Stoupa A.Franca M.M.Abdulhadi-Atwan M.Fujisawa H.Korwutthikulrangsri M.Marchand I.Polak G.Beltrand J.Polak M.Kariyawasam D.Liao X.H.Raimondi C.Steigerwald C.Abreu N.J.Bauer A.J.Carré A.Taneja C.Mekhoubad A.B.Dumitrescu A.M.Mahidol University2024-11-062024-11-062024-12-01Genetics in Medicine Vol.26 No.12 (2024)10983600https://repository.li.mahidol.ac.th/handle/20.500.14594/101890Purpose: Defects in the gene encoding selenocysteine insertion sequence binding protein 2, SECISBP2, result in global impaired selenoprotein synthesis manifesting a complex syndrome with characteristic serum thyroid function tests due to impaired thyroid hormone metabolism. Knowledge about this multisystemic defect remains limited. Methods: Genetic and laboratory investigations were performed in affected members from 6 families presenting with short stature and failure to thrive. Results: Four probands presented a complex neurodevelopmental profile, including absent speech, autistic features, and seizures. Pediatric neurological evaluation prompted genetic investigations leading to the identification of SECISBP2 variants before knowing the characteristic thyroid tests in 2 cases. Thyroid hormone treatment improved motor development, whereas speech and intellectual impairments persisted. This defect poses great diagnostic and treatment challenges for clinicians, as illustrated by a case that escaped detection for 20 years because SECISBP2 was not included in the neurodevelopmental genetic panel, and his complex thyroid status prompted antithyroid treatment instead. Conclusion: This syndrome uncovers the role of selenoproteins in humans. The severe neurodevelopmental disabilities manifested in 4 patients with SECISBP2 deficiency highlight an additional phenotype in this multisystem disorder. Early diagnosis and treatment are required, and long-term evaluation will determine the full spectrum of manifestations and the impact of therapy.MedicineArticleSCOPUS10.1016/j.gim.2024.1012802-s2.0-852076395581530036639315526