Genetics in medicine : official journal of the American College of Medical Genetics · 2024
Severe neurodevelopmental phenotype, diagnostic, and treatment challenges in patients with SECISBP2 deficiency.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
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Stoupa Athanasia, Franca Monica Malheiros, Abdulhadi-Atwan Maha, Fujisawa Haruki, Korwutthikulrangsri Manassawee, Marchand Isis, Polak Gabrielle, Beltrand Jacques, Polak Michel, Kariyawasam Dulanjalee, Liao Xiao-Hui, Raimondi Chantalle, Steigerwald Connolly, Abreu Nicolas J, Bauer Andrew J, Carré Aurore, Taneja Charit, Mekhoubad Allison Bauman, Dumitrescu Alexandra M
Аннотация
PURPOSE: 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.
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.