A novel pathogenic variant of DNMT3A associated with craniosynostosis: a case report of Heyn–Sproul–Jackson syndrome
Pathogenic variants of DNMT3A have been implicated in Tatton-Brown-Rahman syndrome, an overgrowth disorder with macrocephaly and intellectual disability. However, there are recent reports of variants in the same gene giving rise to an opposing clinical phenotype presenting with microcephaly, growth...
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| Format: | Article |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2023.1165638/full |
| _version_ | 1797820509270835200 |
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| author | Ga Hye Kim Jaewon Kim Jaewoong Lee Dae-Hyun Jang |
| author_facet | Ga Hye Kim Jaewon Kim Jaewoong Lee Dae-Hyun Jang |
| author_sort | Ga Hye Kim |
| collection | DOAJ |
| description | Pathogenic variants of DNMT3A have been implicated in Tatton-Brown-Rahman syndrome, an overgrowth disorder with macrocephaly and intellectual disability. However, there are recent reports of variants in the same gene giving rise to an opposing clinical phenotype presenting with microcephaly, growth failure, and impaired development—named Heyn-Sproul-Jackson syndrome (HESJAS). Here, we present a case of HESJAS caused by a novel pathogenic variant of DNMT3A. A five-year-old girl presented with severe developmental delay. Perinatal and family history were non-contributory. Physical exam showed microcephaly and facial dysmorphic features, and neurodevelopmental assessments revealed profound global developmental delay. Brain magnetic resonance imaging findings were normal; however, brain 3D computed tomography revealed craniosynostosis. Next generation sequencing revealed a novel heterozygous variant in DNMT3A (NM_175629.2: c.1012_1014 + 3del). The patient's parents did not carry the variant. In this report, a novel feature associated with HESJAS (craniosynostosis) is described, along with a more detailed account of clinical manifestations than those in the original report. |
| first_indexed | 2024-03-13T09:39:26Z |
| format | Article |
| id | doaj.art-56299db52840472294498ff8783b2966 |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-03-13T09:39:26Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-56299db52840472294498ff8783b29662023-05-25T04:43:34ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602023-05-011110.3389/fped.2023.11656381165638A novel pathogenic variant of DNMT3A associated with craniosynostosis: a case report of Heyn–Sproul–Jackson syndromeGa Hye Kim0Jaewon Kim1Jaewoong Lee2Dae-Hyun Jang3Department of Rehabilitation Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Rehabilitation Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Laboratory Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Rehabilitation Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaPathogenic variants of DNMT3A have been implicated in Tatton-Brown-Rahman syndrome, an overgrowth disorder with macrocephaly and intellectual disability. However, there are recent reports of variants in the same gene giving rise to an opposing clinical phenotype presenting with microcephaly, growth failure, and impaired development—named Heyn-Sproul-Jackson syndrome (HESJAS). Here, we present a case of HESJAS caused by a novel pathogenic variant of DNMT3A. A five-year-old girl presented with severe developmental delay. Perinatal and family history were non-contributory. Physical exam showed microcephaly and facial dysmorphic features, and neurodevelopmental assessments revealed profound global developmental delay. Brain magnetic resonance imaging findings were normal; however, brain 3D computed tomography revealed craniosynostosis. Next generation sequencing revealed a novel heterozygous variant in DNMT3A (NM_175629.2: c.1012_1014 + 3del). The patient's parents did not carry the variant. In this report, a novel feature associated with HESJAS (craniosynostosis) is described, along with a more detailed account of clinical manifestations than those in the original report.https://www.frontiersin.org/articles/10.3389/fped.2023.1165638/fullHeyn-Sproul-Jackson syndromeDNMT3Acraniosynostosisnovel variantmicrocephaly |
| spellingShingle | Ga Hye Kim Jaewon Kim Jaewoong Lee Dae-Hyun Jang A novel pathogenic variant of DNMT3A associated with craniosynostosis: a case report of Heyn–Sproul–Jackson syndrome Frontiers in Pediatrics Heyn-Sproul-Jackson syndrome DNMT3A craniosynostosis novel variant microcephaly |
| title | A novel pathogenic variant of DNMT3A associated with craniosynostosis: a case report of Heyn–Sproul–Jackson syndrome |
| title_full | A novel pathogenic variant of DNMT3A associated with craniosynostosis: a case report of Heyn–Sproul–Jackson syndrome |
| title_fullStr | A novel pathogenic variant of DNMT3A associated with craniosynostosis: a case report of Heyn–Sproul–Jackson syndrome |
| title_full_unstemmed | A novel pathogenic variant of DNMT3A associated with craniosynostosis: a case report of Heyn–Sproul–Jackson syndrome |
| title_short | A novel pathogenic variant of DNMT3A associated with craniosynostosis: a case report of Heyn–Sproul–Jackson syndrome |
| title_sort | novel pathogenic variant of dnmt3a associated with craniosynostosis a case report of heyn sproul jackson syndrome |
| topic | Heyn-Sproul-Jackson syndrome DNMT3A craniosynostosis novel variant microcephaly |
| url | https://www.frontiersin.org/articles/10.3389/fped.2023.1165638/full |
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