Severe neurodevelopmental phenotype, diagnostic and treatment challenges in patients with SECISBP2 deficiency
Authors
Athanasia Stoupa, Pediatric Endocrinology, Gynecology and Diabetology Department, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France; Cochin Institute, Paris, and IMAGINE Institute affiliate, Paris, Université Paris Cité, France.
Monica Malheiros Franca, Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
Maha Abdulhadi-Atwan, Pediatric Endocrinology Department, Palestine Red Crescent Society Hospital, Hebron branch, Bethlehem, Palestine.
Haruki Fujisawa, Department of Medicine, The University of Chicago, Chicago, Illinois, USA; Department of Endocrinology and Metabolism, Fujita Health University, Toyoake, Japan.
Manassawee Korwutthikulrangsri, Department of Medicine, The University of Chicago, Chicago, Illinois, USA; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Isis Marchand, Pediatric Department, Hôpital Intercommunal de Créteil, Créteil, France.
Gabrielle Polak, Faculté de Médecine, Université Paris Cité, Paris, France.
Jacques Beltrand, Pediatric Endocrinology, Gynecology and Diabetology Department, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France; Cochin Institute, Paris, and IMAGINE Institute affiliate, Paris, Université Paris Cité, France.
Michel Polak, Pediatric Endocrinology, Gynecology and Diabetology Department, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France; Cochin Institute, Paris, and IMAGINE Institute affiliate, Paris, Université Paris Cité, France; Centre de référence des maladies endocriniennes rares de la croissance et du développement, Hôpital Universitaire Necker-Enfants Malades, Paris, France; Centre régional de dépistage néonatal (CRDN) Ile de France, Paris, France.
Dulanjalee Kariyawasam, Pediatric Endocrinology, Gynecology and Diabetology Department, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France; Cochin Institute, Paris, and IMAGINE Institute affiliate, Paris, Université Paris Cité, France.
Xiao-Hui Liao, Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
Chantalle Raimondi, Advocate Health - MidwestFollow
Connolly Steigerwald, Department of Neurology, NYU Grossman School of Medicine, New York, USA.
Nicolas J. Abreu, Department of Neurology, NYU Grossman School of Medicine, New York, USA.
Andrew J. Bauer, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Pennsylvania, USA.
Aurore Carré, Cochin Institute, Paris, and IMAGINE Institute affiliate, Paris, Université Paris Cité, France.
Charit Taneja, Division of Endocrinology, Diabetes and Metabolism, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY.
Allison Bauman Mekhoubad, Division of Pediatric Endocrinology, Northwell Health, Cohen Children's Medical Center, Lake Success, NY, USA.
Alexandra M. Dumitrescu, Department of Medicine, The University of Chicago, Chicago, Illinois, USA; Committee of Molecular Metabolism and Nutrition, The University of Chicago, Chicago, Illinois, USA. Electronic address: alexd@uchicago.edu.
Recommended Citation
Stoupa A, Franca MM, Abdulhadi-Atwan M, et al. Severe neurodevelopmental phenotype, diagnostic, and treatment challenges in patients with SECISBP2 deficiency. Genet Med. 2024;26(12):101280. doi:10.1016/j.gim.2024.101280
Abstract
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 six families presenting with short stature, 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 two cases. Thyroid hormone treatment improved motor development, while speech and intellectual impairments persisted. This defect poses great diagnostic and treatment challenges for clinicians, as illustrated by a case that escaped detection for 20years, as SECISBP2 was not included in the neurodevelopmental genetic panel, and his complex thyroid status prompted anti-thyroid treatment instead.
Conclusion: This syndrome uncovers the role of selenoproteins in humans. The severe neurodevelopmental disabilities manifested in four 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.
Affiliations
Advocate Children's Hospital