Delayed motor, mental and speech development and congenital brain malformations: the first description of Zhu–Tokita–Takenouchi–Kim syndrome in Russia
Zhu–Tokita–Takenouchi–Kim syndrome (ZTTK syndrome) is a rare autosomal dominant nuclear speckleopathy characterized by developmental delay, hypotonia, intellectual disability, facial dysmorphism in association with variable brain malformations, musculoskeletal abnormalities and ocular involvement. C...
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ABV-press
2024-05-01
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| Series: | Нервно-мышечные болезни |
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| author | O. B. Kondakova A. P. Gudkova S. V. Demyanov Yu. I. Davydova A. A. Lyalina D. I. Grebenkin E. A. Bakovich I. V. Kanivets D. S. Demyanov I. S. Zhanin A. A. Pushkov K. V. Savostyanov |
| author_facet | O. B. Kondakova A. P. Gudkova S. V. Demyanov Yu. I. Davydova A. A. Lyalina D. I. Grebenkin E. A. Bakovich I. V. Kanivets D. S. Demyanov I. S. Zhanin A. A. Pushkov K. V. Savostyanov |
| author_sort | O. B. Kondakova |
| collection | DOAJ |
| description | Zhu–Tokita–Takenouchi–Kim syndrome (ZTTK syndrome) is a rare autosomal dominant nuclear speckleopathy characterized by developmental delay, hypotonia, intellectual disability, facial dysmorphism in association with variable brain malformations, musculoskeletal abnormalities and ocular involvement. Currently, 87 cases of ZTTK syndrome have been described worldwide. The syndrome caused by mutations in the SON gene, located on the long arm of chromosome 21 (21q22.11). Nonsense and frameshift mutations have been described in the SON gene. Missense mutations, partial or whole gene deletions are less common.The aim of the work is to analyze the clinical picture and molecular genetic results of patients with confirmed ZTTK syndrome and compare them with data from foreign literature.We observed the one boy and two girls with ZTTK syndrome aged 13 months to 59 months, averaging about 38 months. DNA diagnostic was performed by next generation sequencing. All patients and all parents were confirmed by Sanger sequening. Three pathogenic variants were identified: c.5753_5756delTTAG (p.Val1918Glufs*87), c.1531del (p.Thr511Glnfs*9) and c.403delG (p.Glu135Asnfs*14). The first one was is most common, the other two are novel variants. Most patients had growth, motor and speech delay, seizures, hypotonia, congenital heart defects, urinary tract abnormalities and brain malformations. Comparative analysis of facial features in patients with ZTTK syndrome showed downslanting palpebral fissures, epicantal folds, broad or depressed nasal bridge, flared nares, smooth philtrum, thin upper lip and low set, rotated ears. The use of next generation sequencing as a first‑line test for research and diagnostic of ZTTK syndrome is advisable due to the pronounced clinical polymorphism. |
| format | Article |
| id | doaj-art-499cdba2decc4d8e80a4402bdf9d3597 |
| institution | DOAJ |
| issn | 2222-8721 2413-0443 |
| language | Russian |
| publishDate | 2024-05-01 |
| publisher | ABV-press |
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| series | Нервно-мышечные болезни |
| spelling | doaj-art-499cdba2decc4d8e80a4402bdf9d35972025-08-20T03:00:40ZrusABV-pressНервно-мышечные болезни2222-87212413-04432024-05-0114210.17650/2222-8721-2024-14-2-78-91386Delayed motor, mental and speech development and congenital brain malformations: the first description of Zhu–Tokita–Takenouchi–Kim syndrome in RussiaO. B. Kondakova0A. P. Gudkova1S. V. Demyanov2Yu. I. Davydova3A. A. Lyalina4D. I. Grebenkin5E. A. Bakovich6I. V. Kanivets7D. S. Demyanov8I. S. Zhanin9A. A. Pushkov10K. V. Savostyanov11National Medical Research Center for Children’s Health, Ministry of Health of RussiaI.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)National Medical Research Center for Children’s Health, Ministry of Health of RussiaNational Medical Research Center for Children’s Health, Ministry of Health of RussiaNational Medical Research Center for Children’s Health, Ministry of Health of RussiaNational Medical Research Center for Children’s Health, Ministry of Health of RussiaNational Medical Research Center for Children’s Health, Ministry of Health of RussiaNational Medical Research Center for Children’s Health, Ministry of Health of RussiaNational Medical Research Center for Children’s Health, Ministry of Health of RussiaNational Medical Research Center for Children’s Health, Ministry of Health of RussiaNational Medical Research Center for Children’s Health, Ministry of Health of RussiaNational Medical Research Center for Children’s Health, Ministry of Health of RussiaZhu–Tokita–Takenouchi–Kim syndrome (ZTTK syndrome) is a rare autosomal dominant nuclear speckleopathy characterized by developmental delay, hypotonia, intellectual disability, facial dysmorphism in association with variable brain malformations, musculoskeletal abnormalities and ocular involvement. Currently, 87 cases of ZTTK syndrome have been described worldwide. The syndrome caused by mutations in the SON gene, located on the long arm of chromosome 21 (21q22.11). Nonsense and frameshift mutations have been described in the SON gene. Missense mutations, partial or whole gene deletions are less common.The aim of the work is to analyze the clinical picture and molecular genetic results of patients with confirmed ZTTK syndrome and compare them with data from foreign literature.We observed the one boy and two girls with ZTTK syndrome aged 13 months to 59 months, averaging about 38 months. DNA diagnostic was performed by next generation sequencing. All patients and all parents were confirmed by Sanger sequening. Three pathogenic variants were identified: c.5753_5756delTTAG (p.Val1918Glufs*87), c.1531del (p.Thr511Glnfs*9) and c.403delG (p.Glu135Asnfs*14). The first one was is most common, the other two are novel variants. Most patients had growth, motor and speech delay, seizures, hypotonia, congenital heart defects, urinary tract abnormalities and brain malformations. Comparative analysis of facial features in patients with ZTTK syndrome showed downslanting palpebral fissures, epicantal folds, broad or depressed nasal bridge, flared nares, smooth philtrum, thin upper lip and low set, rotated ears. The use of next generation sequencing as a first‑line test for research and diagnostic of ZTTK syndrome is advisable due to the pronounced clinical polymorphism.https://nmb.abvpress.ru/jour/article/view/606zhu–tokita–takenouchi–kim syndromezttk syndromeson genepsychomotor development delaybrain malformationssplicing disordersnuclear specklesspecleopathies |
| spellingShingle | O. B. Kondakova A. P. Gudkova S. V. Demyanov Yu. I. Davydova A. A. Lyalina D. I. Grebenkin E. A. Bakovich I. V. Kanivets D. S. Demyanov I. S. Zhanin A. A. Pushkov K. V. Savostyanov Delayed motor, mental and speech development and congenital brain malformations: the first description of Zhu–Tokita–Takenouchi–Kim syndrome in Russia Нервно-мышечные болезни zhu–tokita–takenouchi–kim syndrome zttk syndrome son gene psychomotor development delay brain malformations splicing disorders nuclear speckles specleopathies |
| title | Delayed motor, mental and speech development and congenital brain malformations: the first description of Zhu–Tokita–Takenouchi–Kim syndrome in Russia |
| title_full | Delayed motor, mental and speech development and congenital brain malformations: the first description of Zhu–Tokita–Takenouchi–Kim syndrome in Russia |
| title_fullStr | Delayed motor, mental and speech development and congenital brain malformations: the first description of Zhu–Tokita–Takenouchi–Kim syndrome in Russia |
| title_full_unstemmed | Delayed motor, mental and speech development and congenital brain malformations: the first description of Zhu–Tokita–Takenouchi–Kim syndrome in Russia |
| title_short | Delayed motor, mental and speech development and congenital brain malformations: the first description of Zhu–Tokita–Takenouchi–Kim syndrome in Russia |
| title_sort | delayed motor mental and speech development and congenital brain malformations the first description of zhu tokita takenouchi kim syndrome in russia |
| topic | zhu–tokita–takenouchi–kim syndrome zttk syndrome son gene psychomotor development delay brain malformations splicing disorders nuclear speckles specleopathies |
| url | https://nmb.abvpress.ru/jour/article/view/606 |
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