rare ear manifestation in Kleefstra syndrome, representing a possible phenotype expansion of the syndrome.</p></div><div><h3>Conclusion</h3><p>this report aims to promote awareness among physicians evaluating patients in a context of neurodevelopmental delay or congenital malformations, especially congenital heart defects. We also highlight a possible phenotype expansion of the syndrome, with a case of semicircular anomaly, not reported in this syndrome so far.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"71 ","pages":"Article 104966"},"PeriodicalIF":1.6,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000582/pdfft?md5=371bdbb5d8d212248eacb6a51f55b3fc&pid=1-s2.0-S1769721224000582-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987676","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 history of the international rare diseases research consortium (IRDiRC) and its conferences","authors":"","doi":"10.1016/j.ejmg.2024.104935","DOIUrl":"10.1016/j.ejmg.2024.104935","url":null,"abstract":"<div><p>Individual researchers and consortia have been studying rare diseases for several decades. However, the rare disease community can be very fragmented mainly due to the large heterogeneity of rare diseases. Indeed, for many diseases, there is a very limited amount of researchers and resources available. Concerted efforts to organize the rare disease community and funding were emerging in several countries but so far, international coordination was rather limited. The International Rare Diseases Research Consortium (IRDiRC) aims to correct this. A part of this requires bringing rare disease researchers together for an international conference.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"70 ","pages":"Article 104935"},"PeriodicalIF":1.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000272/pdfft?md5=91fd47c80bcc2493bcaf40d58874aae5&pid=1-s2.0-S1769721224000272-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597441","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":"Cardiovascular abnormalities in patients with SHANK3 pathogenic variants: Beyond neurodevelopmental disorders and epilepsy","authors":"Roger Esmel-Vilomara ,&nbsp;Lucy Dougherty-De Miguel ,&nbsp;Alícia Artigas-Baleri ,&nbsp;Eulàlia Turón-Viñas ,&nbsp;Ivon Cuscó ,&nbsp;Asunción Díaz-Gómez ,&nbsp;Luisa Panadés-De Oliveira ,&nbsp;Rodrigo Rocamora ,&nbsp;Susana Boronat","doi":"10.1016/j.ejmg.2024.104965","DOIUrl":"10.1016/j.ejmg.2024.104965","url":null,"abstract":"<div><p>Neurodevelopmental disorders have been linked to numerous genes, particularly pathogenic variants in genes encoding postsynaptic scaffolding proteins, like <em>SHANK3</em>. This study aims to provide insights into the cardiovascular profile of patients with pathogenic <em>SHANK3</em> variants, expanding beyond the well-established associations with neurodevelopmental disorders and epilepsy. We conducted a prospective study involving patients affected by neurodevelopmental disorders with pathogenic <em>SHANK3</em> variants. Comprehensive cardiovascular assessments were performed and molecular genetic testing included chromosomal microarray followed by clinical exome sequencing. We identified five patients with <em>de novo SHANK3</em> variants, all of whom exhibited cardiac involvement, including myocardial dysfunction, congenital heart disease (patent ductus arteriosus), and a case of postictal atrial fibrillation. Our findings emphasize an elevated risk of cardiovascular abnormalities in patients with <em>SHANK3</em> pathogenic variants compared to prior reports. Despite their young age, these patients displayed significant cardiac abnormalities. The study highlights the necessity of integrating cardiac evaluation and ongoing cardiovascular monitoring into multidisciplinary care, facilitating early detection of heart failure and assessment of the risk of sudden unexpected death in epilepsy (SUDEP). Further research is needed to elucidate the underlying mechanisms of cardiac manifestations in <em>SHANK3</em> mutation carriers.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"71 ","pages":"Article 104965"},"PeriodicalIF":1.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000570/pdfft?md5=a1784ad42810e49b34751a97798e94bb&pid=1-s2.0-S1769721224000570-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878534","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":"Demystifying gene(tic) therapies","authors":"Chun-Hung Chan ,&nbsp;David A. Pearce","doi":"10.1016/j.ejmg.2024.104963","DOIUrl":"10.1016/j.ejmg.2024.104963","url":null,"abstract":"<div><p>This article summarizes the discussion from a session entitled “Demystifying gene therapies” that was held at the joint RE(ACT) congress and IRDiRC conference, 14–15 March 2023 in Berlin, Germany. The focus of this session was to discuss the changing landscape of genetic therapies and whether current resources exist to provide adequate education to stakeholders, such as researchers, clinicians, patient advocates, legislators, as well as the patients and their families. The goal of this article is not to provide a comprehensive overview of the current landscape in genetic therapies, but rather to highlight resources that may be useful to help “demystify” the myriad of genetic therapeutic approaches.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"71 ","pages":"Article 104963"},"PeriodicalIF":1.6,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000557/pdfft?md5=03051b5d5212d03cc724e72f838a6890&pid=1-s2.0-S1769721224000557-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787617","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":"Phenotypic spectrum in Weiss-Kruszka syndrome caused by ZNF462 variants: Three new patients and literature review","authors":"Liselot van der Laan ,&nbsp;Lotte Kleinendorst ,&nbsp;Johanna M. van Hagen ,&nbsp;Quinten Waisfisz ,&nbsp;Mieke M. van Haelst","doi":"10.1016/j.ejmg.2024.104964","DOIUrl":"10.1016/j.ejmg.2024.104964","url":null,"abstract":"<div><p>Weiss-Kruszka Syndrome (WSKA) is caused by pathogenic variants in <em>ZNF462</em> representing a rare autosomal dominant congenital anomaly syndrome. It is characterized by global developmental delay, hypotonia, feeding difficulties, and craniofacial abnormalities, documented in fewer than 30 patients. ZNF462, located on chromosome 9p31.2, is a transcription factor and has an important role during embryonic development and chromatin remodelling. Here, we report three new patients with WSKA, Through whole exome sequencing (WES) analysis, we identified two novel variants in three patients, two of whom are siblings. These variants (c.3078dup, p.Val1027Cysfs5 and c.4792A &gt; T p.Lys1598*) in the <em>ZNF462</em> gene are likely resulting in haploinsufficiency. Our patients help to further delineate the phenotype, genotype and potential therapeutic management strategies for WSKA. Since we report a second WSKA patient with an autoimmune disease further clinical and functional studies are needed to elucidate the association between this chromatin remodelling disorder and the development of autoimmune problems. In the future, collaborative efforts are encouraged to develop an episignature for WSKA, given the gene's function and associated patient phenotypes. This new technology has the potential to provide valuable insights into the disorder.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"71 ","pages":"Article 104964"},"PeriodicalIF":1.6,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000569/pdfft?md5=e7c37a65efc47c0282bc4bdaa4ba0bc4&pid=1-s2.0-S1769721224000569-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787618","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":"Analysis of UGT1A1 genotype-phenotype correlation in Chinese patients with gilbert and crigler-Najjar II syndrome","authors":"Lina Wu ,&nbsp;Zhenkun Li ,&nbsp;Yi Song ,&nbsp;Yanmeng Li ,&nbsp;Wei Zhang ,&nbsp;Xuemei Zhong ,&nbsp;Xiaoming Wang ,&nbsp;Jian Huang ,&nbsp;Xiaojuan Ou","doi":"10.1016/j.ejmg.2024.104962","DOIUrl":"10.1016/j.ejmg.2024.104962","url":null,"abstract":"<div><p>The spectrum of UDP-glucuronosyltransferase (<em>UGT1A1</em>) variants, which are associated with Gilbert syndrome (GS) and Crigler-Najjar syndrome (CNS-II), has been reported in Chinese and western countries. However, the genotype-phenotype correlation of the individual <em>UGT1A1</em> variants in GS and CNS-II remains to be clarified. To explore the <em>UGT1A1</em> variant pattern and genotype-phenotype correlations, we enrolled 310 Chinese patients, including 232 patients with GS and 78 with CNS-II. Peripheral blood samples were collected for screening variants in the gene <em>UGT1A1</em> by a polymerase chain reaction and Sanger sequencing. The correlation between different <em>UGT1A1</em> variants and clinical phenotypes was analyzed. A total of 21 <em>UGT1A1</em> variants were identified, including nine novel variants, and constituted 42 <em>UGT1A1</em> genotypes in the GS and CNS-II patients. The most common <em>UGT1A1</em> variants were A (TA)₇TAA, p.G71R, p.Y486D, p.P364L, and p.P229Q, which were different from western countries. The p.Y486D variant had higher minor allele frequency in CNS-II than in GS whereas the A (TA)₇TAA variant had higher minor allele frequency in GS than in CNS-II. The serum total bilirubin and triglyceride had significant differences among 14 recurrent genotypes of <em>UGT1A1</em>, in which the serum total bilirubin in patients with compound p.Y486D (homozygous)/p.G71R variant was significantly higher compared with homozygous A (TA)₇TAA, homozygous p.G71R, compound heterozygous A (TA)₇TAA/p.G71R and A (TA)₇TAA/p.P364L, and combined heterozygous A (TA)₇TAA/p.G71R/p.P229Q, while the serum triglyceride in patients with combined A (TA)₇TAA (homozygous)/p.P229Q variant was significantly higher compared with compound heterozygous A (TA)₇TAA/p.G71R, single heterozygous A (TA)₇TAA, single heterozygous p.G71R, and homozygous A (TA)₇TAA. The spectrum of <em>UGT1A1</em> genotypes in Chinese patients was distinct from western countries. There were differential levels of serum total bilirubin and triglyceride in patients with recurrent genotypes of <em>UGT1A1</em>.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"71 ","pages":"Article 104962"},"PeriodicalIF":1.6,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000545/pdfft?md5=9e77faf37264755b09f453e41e49702e&pid=1-s2.0-S1769721224000545-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787616","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":"Attitudes towards disclosure of familial genetic risk in a Mediterranean island population – A survey of the Maltese population","authors":"Dillon Mintoff ,&nbsp;Bettina Booker ,&nbsp;Shannon Debono ,&nbsp;Matthias Farrugia ,&nbsp;Nikolai Paul Pace","doi":"10.1016/j.ejmg.2024.104961","DOIUrl":"10.1016/j.ejmg.2024.104961","url":null,"abstract":"<div><p>Germline genetic testing has implications that extend beyond the individual patient to relatives, particularly for high-penetrance variants implicated in hereditary cancer or neurodegenerative syndromes. Many countries encourage patient-led communication to inform at-risk relatives, although the efficacy and uptake of this approach varies. Alternative scenarios envisage direct contact mediated by clinicians. The familial disclosure of sensitive genetic information is also determined by complex socio-ethnic factors. To date, no study has explored whether relatives would want to be informed of familial genetic risk and their preferences on different methods of communication in Malta. We thus used a published instrument that utilizes hypothetical scenario methodology to survey the attitudes of the Maltese population (n = 334) to receiving genetic information from family members. Two vignettes on Huntington's disease and colorectal cancer were presented. We also explored preferences towards the communication of genetic risk, confidentiality, and disclosure policies. Our preliminary results show that most respondents want to be informed of their increased risk by a family member or a clinician and would opt to receive confirmatory genetic testing. Most respondents preferred being informed of genetic risk by a close relative, but in the case of non-disclosure would want to be informed by a clinician. Most respondents expressed preference in favour of the introduction of registries, legislative change and sharing of contact details to address cases of nondisclosure. Our findings contribute further to evidence that supports, in selected hypothetical scenarios, an envisioned change in disclosure of genetic data policy by the public that is different from current practice to date.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"71 ","pages":"Article 104961"},"PeriodicalIF":1.6,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000533/pdfft?md5=32967b439a1a6a2379787c84851abf01&pid=1-s2.0-S1769721224000533-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757898","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":"Increased frequency of infections and autoimmune disease in adults with PTEN Hamartoma Tumour Syndrome","authors":"Meggie M.C.M. Drissen ,&nbsp;Janet R. Vos ,&nbsp;Estel Collado Camps ,&nbsp;Janneke H.M. Schuurs-Hoeijmakers ,&nbsp;Jolanda H. Schieving ,&nbsp;Nicoline Hoogerbrugge","doi":"10.1016/j.ejmg.2024.104960","DOIUrl":"10.1016/j.ejmg.2024.104960","url":null,"abstract":"<div><p>There are indications for immune dysregulation in <em>PTEN</em> Hamartoma Tumour Syndrome (PHTS), however information on the clinical immune phenotype is lacking. We aimed to assess the frequency of infections and autoimmune disease in PHTS patients. A retrospective cohort study including 81 paediatric and 109 adult PHTS patients and 73 female adult controls and self-reported data from yearly surveillance visits. Differences between adult patients and controls were assessed with odds ratios (OR). Of paediatric patients, 1% reported fungal infections, 23% tonsillectomy/adenoidectomy, 36% bacterial infections requiring antibiotics, and 2% autoimmune disease. Of adult patients, up to 67% repeatedly reported fungal infections, and 73% was ever affected which was similar to controls. Compared to controls, adult patients more often reported (signs of) viral infections: tonsillectomy/adenoidectomy (78%; OR = 7.4 (95%CI: 3.7–15.8)), frequent infections during childhood (43%; OR = 2.5 (95%CI: 1.3–5.2)), and flu or cold infections more often than others (49%; OR = 3.9 (95%CI: 2.0–8.0)). Autoimmune disease was also more frequent (24%, OR = 2.7 (95%CI: 1.1–7.3)) in adult patients, and antibiotics use (38%, OR = 4.7 (95%CI: 1.3–23.0)) in female adult patients. PHTS patients experience a broad clinical phenotype of immune dysregulation. At adult age, this consists of more often viral and bacterial infections and autoimmune disease, and repetitive fungal infections.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"70 ","pages":"Article 104960"},"PeriodicalIF":1.6,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000521/pdfft?md5=ef7365bbdd76407b8376aea727ac5047&pid=1-s2.0-S1769721224000521-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723309","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":"Cancer in 22q11.2 deletion syndrome: A case report and literature review","authors":"Bingju Liu,&nbsp;Yunfeng Lu,&nbsp;Qi Wang,&nbsp;Yunpeng Dai,&nbsp;Liying Liu","doi":"10.1016/j.ejmg.2024.104959","DOIUrl":"10.1016/j.ejmg.2024.104959","url":null,"abstract":"<div><p>Clinically, the 22q11.2 deletion syndrome (22q11.2DS) is considered the most commonly detected microdeletion syndrome. Hepatoblastoma is the most prevalent malignant liver cancer in childhood. However, cases of hepatoblastoma in children with 22q11.2DS have only been reported in four patients. In this report, we present a-13-year-old male treated at our center due to growth retardation, and later diagnosed with hepatoblastoma. Whole genome sequencing (WGS) identified 22q11.2DS. Chromosomal microarray analysis (CMA) of peripheral blood sample showed a 2.9 Mb deletion of chromosome 22q11.2. While underlying mechanisms remain unclear, our literature review suggests that patients with 22q11.2DS may show an elevated risk of malignancy. After reviewing 21 previously reported cases, we identified 33 individuals with both cancer and 22q11.2 DS or DiGeorge syndrome. Of these cases, 7 out of 33 (21%) were hematologic tumors, while 26 out of 33 (78%) were solid tumors.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"70 ","pages":"Article 104959"},"PeriodicalIF":1.6,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S176972122400051X/pdfft?md5=f1fb3f662d0aaf05a591060f90c4b32c&pid=1-s2.0-S176972122400051X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537733","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":"Safety and efficacy of burosumab in improving phosphate metabolism, bone health, and quality of life in adolescents with X-linked hypophosphatemic rickets","authors":"Giampiero I. Baroncelli ,&nbsp;Anna Grandone ,&nbsp;Antonio Aversa ,&nbsp;Maria Rita Sessa ,&nbsp;Caterina Pelosini ,&nbsp;Angela Michelucci ,&nbsp;Benedetta Toschi ,&nbsp;Mario Manca ,&nbsp;Alessandro Isola ,&nbsp;Pasquale Comberiati","doi":"10.1016/j.ejmg.2024.104958","DOIUrl":"10.1016/j.ejmg.2024.104958","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background and objective&lt;/h3&gt;&lt;p&gt;X-linked hypophosphatemic rickets (XLH) is due to loss-of-function mutations in the phosphate-regulating endopeptidase homologue on the X chromosome (&lt;em&gt;PHEX&lt;/em&gt;) that lead to increased fibroblast growth factor 23 (FGF23) production. FGF23 excess causes renal phosphate wasting and insufficient 1,25-dihydroxyvitamin D (1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D) synthesis with reduced intestinal phosphate absorption, ultimately resulting in chronic hypophosphatemia.&lt;/p&gt;&lt;p&gt;Children with XLH show typical skeletal lesions of rickets, deformities of the lower limbs, stunted growth with disproportionate short stature, bone pain, and physical dysfunctions.&lt;/p&gt;&lt;p&gt;Burosumab, a fully human IgG1 monoclonal antibody that binds to FGF23 to inhibit its activity, is more effective to improve the biochemical and clinical signs of XLH than conventional treatment with phosphate supplements and vitamin D active metabolites. Data on adolescents with XLH during the transition period to young adulthood are few.&lt;/p&gt;&lt;p&gt;In this prospective case series, we aimed to assess safety and efficacy of burosumab in adolescents with XLH who discontinued long-term conventional therapy.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;Five Caucasian adolescents (4 males, 1 female; mean age 15.4 ± 1.5 years) with XLH were recruited and switched from conventional treatment to burosumab (0.8–1.2 mg/kg, s. c. QW2). Burosumab was continued for 12–48 months and, once discontinued, patients were followed-up for 6–12 months. In all patients, serum calcium, phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D levels, and renal tubular reabsorption of phosphate (TmP/GFR) values were assessed at entry and during burosumab. Intact FGF23 plasma levels were measured at entry. Patient-reported outcomes (PROs) were assessed at entry and every 3–6 months to evaluate the impact of low extremity pain, stiffness, and difficulties performing daily activities.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;At entry, all patients showed hypophosphatemia, increased intact FGF23 levels, reduced TmP/GFR, insufficient 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D levels, and in four out of five increased ALP levels. Two patients had radiological signs of rickets. During burosumab, all patients showed a significant increase in serum phosphate and 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D levels, and in TmP/GFR values (P &lt; 0.05 - P &lt; 0.0001). Serum ALP levels significantly declined (P &lt; 0.05) to normal values. No changes of serum calcium and PTH levels (P&lt;img&gt;NS) were found during burosumab. PROs significantly improved (P &lt; 0.02 - P &lt; 0.0001) in all patients. Four patients discontinued burosumab when they turned 18 or 19, whereas one continued the treatment since he was still younger than 18 during the study period. Four patients who suspended burosumab showed a rapid decline in serum phosphate and 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D levels and in TmP/GFR values; serum ALP levels increased, and PROs progressively worsened ","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"70 ","pages":"Article 104958"},"PeriodicalIF":1.6,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000508/pdfft?md5=1af36568f8c0c52967aa10a0676d7f49&pid=1-s2.0-S1769721224000508-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476240","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}