Vici syndrome in Israel: Clinical and molecular insights
Introduction: Vici Syndrome is a rare, severe, neurodevelopmental/neurodegenerative disorder with multi-systemic manifestations presenting in infancy. It is mainly characterized by global developmental delay, seizures, agenesis of the corpus callosum, hair and skin hypopigmentation, bilateral catara...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.991721/full |
| _version_ | 1818021339668152320 |
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| author | Odelia Chorin Odelia Chorin Odelia Chorin Yoel Hirsch Rachel Rock Rachel Rock Rachel Rock Liat Salzer Sheelo Liat Salzer Sheelo Yael Goldberg Yael Goldberg Hanna Mandel Hanna Mandel Tova Hershkovitz Tova Hershkovitz Nicole Fleischer Lior Greenbaum Lior Greenbaum Lior Greenbaum Uriel Katz Uriel Katz Ortal Barel Ortal Barel Nasrin Hamed Nasrin Hamed Bruria Ben-Zeev Bruria Ben-Zeev Shoshana Greenberger Shoshana Greenberger Shoshana Greenberger Nadra Nasser Samra Nadra Nasser Samra Michal Stern Zimmer Michal Stern Zimmer Michal Stern Zimmer Annick Raas-Rothschild Annick Raas-Rothschild Ben Pode-Shakked Ben Pode-Shakked Ben Pode-Shakked |
| author_facet | Odelia Chorin Odelia Chorin Odelia Chorin Yoel Hirsch Rachel Rock Rachel Rock Rachel Rock Liat Salzer Sheelo Liat Salzer Sheelo Yael Goldberg Yael Goldberg Hanna Mandel Hanna Mandel Tova Hershkovitz Tova Hershkovitz Nicole Fleischer Lior Greenbaum Lior Greenbaum Lior Greenbaum Uriel Katz Uriel Katz Ortal Barel Ortal Barel Nasrin Hamed Nasrin Hamed Bruria Ben-Zeev Bruria Ben-Zeev Shoshana Greenberger Shoshana Greenberger Shoshana Greenberger Nadra Nasser Samra Nadra Nasser Samra Michal Stern Zimmer Michal Stern Zimmer Michal Stern Zimmer Annick Raas-Rothschild Annick Raas-Rothschild Ben Pode-Shakked Ben Pode-Shakked Ben Pode-Shakked |
| author_sort | Odelia Chorin |
| collection | DOAJ |
| description | Introduction: Vici Syndrome is a rare, severe, neurodevelopmental/neurodegenerative disorder with multi-systemic manifestations presenting in infancy. It is mainly characterized by global developmental delay, seizures, agenesis of the corpus callosum, hair and skin hypopigmentation, bilateral cataract, and varying degrees of immunodeficiency, among other features. Vici Syndrome is caused by biallelic pathogenic variants in EPG5, resulting in impaired autophagy. Thus far, the condition has been reported in less than a hundred individuals.Objective and Methods: We aimed to characterize the clinical and molecular findings in individuals harboring biallelic EPG5 variants, recruited from four medical centers in Israel. Furthermore, we aimed to utilize a machine learning-based tool to assess facial features of Vici syndrome.Results: Eleven cases of Vici Syndrome from five unrelated families, one of which was diagnosed prenatally with subsequent termination of pregnancy, were recruited. A total of five disease causing variants were detected in EPG5: two novel: c.2554-5A>G and c.1461delC; and 3 previously reported: c.3447G>A, c.5993C>G, and c.1007A>G, the latter previously identified in several patients of Ashkenazi-Jewish (AJ) descent. Amongst 140,491 individuals screened by the Dor Yeshorim Program, we show that the c.1007A>G variant has an overall carrier frequency of 0.45% (1 in 224) among AJ individuals. Finally, based on two-dimensional facial photographs of individuals with Vici syndrome (n = 19), a composite facial mask was created using the DeepGestalt algorithm, illustrating facial features typical of this disorder.Conclusion: We report on ten children and one fetus from five unrelated families, affected with Vici syndrome, and describe prenatal and postnatal characteristics. Our findings contribute to the current knowledge regarding the molecular basis and phenotypic features of this rare syndrome. Additionally, the deep learning-based facial gestalt adds to the clinician’s diagnostic toolbox and may aid in facilitating identification of affected individuals. |
| first_indexed | 2024-04-14T08:16:48Z |
| format | Article |
| id | doaj.art-8e8a48b5d2af47e29c4d8e95ea739427 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-14T08:16:48Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-8e8a48b5d2af47e29c4d8e95ea7394272022-12-22T02:04:22ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-09-011310.3389/fgene.2022.991721991721Vici syndrome in Israel: Clinical and molecular insightsOdelia Chorin0Odelia Chorin1Odelia Chorin2Yoel Hirsch3Rachel Rock4Rachel Rock5Rachel Rock6Liat Salzer Sheelo7Liat Salzer Sheelo8Yael Goldberg9Yael Goldberg10Hanna Mandel11Hanna Mandel12Tova Hershkovitz13Tova Hershkovitz14Nicole Fleischer15Lior Greenbaum16Lior Greenbaum17Lior Greenbaum18Uriel Katz19Uriel Katz20Ortal Barel21Ortal Barel22Nasrin Hamed23Nasrin Hamed24Bruria Ben-Zeev25Bruria Ben-Zeev26Shoshana Greenberger27Shoshana Greenberger28Shoshana Greenberger29Nadra Nasser Samra30Nadra Nasser Samra31Michal Stern Zimmer32Michal Stern Zimmer33Michal Stern Zimmer34Annick Raas-Rothschild35Annick Raas-Rothschild36Ben Pode-Shakked37Ben Pode-Shakked38Ben Pode-Shakked39The Institute for Rare Diseases, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Ramat Gan, IsraelThe Danek Gertner Institute of Human Genetics, Sheba Medical Center, Ramat Gan, IsraelSackler Faculty of Medicine, Tel-Aviv University, Tel Aviv-Yafo, IsraelDor Yeshorim, Committee for Prevention of Jewish Genetic Diseases, New York, NY, United StatesThe Institute for Rare Diseases, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Ramat Gan, IsraelThe Danek Gertner Institute of Human Genetics, Sheba Medical Center, Ramat Gan, IsraelSackler Faculty of Medicine, Tel-Aviv University, Tel Aviv-Yafo, IsraelSackler Faculty of Medicine, Tel-Aviv University, Tel Aviv-Yafo, IsraelRaphael Recanati Genetic Institute, Rabin Medical Center—Beilinson Hospital, Petah Tikva, IsraelSackler Faculty of Medicine, Tel-Aviv University, Tel Aviv-Yafo, IsraelRaphael Recanati Genetic Institute, Rabin Medical Center—Beilinson Hospital, Petah Tikva, IsraelUnit of Inherited Metabolic Disorders, Ziv Medical Center, Safed, IsraelInstitute of Human Genetics, Ziv Medical Center, Safed, IsraelThe Genetics Institute, Rambam Health Care Campus, Haifa, IsraelRuth and Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel0FDNA Inc, Boston, MA, United StatesThe Danek Gertner Institute of Human Genetics, Sheba Medical Center, Ramat Gan, IsraelSackler Faculty of Medicine, Tel-Aviv University, Tel Aviv-Yafo, Israel1The Joseph Sagol Neusroscience Center, Sheba Medical Center, Ramat Gan, IsraelSackler Faculty of Medicine, Tel-Aviv University, Tel Aviv-Yafo, Israel2Pediatric Heart Institute, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Ramat Gan, Israel3The Genomic Unit, Sheba Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel4The Wohl Institute for Translational Medicine and Cancer Research Center, Sheba Medical Center, Ramat Gan, IsraelSackler Faculty of Medicine, Tel-Aviv University, Tel Aviv-Yafo, Israel5Pediatric Neurology Unit, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Ramat Gan, IsraelSackler Faculty of Medicine, Tel-Aviv University, Tel Aviv-Yafo, Israel5Pediatric Neurology Unit, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Ramat Gan, IsraelSackler Faculty of Medicine, Tel-Aviv University, Tel Aviv-Yafo, Israel6The Talpiot Medical Leadership Program, Sheba Medical Center, Ramat Gan, Israel7Department of Dermatology, Sheba Medical Center, Ramat Gan, IsraelInstitute of Human Genetics, Ziv Medical Center, Safed, Israel8Azrieli Faculty of Medicine, Bar-Ilan University, Safed, IsraelSackler Faculty of Medicine, Tel-Aviv University, Tel Aviv-Yafo, Israel5Pediatric Neurology Unit, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Ramat Gan, Israel9Pediatric Department B, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Ramat Gan, IsraelThe Institute for Rare Diseases, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Ramat Gan, IsraelSackler Faculty of Medicine, Tel-Aviv University, Tel Aviv-Yafo, IsraelThe Institute for Rare Diseases, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Ramat Gan, IsraelSackler Faculty of Medicine, Tel-Aviv University, Tel Aviv-Yafo, Israel6The Talpiot Medical Leadership Program, Sheba Medical Center, Ramat Gan, IsraelIntroduction: Vici Syndrome is a rare, severe, neurodevelopmental/neurodegenerative disorder with multi-systemic manifestations presenting in infancy. It is mainly characterized by global developmental delay, seizures, agenesis of the corpus callosum, hair and skin hypopigmentation, bilateral cataract, and varying degrees of immunodeficiency, among other features. Vici Syndrome is caused by biallelic pathogenic variants in EPG5, resulting in impaired autophagy. Thus far, the condition has been reported in less than a hundred individuals.Objective and Methods: We aimed to characterize the clinical and molecular findings in individuals harboring biallelic EPG5 variants, recruited from four medical centers in Israel. Furthermore, we aimed to utilize a machine learning-based tool to assess facial features of Vici syndrome.Results: Eleven cases of Vici Syndrome from five unrelated families, one of which was diagnosed prenatally with subsequent termination of pregnancy, were recruited. A total of five disease causing variants were detected in EPG5: two novel: c.2554-5A>G and c.1461delC; and 3 previously reported: c.3447G>A, c.5993C>G, and c.1007A>G, the latter previously identified in several patients of Ashkenazi-Jewish (AJ) descent. Amongst 140,491 individuals screened by the Dor Yeshorim Program, we show that the c.1007A>G variant has an overall carrier frequency of 0.45% (1 in 224) among AJ individuals. Finally, based on two-dimensional facial photographs of individuals with Vici syndrome (n = 19), a composite facial mask was created using the DeepGestalt algorithm, illustrating facial features typical of this disorder.Conclusion: We report on ten children and one fetus from five unrelated families, affected with Vici syndrome, and describe prenatal and postnatal characteristics. Our findings contribute to the current knowledge regarding the molecular basis and phenotypic features of this rare syndrome. Additionally, the deep learning-based facial gestalt adds to the clinician’s diagnostic toolbox and may aid in facilitating identification of affected individuals.https://www.frontiersin.org/articles/10.3389/fgene.2022.991721/fullEPG5Vici syndromecongenital cataractagenesis of corpus callosumglobal developmental delaycardiomyopathy |
| spellingShingle | Odelia Chorin Odelia Chorin Odelia Chorin Yoel Hirsch Rachel Rock Rachel Rock Rachel Rock Liat Salzer Sheelo Liat Salzer Sheelo Yael Goldberg Yael Goldberg Hanna Mandel Hanna Mandel Tova Hershkovitz Tova Hershkovitz Nicole Fleischer Lior Greenbaum Lior Greenbaum Lior Greenbaum Uriel Katz Uriel Katz Ortal Barel Ortal Barel Nasrin Hamed Nasrin Hamed Bruria Ben-Zeev Bruria Ben-Zeev Shoshana Greenberger Shoshana Greenberger Shoshana Greenberger Nadra Nasser Samra Nadra Nasser Samra Michal Stern Zimmer Michal Stern Zimmer Michal Stern Zimmer Annick Raas-Rothschild Annick Raas-Rothschild Ben Pode-Shakked Ben Pode-Shakked Ben Pode-Shakked Vici syndrome in Israel: Clinical and molecular insights Frontiers in Genetics EPG5 Vici syndrome congenital cataract agenesis of corpus callosum global developmental delay cardiomyopathy |
| title | Vici syndrome in Israel: Clinical and molecular insights |
| title_full | Vici syndrome in Israel: Clinical and molecular insights |
| title_fullStr | Vici syndrome in Israel: Clinical and molecular insights |
| title_full_unstemmed | Vici syndrome in Israel: Clinical and molecular insights |
| title_short | Vici syndrome in Israel: Clinical and molecular insights |
| title_sort | vici syndrome in israel clinical and molecular insights |
| topic | EPG5 Vici syndrome congenital cataract agenesis of corpus callosum global developmental delay cardiomyopathy |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.991721/full |
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