Abstract
INTRODUCTION: Witteveen-Kolk syndrome (WITKOS, OMIM 613406) is a rare autosomal dominant neurodevelopmental disorder caused by heterozygous loss-of-function variants in the SIN3A gene or microdeletions involving SIN3A at 15q24. We aimed to present new clinical and genetic findings of 2 patients diagnosed with WITKOS. CASE PRESENTATION: This study presents 2 cases: patient 1 had genomic variations caused by a multilocus disease, including pathogenic variations in the SIN3A gene and paternal mosaic uniparental disomy 11 (UPD(11)p), and showed syndromic symptoms. Patient 2 was followed up with a preliminary diagnosis of hypogonadotropic hypogonadism (HH) and a new de novo pathogenic variation in the SIN3A gene. CONCLUSIONS: These findings expand the phenotypic spectrum associated with SIN3A variants and highlight the importance of comprehensive genetic testing in atypical presentations of rare diseases. The inclusion of SIN3A in HH gene panels may aid molecular diagnosis in cases without apparent syndromic findings. This study contributes to the understanding of the phenotypic and genotypic heterogeneity of WITKOS.