European journal of medical genetics最新文献

{"title":"Associated anomalies in anophthalmia and microphthalmia","authors":"Claude Stoll,&nbsp;Beatrice Dott,&nbsp;Yves Alembik,&nbsp;Marie-Paule Roth","doi":"10.1016/j.ejmg.2023.104892","DOIUrl":"10.1016/j.ejmg.2023.104892","url":null,"abstract":"<div><p>Infants with anophthalmia and microphthalmia (an/microphthalmia) have often other associated congenital anomalies. The reported frequency and the types of these associated anomalies vary between different studies. The purpose of this investigation was to assess the frequency and the types of associated anomalies among cases with an/microphthalmia in a geographically well defined population of northeastern France of 387,067 consecutive pregnancies from 1979 to 2007. Of the 98 infants with an/microphthalmia born during this period (prevalence at birth of 2.53 per 10,000), 88.8 % had associated anomalies. Cases with associated anomalies were divided into recognizable conditions (25 (25.5%) cases with chromosomal and 17 (17.3%) cases with non chromosomal conditions), and non recognizable conditions (45–45.9%- cases with multiple congenital anomalies –MCA). Trisomy 13 and trisomy 18 were the most frequent chromosomal abnormalities. Amniotic bands sequence, oculo-auriculo-vertebral spectrum, CHARGE syndrome and VACTERL association were most often present in recognizable non chromosomal conditions. Anomalies in the musculoskeletal, cardiovascular and central nervous systems were the most common other anomalies in cases with MCA and non recognizable conditions. However, given the limitation of the limited numbers of cases there should be urging caution in interpreting these results. In conclusion the frequency of associated anomalies in infants with anophthalmia and microphthalmia emphasizes the need for a thorough investigation of these cases. Routine screening for other anomalies especially musculoskeletal, cardiac and central nervous systems anomalies may need to be considered in infants with anophthalmia and microphthalmia, and referral of these cases for genetic counselling seems warranty.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"67 ","pages":"Article 104892"},"PeriodicalIF":1.9,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721223001982/pdfft?md5=cbbb1e5ccfb2f35826c3ed31b9d6f4f4&pid=1-s2.0-S1769721223001982-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138679749","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":"LRP4 site-specific variants in the third β-propeller domain causes congenital myasthenic syndrome type 17","authors":"Tariq Al Jabry ,&nbsp;Nadia Al-Hashmi ,&nbsp;Basem Abdelhadi ,&nbsp;Almundher Al-Maawali","doi":"10.1016/j.ejmg.2023.104903","DOIUrl":"10.1016/j.ejmg.2023.104903","url":null,"abstract":"<div><p><em>LRP4</em> is expressed in many organs. It mediates SOST-dependent inhibition of bone formation and acts as an inhibitor of WNT signaling. It is also a postsynaptic end plate cell surface receptor at the neuromuscular junction and is central to its development, maintenance, and function. Pathogenic variants of <em>LRP4</em> that specifically affect the canonical WNT signaling pathway are known to be associated with Cenani-Lenz syndactyly syndrome or the overlapping condition sclerosteosis. However, site-specific pathogenic variants of <em>LRP4</em> have been associated with the congenital myasthenic syndrome (CMS) type 17 with no abnormal bone phenotype. Only two studies reported biallelic variants of <em>LRP4</em> associated with CMS17 that presented during childhood. All three reported variants (NM_002334.4: p.Glu1233Ala, p.Glu1233Lys, or p.Arg1277His) are located within the 3′-edge of the third β-propeller domain of LRP4. We report on a patient with a biallelic variant of the <em>LRP4</em> gene presenting with a severe and neonatal lethal phenotype; we also provide a literature review of the previously reported patients. A female neonate, born to healthy consanguineous parents, presented with severe hypotonia, congenital diaphragmatic hernia, pulmonary hypertension, and progressive hypoxemia. Two of her siblings presented with a similar condition in the past, and all three died shortly after birth. Clinical exome sequencing revealed homozygosity for the pathogenic variant NM_002334.4:c.3698A &gt; C (p.[Glu1233Ala]).</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"67 ","pages":"Article 104903"},"PeriodicalIF":1.9,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721223002094/pdfft?md5=ed9c8eac37ac901f64ef05065e309c9a&pid=1-s2.0-S1769721223002094-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138632372","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":"GRM7-related disorder: five additional patients from three independent families and review of the literature","authors":"Louis Januel ,&nbsp;Nicolas Chatron ,&nbsp;Clotilde Rivier-Ringenbach ,&nbsp;Sara Cabet ,&nbsp;Audrey Labalme ,&nbsp;Yavuz Sahin ,&nbsp;Hossein Darvish ,&nbsp;Michael Kruer ,&nbsp;Somayeh Bakhtiari ,&nbsp;Damien Sanlaville ,&nbsp;Jean Madeleine de Sainte Agathe ,&nbsp;Gaetan Lesca","doi":"10.1016/j.ejmg.2023.104893","DOIUrl":"10.1016/j.ejmg.2023.104893","url":null,"abstract":"<div><p><span>Developmental and epileptic encephalopathies (DEEs) refer to a group of severe epileptic syndromes characterized by seizures as well as a developmental delay which can be a consequence of the underlying etiology and/or the epileptic encephalopathy. The genes responsible for DEEs are numerous and their number is increasing since the availability of Next-Generation Sequencing. Pathogenic variants in </span><em>GRM7</em><span>, encoding the metabotropic glutamate receptor 7<span><span>, were recently shown as a cause of a severe DEE with autosomal recessive inheritance<span>. To date, only ten patients have been reported in the literature, generally with severe phenotypes including early-onset epilepsy, microcephaly, </span></span>brain anomalies, and spasticity. We report here 5 patients from 3 independent families with biallelic variants in the </span></span><em>GRM7</em> gene. We review the literature and provide further elements for the understanding of the genotype-phenotype correlation of this rare syndrome.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"67 ","pages":"Article 104893"},"PeriodicalIF":1.9,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138566973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined achondroplasia and short stature homeobox-containing (SHOX) gene deletion in a Danish infant","authors":"Kasper V. Seiersen ,&nbsp;Tine B. Henriksen ,&nbsp;Ted C.K. Andelius ,&nbsp;Lotte Andreasen ,&nbsp;Tue Diemer ,&nbsp;Gudrun Gudmundsdottir ,&nbsp;Ida Vogel ,&nbsp;Vibike Gjørup ,&nbsp;Pernille A. Gregersen","doi":"10.1016/j.ejmg.2023.104894","DOIUrl":"10.1016/j.ejmg.2023.104894","url":null,"abstract":"<div><p>Short stature or shortening of the limbs can be the result of a variety of genetic variants. Achondroplasia is the most common cause of disproportionate short stature and is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene <em>(FGFR3)</em>.</p><p>Short stature homeobox (SHOX) deficiency is caused by loss or defects of the <em>SHOX</em> gene or its enhancer region. It is associated with a spectrum of phenotypes ranging from normal stature to Léri-Weill dyschondrosteosis characterized by mesomelia and short stature or the more severe Langer mesomelic dysplasia in case of biallelic SHOX deficiency.</p><p>Little is known about the interactions and phenotypic consequences of achondroplasia in combination with SHOX deficiency, as the literature on this subject is scarce, and no genetically confirmed clinical reports exist. We present the clinical findings in an infant girl with concurrent achondroplasia and SHOX deficiency. We conclude that the clinical findings in infancy are phenotypically compatible with achondroplasia, with no features of the SHOX deficiency evident. This may change over time, as some features of SHOX deficiency only become evident later in life.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"67 ","pages":"Article 104894"},"PeriodicalIF":1.9,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721223002008/pdfft?md5=a4c39365537104cc37b290b8715b8271&pid=1-s2.0-S1769721223002008-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138567376","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":"Progressive myoclonic epilepsy as an expanding phenotype of NGLY1-associated congenital deglycosylation disorder: A case report and review of the literature","authors":"Yuri Sonoda ,&nbsp;Atsushi Fujita ,&nbsp;Michiko Torio ,&nbsp;Takahiko Mukaino ,&nbsp;Ayumi Sakata ,&nbsp;Masaru Matsukura ,&nbsp;Kousuke Yonemoto ,&nbsp;Ken Hatae ,&nbsp;Yuko Ichimiya ,&nbsp;Pin Fee Chong ,&nbsp;Masayuki Ochiai ,&nbsp;Yoshinao Wada ,&nbsp;Machiko Kadoya ,&nbsp;Nobuhiko Okamoto ,&nbsp;Yoshiko Murakami ,&nbsp;Tadashi Suzuki ,&nbsp;Noriko Isobe ,&nbsp;Hiroshi Shigeto ,&nbsp;Naomichi Matsumoto ,&nbsp;Yasunari Sakai ,&nbsp;Shouichi Ohga","doi":"10.1016/j.ejmg.2023.104895","DOIUrl":"10.1016/j.ejmg.2023.104895","url":null,"abstract":"<div><h3>Introduction</h3><p><em>NGLY1</em>-associated congenital disorder of deglycosylation (CDDG1: OMIM #<span>615273</span><svg><path></path></svg>) is a rare autosomal recessive disorder caused by a functional impairment of endoplasmic reticulum in degradation of glycoproteins. Neurocognitive dysfunctions have been documented in patients with CDDG1; however, deteriorating phenotypes of affected individuals remain elusive.</p></div><div><h3>Case presentation</h3><p>A Japanese boy with delayed psychomotor development showed ataxic movements from age 5 years and myoclonic seizures from age 12 years. Appetite loss, motor and cognitive decline became evident at age 12 years. Electrophysiological studies identified paroxysmal discharges on myoclonic seizure and a giant somatosensory evoked potential. Perampanel was effective for controlling myoclonic seizures. Exome sequencing revealed that the patient carried compound heterozygous variants in <em>NGLY1</em>, NM_018297.4: c.857G &gt; A and c.-17_12del, which were inherited from mother and father, respectively. A literature review confirmed that myoclonic seizures were observed in 28.5% of patients with epilepsy. No other patients had progressive myoclonic epilepsy or cognitive decline in association with loss-of-function variations in <em>NGLY1</em>.</p></div><div><h3>Conclusion</h3><p>Our data provides evidence that a group of patients with CDDG1 manifest slowly progressive myoclonic epilepsy and cognitive decline during the long-term clinical course.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"67 ","pages":"Article 104895"},"PeriodicalIF":1.9,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S176972122300201X/pdfft?md5=9d7033767721808e72668aad00d5b99e&pid=1-s2.0-S176972122300201X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138566972","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":"Clinical and molecular features of four families with CLDN10-related HELIX syndrome","authors":"Ahmad Qudair ,&nbsp;Maged Hussein ,&nbsp;Mohammed Alowain ,&nbsp;Zuhair Nasser Al-Hassnan ,&nbsp;Abdullah Alfaifi ,&nbsp;Abdullah Alfalah ,&nbsp;Mashael Al-Qahtani ,&nbsp;Fowzan S. Alkuraya","doi":"10.1016/j.ejmg.2023.104886","DOIUrl":"10.1016/j.ejmg.2023.104886","url":null,"abstract":"<div><p>Biallelic pathogenic variants in <em>CLDN10</em> cause the very rare and distinct <span>multiplex epithelium dysfunction manifested by hypohidrosis<span> and electrolyte imbalance (HELIX) syndrome</span></span><span><span>. HELIX patients often present with heat intolerance and reduced </span>tear secretion. Here, we report on eight new patients (four families) </span><span>who presented soon after birth with fine scales in the palms and soles and hypohidrosis that was associated with high body temperature.</span><span> Exome sequencing identified a novel homozygous pathogenic variant in </span><em>CLDN10</em><span> in one family (NM_006984:exon1:c.138G&gt;A:p.W46*) and a previously reported pathogenic founder variant in the other three (NM_006984:exon5:c.653del:P218Lfs*21). The detailed clinical reports of these patients and a review of previously reported patients further delineate the phenotype of this extremely rare disorder.</span></p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"66 12","pages":"Article 104886"},"PeriodicalIF":1.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138175957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","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":"L. Guimarães, Ruxanda Baião, Catarina Costa, M. Lemos, Margarida Rangel Henriques, Milena Paneque","doi":"10.1016/j.ejmg.2023.104908","DOIUrl":"https://doi.org/10.1016/j.ejmg.2023.104908","url":null,"abstract":"","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"73 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139023368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep intronic variant causes aberrant splicing of ATP7A in a family with a variable occipital horn syndrome phenotype","authors":"J. Harkness, Huw B. Thomas, J. Urquhart, Peter Jamieson, Raymond T. O'Keefe, Helen M. Kingston, Charulata Deshpande, William G. Newman","doi":"10.1016/j.ejmg.2023.104907","DOIUrl":"https://doi.org/10.1016/j.ejmg.2023.104907","url":null,"abstract":"","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"277 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139021324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining priorities in the transition from paediatric to adult healthcare for rare bone disease patients: a dialogic approach","authors":"D. Scognamiglio ,&nbsp;M. Boarini ,&nbsp;M.C. la Forgia ,&nbsp;E. Grippa ,&nbsp;S. Forni ,&nbsp;A. Sergi ,&nbsp;A. Romeo ,&nbsp;G. Massa ,&nbsp;L. Sangiorgi","doi":"10.1016/j.ejmg.2023.104891","DOIUrl":"10.1016/j.ejmg.2023.104891","url":null,"abstract":"<div><p>The Italian patient association for Multiple Osteochondromas, Ollier Disease, and Maffucci Syndrome, Associazione Conto Alla Rovescia-ACAR Aps, conducted a mixed-methods study at its 2023 annual conference. The study included the Open Dialogue Approach and a feedback survey to identify the main priorities in the transitioning process from paediatric to adult healthcare for patients with Multiple Osteochondromas, Ollier Disease, and Maffucci Syndrome.</p><p>The common needs identified by patients, families, caregivers, and healthcare professionals were coordination and continuity of care, patient empowerment and communication, social and practical support, and transition planning and support.</p><p>This experience fostered a sense of collaboration and cooperation among stakeholders, helping to build trust and create a shared vision for improving the quality of care for these patients. Furthermore, it could be considered a starting point for other patient associations interested in using different approaches to identify the needs of their members and actively involve all stakeholders.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"67 ","pages":"Article 104891"},"PeriodicalIF":1.9,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721223001970/pdfft?md5=e60faf7e0501489ecf8d70674fd7f82e&pid=1-s2.0-S1769721223001970-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138470057","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":"Secondary physical features in children with FASD","authors":"Miguel del Campo ,&nbsp;Julie A. Kable ,&nbsp;Claire D. Coles ,&nbsp;Michael Suttie ,&nbsp;Christina D. Chambers ,&nbsp;Gretchen Bandoli","doi":"10.1016/j.ejmg.2023.104890","DOIUrl":"10.1016/j.ejmg.2023.104890","url":null,"abstract":"<div><h3>Objective</h3><p><span><span>The diagnoses included within the umbrella term fetal alcohol spectrum disorders<span><span> (FASD), are based on the documentation of prenatal alcohol exposure (PAE), growth deficits and a pattern of dysmorphic physical features and neurobehavioral impairments. Although 3 key facial features (short </span>palpebral fissures, a smooth </span></span>philtrum and a thin vermilion of the upper lip) are the only </span>dysmorphic features<span> taken into account for the diagnosis of Fetal Alcohol Syndrome (FAS) or partial FAS (pFAS), several other features are commonly seen in individuals with these diagnoses. The goals of our study were to determine if some of these secondary physical features also occur more frequently in children with alcohol-related neurodevelopmental disorder (ARND) relative to controls, and if a cluster of these features combined in a dysmorphology score could be used to identify those negatively impacted by PAE but who do not have the cardinal physical features that led to a diagnosis of FAS or pFAS.</span></p></div><div><h3>Methods</h3><p>Among 2681 children recruited for the Collaboration on Fetal Alcohol Spectrum Disorders Prevalence (CoFASP) study, 1726 had an FASD or sufficient evidence of PAE having occurred or not in their pregnancy. Children were then categorized into groups using the modified Hoyme diagnostic criteria (FAS (n = 24), pFAS (n = 99) and ARND (n = 87), and No FASD (n = 1516), including those with No FASD and a history of PAE (No FASD/PAE, n = 498) and those with No FASD and no history of PAE (No FASD/No PAE, n = 1018). The frequencies of 26 secondary dysmorphic features were compared among these groups, both individually and combined in non-weighted and weighted dysmorphic scores. Correlations of the total dysmorphic scores with an index of overall cognitive ability were also compared by group status.</p></div><div><h3>Results</h3><p>Several of these features were significantly more frequent in children with FAS than in those with No FASD diagnosis with or without PAE but not in comparison to those with ARND. The number of features was also significantly higher in the FAS group as compared to all other groups for both weighted and unweighted dysmorphology scores but were not higher in the group with ARND when compared to the groups with No FASD either in the presence or absence of PAE. Although not diagnostic, higher total dysmorphology scores were predictive of lower general cognitive abilities in the group with ARND, suggesting severity of alcohol-related dysmorphology is predictive of severity of alcohol-related neurobehavioral impairment.</p></div><div><h3>Conclusion</h3><p>Secondary physical features were not more frequent in children with ARND compared to children without an FASD diagnosis but were a marker for lower cognitive function. The use of secondary physical features to support a diagnosis of ARND was not supported in this sample.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"67 ","pages":"Article 104890"},"PeriodicalIF":1.9,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138477084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}