Analyzing clinical and genetic characteristics of a cohort with multiple congenital anomalies-hypotonia-seizures syndrome (MCAHS)
Abstract Objective To summarize and extend the phenotypic characterization of Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome, and to discuss genotype-phenotype correlations. Methods Collecting clinical information of 17 patients with pathogenic variants in PIGN, PIGA, and PIGT. Genetic st...
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| Format: | Article |
| Language: | English |
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BMC
2020-03-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | http://link.springer.com/article/10.1186/s13023-020-01365-0 |
| _version_ | 1828763274711138304 |
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| author | Xianru Jiao Jiao Xue Pan Gong Xinhua Bao Ye Wu Yuehua Zhang Yuwu Jiang Zhixian Yang |
| author_facet | Xianru Jiao Jiao Xue Pan Gong Xinhua Bao Ye Wu Yuehua Zhang Yuwu Jiang Zhixian Yang |
| author_sort | Xianru Jiao |
| collection | DOAJ |
| description | Abstract Objective To summarize and extend the phenotypic characterization of Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome, and to discuss genotype-phenotype correlations. Methods Collecting clinical information of 17 patients with pathogenic variants in PIGN, PIGA, and PIGT. Genetic studies were performed on all patients. Results There were 7 patients with 15 PIGN mutations (one patient carrying 3 mutations), 8 patients with 8 PIGA mutations, and 2 patients with 5 PIGT mutations (one patient carrying 3 mutations). All patients had epilepsy and developmental delay, with 71% of them showed hypotonia. And among these patients’ various seizure types, the focal seizure was the most common one. Eighty-two percent patients showed a significant relationship between seizures and fever. Serum ALP was elevated in one patient with PIGN mutations and in two patients with PIGA mutations. Brain MRI showed enlarged subarachnoid space in 56% of patients. Some other different characteristics had also been found in our patients: First, atypical absence seizures presented in three patients with PIGN mutations; Second, diffuse slow waves mixed with focal or multifocal discharges of interictal EEG in 88% cases with PIGA-deficient; Third, phenotypes of seven out of eight patients with PIGA mutations were difficult to be classified as severe or less severe group; Last, mild neurological symptoms and developmental status rather than severe conditions occurred in one patient with PIGT mutations. Conclusion With epilepsy, developmental delay, and/or hypotonia as common features, the knowledge of MCAHS in terms of phenotype and genotype has been expanded. In cases with PIGN-deficient, we expanded the types of atypical absence seizures, and described one patient with elevated serum ALP. Focal seizures with diffuse slow waves mixed with focal or multifocal discharges on EEG rather than infantile spasms with hypsarrhythmia, which as previously reported were often seen in our patients with PIGA mutations. The classifications of phenotypes caused by PIGA mutations should be more continuous than discrete. The mild phenotype of one patient with PIGT mutations expanded the clinical presentation of MCAHS3. |
| first_indexed | 2024-12-11T01:58:01Z |
| format | Article |
| id | doaj.art-f21b52c5319549e0b8d82cc218e1fdea |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-11T01:58:01Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-f21b52c5319549e0b8d82cc218e1fdea2022-12-22T01:24:35ZengBMCOrphanet Journal of Rare Diseases1750-11722020-03-0115111210.1186/s13023-020-01365-0Analyzing clinical and genetic characteristics of a cohort with multiple congenital anomalies-hypotonia-seizures syndrome (MCAHS)Xianru Jiao0Jiao Xue1Pan Gong2Xinhua Bao3Ye Wu4Yuehua Zhang5Yuwu Jiang6Zhixian Yang7Department of Pediatrics, Peking University First HospitalDepartment of Pediatrics, Peking University First HospitalDepartment of Pediatrics, Peking University First HospitalDepartment of Pediatrics, Peking University First HospitalDepartment of Pediatrics, Peking University First HospitalDepartment of Pediatrics, Peking University First HospitalDepartment of Pediatrics, Peking University First HospitalDepartment of Pediatrics, Peking University First HospitalAbstract Objective To summarize and extend the phenotypic characterization of Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome, and to discuss genotype-phenotype correlations. Methods Collecting clinical information of 17 patients with pathogenic variants in PIGN, PIGA, and PIGT. Genetic studies were performed on all patients. Results There were 7 patients with 15 PIGN mutations (one patient carrying 3 mutations), 8 patients with 8 PIGA mutations, and 2 patients with 5 PIGT mutations (one patient carrying 3 mutations). All patients had epilepsy and developmental delay, with 71% of them showed hypotonia. And among these patients’ various seizure types, the focal seizure was the most common one. Eighty-two percent patients showed a significant relationship between seizures and fever. Serum ALP was elevated in one patient with PIGN mutations and in two patients with PIGA mutations. Brain MRI showed enlarged subarachnoid space in 56% of patients. Some other different characteristics had also been found in our patients: First, atypical absence seizures presented in three patients with PIGN mutations; Second, diffuse slow waves mixed with focal or multifocal discharges of interictal EEG in 88% cases with PIGA-deficient; Third, phenotypes of seven out of eight patients with PIGA mutations were difficult to be classified as severe or less severe group; Last, mild neurological symptoms and developmental status rather than severe conditions occurred in one patient with PIGT mutations. Conclusion With epilepsy, developmental delay, and/or hypotonia as common features, the knowledge of MCAHS in terms of phenotype and genotype has been expanded. In cases with PIGN-deficient, we expanded the types of atypical absence seizures, and described one patient with elevated serum ALP. Focal seizures with diffuse slow waves mixed with focal or multifocal discharges on EEG rather than infantile spasms with hypsarrhythmia, which as previously reported were often seen in our patients with PIGA mutations. The classifications of phenotypes caused by PIGA mutations should be more continuous than discrete. The mild phenotype of one patient with PIGT mutations expanded the clinical presentation of MCAHS3.http://link.springer.com/article/10.1186/s13023-020-01365-0Glycosylphosphatidylinositol anchorEpilepsyHypotoniaDevelopmental delayDysmorphism |
| spellingShingle | Xianru Jiao Jiao Xue Pan Gong Xinhua Bao Ye Wu Yuehua Zhang Yuwu Jiang Zhixian Yang Analyzing clinical and genetic characteristics of a cohort with multiple congenital anomalies-hypotonia-seizures syndrome (MCAHS) Orphanet Journal of Rare Diseases Glycosylphosphatidylinositol anchor Epilepsy Hypotonia Developmental delay Dysmorphism |
| title | Analyzing clinical and genetic characteristics of a cohort with multiple congenital anomalies-hypotonia-seizures syndrome (MCAHS) |
| title_full | Analyzing clinical and genetic characteristics of a cohort with multiple congenital anomalies-hypotonia-seizures syndrome (MCAHS) |
| title_fullStr | Analyzing clinical and genetic characteristics of a cohort with multiple congenital anomalies-hypotonia-seizures syndrome (MCAHS) |
| title_full_unstemmed | Analyzing clinical and genetic characteristics of a cohort with multiple congenital anomalies-hypotonia-seizures syndrome (MCAHS) |
| title_short | Analyzing clinical and genetic characteristics of a cohort with multiple congenital anomalies-hypotonia-seizures syndrome (MCAHS) |
| title_sort | analyzing clinical and genetic characteristics of a cohort with multiple congenital anomalies hypotonia seizures syndrome mcahs |
| topic | Glycosylphosphatidylinositol anchor Epilepsy Hypotonia Developmental delay Dysmorphism |
| url | http://link.springer.com/article/10.1186/s13023-020-01365-0 |
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