First African case report of hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome due to inverted duplication and deletion of chromosome 10p
Abstract Background Hypoparathyroidism, sensorineural deafness and renal disease (HDR) syndrome, also known as Barakat syndrome, is a rare autosomal dominant genetic disorder manifesting as a result of haploinsufficiency of the GATA3 gene. GATA3 is a member of zinc-finger transcription factors that...
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SpringerOpen
2024-12-01
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| Series: | Egyptian Journal of Medical Human Genetics |
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| Online Access: | https://doi.org/10.1186/s43042-024-00619-x |
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| author | Tumelo M. Satekge Glenrose Rikhotso Bianca Rossouw Bronwyn Dillon Fiona Baine-Savanhu |
| author_facet | Tumelo M. Satekge Glenrose Rikhotso Bianca Rossouw Bronwyn Dillon Fiona Baine-Savanhu |
| author_sort | Tumelo M. Satekge |
| collection | DOAJ |
| description | Abstract Background Hypoparathyroidism, sensorineural deafness and renal disease (HDR) syndrome, also known as Barakat syndrome, is a rare autosomal dominant genetic disorder manifesting as a result of haploinsufficiency of the GATA3 gene. GATA3 is a member of zinc-finger transcription factors that are responsible for the embryonic development of key organs and structures including the parathyroid glands, auditory system and kidneys. Here, we report the first African case of HDR syndrome to be confirmed by chromosomal microarray analysis (CMA). Case presentation A 3-month-old female presented with focal seizures due to severe hypocalcaemia associated with low parathyroid hormone. The patient also had sensorineural hearing loss, global developmental delay and prominent dysmorphic features that included a tall, prominent forehead, long, curly eyelashes, a depressed nasal bridge as well as subtle skeletal abnormalities. The dysmorphic features, global developmental delay and hypoparathyroidism associated with persistent and severe hypocalcaemia led to the investigation by CMA which detected a 9.5 Mb heterozygous terminal loss of chromosome 10p15.3p14; GATA3 is included in this region. In addition, CMA detected a 4.4 Mb heterozygous interstitial gain of chromosome 10p14p13 indicating the presence of an inverted duplication and deletion of chromosome 10p. The patient was actively treated with IVI calcium gluconate, oral calcium carbonate and alfa cholecalciferol. Conclusion This case emphasizes that complex patients with developmental delay and multiple congenital anomalies are likely to benefit from evaluation by CMA. Indeed, this approach still has an important role to play, particularly in inadequately resourced settings such as in Africa, for the investigation of patients with complex genetic disorders associated with significant chromosome aberrations. |
| format | Article |
| id | doaj-art-798bb5517a9444e1bc145e78694a1e2f |
| institution | Kabale University |
| issn | 2090-2441 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Egyptian Journal of Medical Human Genetics |
| spelling | doaj-art-798bb5517a9444e1bc145e78694a1e2f2025-01-05T12:32:21ZengSpringerOpenEgyptian Journal of Medical Human Genetics2090-24412024-12-012511710.1186/s43042-024-00619-xFirst African case report of hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome due to inverted duplication and deletion of chromosome 10pTumelo M. Satekge0Glenrose Rikhotso1Bianca Rossouw2Bronwyn Dillon3Fiona Baine-Savanhu4Division of Chemical Pathology, School of Medicine, National Health Laboratory Service, University of LimpopoDepartment of Paediatrics and Child Health, Pietersburg Hospital, Limpopo Department of Health, University of LimpopoDivision of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the WitwatersrandDivision of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the WitwatersrandDivision of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the WitwatersrandAbstract Background Hypoparathyroidism, sensorineural deafness and renal disease (HDR) syndrome, also known as Barakat syndrome, is a rare autosomal dominant genetic disorder manifesting as a result of haploinsufficiency of the GATA3 gene. GATA3 is a member of zinc-finger transcription factors that are responsible for the embryonic development of key organs and structures including the parathyroid glands, auditory system and kidneys. Here, we report the first African case of HDR syndrome to be confirmed by chromosomal microarray analysis (CMA). Case presentation A 3-month-old female presented with focal seizures due to severe hypocalcaemia associated with low parathyroid hormone. The patient also had sensorineural hearing loss, global developmental delay and prominent dysmorphic features that included a tall, prominent forehead, long, curly eyelashes, a depressed nasal bridge as well as subtle skeletal abnormalities. The dysmorphic features, global developmental delay and hypoparathyroidism associated with persistent and severe hypocalcaemia led to the investigation by CMA which detected a 9.5 Mb heterozygous terminal loss of chromosome 10p15.3p14; GATA3 is included in this region. In addition, CMA detected a 4.4 Mb heterozygous interstitial gain of chromosome 10p14p13 indicating the presence of an inverted duplication and deletion of chromosome 10p. The patient was actively treated with IVI calcium gluconate, oral calcium carbonate and alfa cholecalciferol. Conclusion This case emphasizes that complex patients with developmental delay and multiple congenital anomalies are likely to benefit from evaluation by CMA. Indeed, this approach still has an important role to play, particularly in inadequately resourced settings such as in Africa, for the investigation of patients with complex genetic disorders associated with significant chromosome aberrations.https://doi.org/10.1186/s43042-024-00619-xHypoparathyroidismSensorineural deafness and renal disease syndromeBarakat syndromeChromosomal microarrayGATA3 |
| spellingShingle | Tumelo M. Satekge Glenrose Rikhotso Bianca Rossouw Bronwyn Dillon Fiona Baine-Savanhu First African case report of hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome due to inverted duplication and deletion of chromosome 10p Egyptian Journal of Medical Human Genetics Hypoparathyroidism Sensorineural deafness and renal disease syndrome Barakat syndrome Chromosomal microarray GATA3 |
| title | First African case report of hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome due to inverted duplication and deletion of chromosome 10p |
| title_full | First African case report of hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome due to inverted duplication and deletion of chromosome 10p |
| title_fullStr | First African case report of hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome due to inverted duplication and deletion of chromosome 10p |
| title_full_unstemmed | First African case report of hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome due to inverted duplication and deletion of chromosome 10p |
| title_short | First African case report of hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome due to inverted duplication and deletion of chromosome 10p |
| title_sort | first african case report of hypoparathyroidism deafness and renal dysplasia hdr syndrome due to inverted duplication and deletion of chromosome 10p |
| topic | Hypoparathyroidism Sensorineural deafness and renal disease syndrome Barakat syndrome Chromosomal microarray GATA3 |
| url | https://doi.org/10.1186/s43042-024-00619-x |
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