Malan syndrome in a patient with 19p13.2p13.12 deletion encompassing NFIX and CACNA1A genes: Case report and review of the literature
Abstract Background Malan syndrome is a recently introduced overgrowth disorder described in a limited number of individuals. Haploinsufficiency and also point mutations of NFIX gene have been proposed as its leading causative mechanism, however, due to the limited number of cases and different dele...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-12-01
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| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.997 |
| _version_ | 1797847645315661824 |
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| author | Fernanda T. Bellucco Claudia B. deMello Vera A. Meloni Maria Isabel Melaragno |
| author_facet | Fernanda T. Bellucco Claudia B. deMello Vera A. Meloni Maria Isabel Melaragno |
| author_sort | Fernanda T. Bellucco |
| collection | DOAJ |
| description | Abstract Background Malan syndrome is a recently introduced overgrowth disorder described in a limited number of individuals. Haploinsufficiency and also point mutations of NFIX gene have been proposed as its leading causative mechanism, however, due to the limited number of cases and different deletion sizes, genotype/phenotype correlations are still limited. Methods Here, we report the first Brazilian case of Malan syndrome caused by a 990 kb deletion in 19p13.2p13.12, focusing on clinical and behavioral aspects of the syndrome. Results The patient presented with macrocephaly, facial dysmorphisms, hypotonia, developmental delay, moderate thoracolumbar scoliosis, and seizures. The intellectual and behavioral assessments showed severe cognitive, language, and adaptive functions impairments. The 19p deleted region of our patient encompasses NFIX, CACNA1A, which seems to be related to a higher frequency of seizures among individuals with microdeletions in 19p13.2, and 15 other coding genes, including CC2D1A and NACC1, both known to be involved in neurobiological process and pathways. Conclusion Deletions involving NFIX gene should be considered in patients with overgrowth during childhood, macrocephaly, developmental delay, and seizures, as well as severe intellectual disability. |
| first_indexed | 2024-04-09T18:14:46Z |
| format | Article |
| id | doaj.art-a0a29a93b3e24627b535d765e97af274 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-09T18:14:46Z |
| publishDate | 2019-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-a0a29a93b3e24627b535d765e97af2742023-04-13T05:27:13ZengWileyMolecular Genetics & Genomic Medicine2324-92692019-12-01712n/an/a10.1002/mgg3.997Malan syndrome in a patient with 19p13.2p13.12 deletion encompassing NFIX and CACNA1A genes: Case report and review of the literatureFernanda T. Bellucco0Claudia B. deMello1Vera A. Meloni2Maria Isabel Melaragno3Department of Morphology and Genetics Universidade Federal de São Paulo São Paulo BrazilDepartment of Psychobiology Universidade Federal de São Paulo São Paulo BrazilDepartment of Morphology and Genetics Universidade Federal de São Paulo São Paulo BrazilDepartment of Morphology and Genetics Universidade Federal de São Paulo São Paulo BrazilAbstract Background Malan syndrome is a recently introduced overgrowth disorder described in a limited number of individuals. Haploinsufficiency and also point mutations of NFIX gene have been proposed as its leading causative mechanism, however, due to the limited number of cases and different deletion sizes, genotype/phenotype correlations are still limited. Methods Here, we report the first Brazilian case of Malan syndrome caused by a 990 kb deletion in 19p13.2p13.12, focusing on clinical and behavioral aspects of the syndrome. Results The patient presented with macrocephaly, facial dysmorphisms, hypotonia, developmental delay, moderate thoracolumbar scoliosis, and seizures. The intellectual and behavioral assessments showed severe cognitive, language, and adaptive functions impairments. The 19p deleted region of our patient encompasses NFIX, CACNA1A, which seems to be related to a higher frequency of seizures among individuals with microdeletions in 19p13.2, and 15 other coding genes, including CC2D1A and NACC1, both known to be involved in neurobiological process and pathways. Conclusion Deletions involving NFIX gene should be considered in patients with overgrowth during childhood, macrocephaly, developmental delay, and seizures, as well as severe intellectual disability.https://doi.org/10.1002/mgg3.99719p13.2 microdeletionCACNA1AMalan syndromeNFIXovergrowth disorder |
| spellingShingle | Fernanda T. Bellucco Claudia B. deMello Vera A. Meloni Maria Isabel Melaragno Malan syndrome in a patient with 19p13.2p13.12 deletion encompassing NFIX and CACNA1A genes: Case report and review of the literature Molecular Genetics & Genomic Medicine 19p13.2 microdeletion CACNA1A Malan syndrome NFIX overgrowth disorder |
| title | Malan syndrome in a patient with 19p13.2p13.12 deletion encompassing NFIX and CACNA1A genes: Case report and review of the literature |
| title_full | Malan syndrome in a patient with 19p13.2p13.12 deletion encompassing NFIX and CACNA1A genes: Case report and review of the literature |
| title_fullStr | Malan syndrome in a patient with 19p13.2p13.12 deletion encompassing NFIX and CACNA1A genes: Case report and review of the literature |
| title_full_unstemmed | Malan syndrome in a patient with 19p13.2p13.12 deletion encompassing NFIX and CACNA1A genes: Case report and review of the literature |
| title_short | Malan syndrome in a patient with 19p13.2p13.12 deletion encompassing NFIX and CACNA1A genes: Case report and review of the literature |
| title_sort | malan syndrome in a patient with 19p13 2p13 12 deletion encompassing nfix and cacna1a genes case report and review of the literature |
| topic | 19p13.2 microdeletion CACNA1A Malan syndrome NFIX overgrowth disorder |
| url | https://doi.org/10.1002/mgg3.997 |
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