A Novel De Novo KDM3B Variant in the Youngest Reported Male Patient With Diets-Jongmans Syndrome and Facial Asymmetry.

KDM3B encodes a histone lysine demethylase and is involved in transcriptional regulation. Patients with heterozygous pathogenic variants in KDM3B are diagnosed with Diets-Jongmans syndrome (DIJOS), a rare autosomal dominant disorder characterized by intellectual disability, developmental delay, distinctive facial features, and short stature. Here, we report the identification of a novel frameshift variant in KDM3B in a seven-month-old male patient evaluated for small stature, microcephaly, facial asymmetry, and mild gross motor delays. A trio exome with results at 14 months of age identified a de novo pathogenic variant in KDM3B, c.2446del p.(Ser816Valfs*6). At 15 months of age, the patient demonstrated additional clinical findings of mild bilateral epicanthal folds, short philtrum, mildly downslanting palpebral fissures, broad nasal bridge, and mildly simplified ears, while his physical and behavioral development remained age appropriate. This is the youngest known patient with a de novo KDM3B variant identified before 1 year of age. Unlike other DIJOS patients, the current proband does not have signs of significant neurodevelopmental delay. Additionally, he has unilateral facial asymmetry, which had not been previously reported in DIJOS patients. This patient's unique and evolving clinical features further our understanding of the phenotypic diversity and may inform the long-term prognosis of DIJOS.