First Report of a Novel Variant Linked to Weiss-Kruszka Syndrome and Congenital Diaphragmatic Hernia: Insights into Potential Additional Malformations.

INTRODUCTION

Weiss-Kruszka syndrome is a rare, autosomal dominant neurodevelopmental disorder caused by pathogenic variants in the , located at chromosome 9p31.2. Clinically, it is characterized by craniofacial dysmorphism, global developmental delay, intellectual disability, short stature, congenital anomalies of the heart and brain, and feeding difficulties. The phenotypic spectrum is notably heterogeneous, with variable expressivity and occasional incomplete penetrance.

CASE PRESENTATION

Herein, we report a novel de novo heterozygous frameshift variant in , designated c.2924del; p.(Gln975ArgfsTer3) (NM_021224.6), identified in a pediatric patient.

CONCLUSION

Importantly, our patient presented with a congenital diaphragmatic hernia - an anomaly not previously described in association with Weiss-Kruszka syndrome. To date, 48 cases have been reported in the literature. Our findings further broaden the phenotypic spectrum linked to variants and emphasize the need for continued clinical and molecular characterization. Through the detailed documentation of this unique case, we aimed to enhance the understanding of the clinical variability and potential comorbidities associated with this emerging syndrome.