Abstract

Background: Pathogenic variants inKDM3Bhave been implicated as the cause of Diets-Jongmans syndrome (DIJOS), an autosomal-dominant disorder characterized by growth retardation, intellectual disability, facial dysmorphism and autism-spectrum disorder. However, only a limited number of cases have been reported. Methods: The general characteristics of four patients were recorded, including clinical features, child development, neuropsychological assessment and therapeutic interventions. Whole exome sequencing (WES) was performed for potential genetic causes and interpretation of variants was performed in accordance with ACMG guidelines. Results: All patients carried de novo variants in theKDM3Bgene, namely, c.2832-3C>G, c.1188del p.(Glu397Argfs*21), c.4580T>C p.(Leu1527Pro), and c.3220dup p.(Glu1074Glyfs*48). Unlike other patients with DIJOS who presented with growth retardation, mild to moderate intellectual developmental disorder and facial dysmorphism, our patients mainly presented with growth retardation, while their neurodevelopment was either normal or mildly impaired. In addition, our patients received primarily supportive care. One patient treated with recombinant human growth hormone (rhGH) showed improvement in growth. Conclusions: Our results broaden the mutational spectrum ofKDM3B-related disorder and highlight the inter-patient variability of the clinical phenotype. For the first time, we demonstrate that rhGH therapy can partially promote growth, providing novel evidence for genetic counseling.