Galloway-Mowat syndrome in Taiwan: OSGEP mutation and unique clinical phenotype
Abstract Background Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive disease characterized by the combination of glomerulopathy with early-onset nephrotic syndrome and microcephaly with central nervous system anomalies. Given its clinical heterogeneity, GAMOS is believed to be a genetic...
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| Format: | Article |
| Language: | English |
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BMC
2018-12-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13023-018-0961-9 |
| _version_ | 1818247122926960640 |
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| author | Pei-Yi Lin Min-Hua Tseng Martin Zenker Jia Rao Friedhelm Hildebrandt Shih-Hua Lin Chun-Chen Lin Jui-Hsing Chang Chyong-Hsin Hsu Ming-Dar Lee Shuan-Pei Lin Jeng-Daw Tsai |
| author_facet | Pei-Yi Lin Min-Hua Tseng Martin Zenker Jia Rao Friedhelm Hildebrandt Shih-Hua Lin Chun-Chen Lin Jui-Hsing Chang Chyong-Hsin Hsu Ming-Dar Lee Shuan-Pei Lin Jeng-Daw Tsai |
| author_sort | Pei-Yi Lin |
| collection | DOAJ |
| description | Abstract Background Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive disease characterized by the combination of glomerulopathy with early-onset nephrotic syndrome and microcephaly with central nervous system anomalies. Given its clinical heterogeneity, GAMOS is believed to be a genetically heterogenous group of disorders. Recently, it has been reported that mutations in KEOPS-encoding genes, including the OSGEP gene, were responsible for GAMOS. Results Overall, 6 patients from 5 different Taiwanese families were included in our study; the patients had an identical OSGEP gene mutation (c.740G > A transition) and all exhibited a uniform clinical phenotype with early-onset nephrotic syndrome, craniofacial and skeletal dysmorphism, primary microcephaly with pachygyria, and death before 2 years of age. We reviewed their clinical manifestations, the prenatal and postnatal presentations and ultrasound findings, results of imaging studies, associated anomalies, and outcome on follow-up. All individuals were found to have an “aged face” comprising peculiar facial dysmorphisms. Arachnodactyly or camptodactyly were noted in all patients. Neurological findings consisted of microcephaly, hypotonia, developmental delay, and seizures. Brain imaging studies all showed pachygyria and hypomyelination. All patients developed early-onset nephrotic syndrome. The proteinuria was steroid-resistant and eventually resulted in renal function impairment. Prenatal ultrasound findings included microcephaly, intrauterine growth restriction, and oligohydramnios. Fetal MRI in 2 patients confirmed the gyral and myelin abnormalities. Conclusions Our study suggests that a careful review of the facial features can provide useful clues for an early and accurate diagnosis. Prenatal ultrasound findings, fetal MRI, genetic counseling, and mutation analysis may be useful for an early prenatal diagnosis. |
| first_indexed | 2024-12-12T14:59:41Z |
| format | Article |
| id | doaj.art-85f645afb83c4d01a27a82ae55b49213 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-12T14:59:41Z |
| publishDate | 2018-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-85f645afb83c4d01a27a82ae55b492132022-12-22T00:20:49ZengBMCOrphanet Journal of Rare Diseases1750-11722018-12-011311910.1186/s13023-018-0961-9Galloway-Mowat syndrome in Taiwan: OSGEP mutation and unique clinical phenotypePei-Yi Lin0Min-Hua Tseng1Martin Zenker2Jia Rao3Friedhelm Hildebrandt4Shih-Hua Lin5Chun-Chen Lin6Jui-Hsing Chang7Chyong-Hsin Hsu8Ming-Dar Lee9Shuan-Pei Lin10Jeng-Daw Tsai11Department of Pediatrics, MacKay Children’s HospitalDivision of Pediatric Nephrology, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung UniversityInstitute of Human Genetics, University Hospital MagdeburgDepartment of Medicine, Boston Children’s Hospital, Harvard Medical SchoolDepartment of Medicine, Boston Children’s Hospital, Harvard Medical SchoolDivision of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical CenterDepartment of Pediatrics, MacKay Children’s HospitalDepartment of Pediatrics, MacKay Children’s HospitalDepartment of Pediatrics, MacKay Children’s HospitalDepartment of Pediatrics, Hsinchu MacKay Memorial HospitalDepartment of Pediatrics, MacKay Children’s HospitalDepartment of Pediatrics, MacKay Children’s HospitalAbstract Background Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive disease characterized by the combination of glomerulopathy with early-onset nephrotic syndrome and microcephaly with central nervous system anomalies. Given its clinical heterogeneity, GAMOS is believed to be a genetically heterogenous group of disorders. Recently, it has been reported that mutations in KEOPS-encoding genes, including the OSGEP gene, were responsible for GAMOS. Results Overall, 6 patients from 5 different Taiwanese families were included in our study; the patients had an identical OSGEP gene mutation (c.740G > A transition) and all exhibited a uniform clinical phenotype with early-onset nephrotic syndrome, craniofacial and skeletal dysmorphism, primary microcephaly with pachygyria, and death before 2 years of age. We reviewed their clinical manifestations, the prenatal and postnatal presentations and ultrasound findings, results of imaging studies, associated anomalies, and outcome on follow-up. All individuals were found to have an “aged face” comprising peculiar facial dysmorphisms. Arachnodactyly or camptodactyly were noted in all patients. Neurological findings consisted of microcephaly, hypotonia, developmental delay, and seizures. Brain imaging studies all showed pachygyria and hypomyelination. All patients developed early-onset nephrotic syndrome. The proteinuria was steroid-resistant and eventually resulted in renal function impairment. Prenatal ultrasound findings included microcephaly, intrauterine growth restriction, and oligohydramnios. Fetal MRI in 2 patients confirmed the gyral and myelin abnormalities. Conclusions Our study suggests that a careful review of the facial features can provide useful clues for an early and accurate diagnosis. Prenatal ultrasound findings, fetal MRI, genetic counseling, and mutation analysis may be useful for an early prenatal diagnosis.http://link.springer.com/article/10.1186/s13023-018-0961-9Galloway-Mowat syndromeOSGEPKEOPSNephrotic syndromeMicrocephalyPachygyria |
| spellingShingle | Pei-Yi Lin Min-Hua Tseng Martin Zenker Jia Rao Friedhelm Hildebrandt Shih-Hua Lin Chun-Chen Lin Jui-Hsing Chang Chyong-Hsin Hsu Ming-Dar Lee Shuan-Pei Lin Jeng-Daw Tsai Galloway-Mowat syndrome in Taiwan: OSGEP mutation and unique clinical phenotype Orphanet Journal of Rare Diseases Galloway-Mowat syndrome OSGEP KEOPS Nephrotic syndrome Microcephaly Pachygyria |
| title | Galloway-Mowat syndrome in Taiwan: OSGEP mutation and unique clinical phenotype |
| title_full | Galloway-Mowat syndrome in Taiwan: OSGEP mutation and unique clinical phenotype |
| title_fullStr | Galloway-Mowat syndrome in Taiwan: OSGEP mutation and unique clinical phenotype |
| title_full_unstemmed | Galloway-Mowat syndrome in Taiwan: OSGEP mutation and unique clinical phenotype |
| title_short | Galloway-Mowat syndrome in Taiwan: OSGEP mutation and unique clinical phenotype |
| title_sort | galloway mowat syndrome in taiwan osgep mutation and unique clinical phenotype |
| topic | Galloway-Mowat syndrome OSGEP KEOPS Nephrotic syndrome Microcephaly Pachygyria |
| url | http://link.springer.com/article/10.1186/s13023-018-0961-9 |
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