Identification of a novel IGSF1 variant in two Malaysian malesiblings with central hypothyroidism and macroorchidism
Introduction IGSF1 mutation is the commonest cause of mild to moderate isolated central congenital hypothyroidism and has an X-linked recessive inheritance, primarily affecting males. Other notable clinical features are macroorchidism with delayed pubertal testosterone rise, large birth weight, incr...
| Main Authors: | , , , , , |
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| Format: | Article |
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Galenos Yayinevi
2024
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| Online Access: | http://psasir.upm.edu.my/id/eprint/116196/ |
| _version_ | 1848866946724921344 |
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| author | Lee, Yee Lin Ting, Tzer Hwu Lim, Chong Teik Thilakavathy, Karuppiah Musa, Nurul Huda Ling, King Hwa |
| author_facet | Lee, Yee Lin Ting, Tzer Hwu Lim, Chong Teik Thilakavathy, Karuppiah Musa, Nurul Huda Ling, King Hwa |
| author_sort | Lee, Yee Lin |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Introduction IGSF1 mutation is the commonest cause of mild to moderate isolated central congenital hypothyroidism and has an X-linked recessive inheritance, primarily affecting males. Other notable clinical features are macroorchidism with delayed pubertal testosterone rise, large birth weight, increased body mass index, low prolactin, transient growth hormone deficiency and low prolactin. Case Presentation Two male siblings with central hypothyroidism were found to have a novel IGSF1 c.3467T>A variant that was likely pathogenic based on the family segregation study. The proband, aged 3 years presented at 18 days old with prolonged jaundice while his 16-year-old brother was only detected to have central hypothyroidism after the proband’s genetic analysis result was known. Both siblings were obese, had large birth weights, macroorchidism and low prolactin. The proband’s brother had intellectual disability while the proband had normal development. Conclusion This case study highlights the importance of evaluation for the IGSF1 variant in patients with unexplained central hypothyroidism, especially when accompanied by X-linked inheritance and macroorchidism. Family segregation analysis allows detection of other affected family members or carriers who may also benefit from thyroxine treatment. |
| first_indexed | 2025-11-15T14:28:41Z |
| format | Article |
| id | upm-116196 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-15T14:28:41Z |
| publishDate | 2024 |
| publisher | Galenos Yayinevi |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1161962025-03-20T04:40:52Z http://psasir.upm.edu.my/id/eprint/116196/ Identification of a novel IGSF1 variant in two Malaysian malesiblings with central hypothyroidism and macroorchidism Lee, Yee Lin Ting, Tzer Hwu Lim, Chong Teik Thilakavathy, Karuppiah Musa, Nurul Huda Ling, King Hwa Introduction IGSF1 mutation is the commonest cause of mild to moderate isolated central congenital hypothyroidism and has an X-linked recessive inheritance, primarily affecting males. Other notable clinical features are macroorchidism with delayed pubertal testosterone rise, large birth weight, increased body mass index, low prolactin, transient growth hormone deficiency and low prolactin. Case Presentation Two male siblings with central hypothyroidism were found to have a novel IGSF1 c.3467T>A variant that was likely pathogenic based on the family segregation study. The proband, aged 3 years presented at 18 days old with prolonged jaundice while his 16-year-old brother was only detected to have central hypothyroidism after the proband’s genetic analysis result was known. Both siblings were obese, had large birth weights, macroorchidism and low prolactin. The proband’s brother had intellectual disability while the proband had normal development. Conclusion This case study highlights the importance of evaluation for the IGSF1 variant in patients with unexplained central hypothyroidism, especially when accompanied by X-linked inheritance and macroorchidism. Family segregation analysis allows detection of other affected family members or carriers who may also benefit from thyroxine treatment. Galenos Yayinevi 2024 Article PeerReviewed Lee, Yee Lin and Ting, Tzer Hwu and Lim, Chong Teik and Thilakavathy, Karuppiah and Musa, Nurul Huda and Ling, King Hwa (2024) Identification of a novel IGSF1 variant in two Malaysian malesiblings with central hypothyroidism and macroorchidism. Journal of Clinical Research in Pediatric Endocrinology. ISSN 1308-5727; eISSN: 1308-5735 https://jcrpe.org/articles/doi/jcrpe.galenos.2024.2023-12-1 10.4274/jcrpe.galenos.2024.2023-12-1 |
| spellingShingle | Lee, Yee Lin Ting, Tzer Hwu Lim, Chong Teik Thilakavathy, Karuppiah Musa, Nurul Huda Ling, King Hwa Identification of a novel IGSF1 variant in two Malaysian malesiblings with central hypothyroidism and macroorchidism |
| title | Identification of a novel IGSF1 variant in two Malaysian malesiblings with central hypothyroidism and macroorchidism |
| title_full | Identification of a novel IGSF1 variant in two Malaysian malesiblings with central hypothyroidism and macroorchidism |
| title_fullStr | Identification of a novel IGSF1 variant in two Malaysian malesiblings with central hypothyroidism and macroorchidism |
| title_full_unstemmed | Identification of a novel IGSF1 variant in two Malaysian malesiblings with central hypothyroidism and macroorchidism |
| title_short | Identification of a novel IGSF1 variant in two Malaysian malesiblings with central hypothyroidism and macroorchidism |
| title_sort | identification of a novel igsf1 variant in two malaysian malesiblings with central hypothyroidism and macroorchidism |
| url | http://psasir.upm.edu.my/id/eprint/116196/ http://psasir.upm.edu.my/id/eprint/116196/ http://psasir.upm.edu.my/id/eprint/116196/ |