Expanding the clinical spectrum of pathogenic variation in NR2F2: Asplenia

We present a case with congenital syndromic asplenia associated with immune deficiency, glandular hypospadias and cryptorchidism. Genetic analysis identified a likely pathogenic de novo variant in NR2F2. Pathogenic NR2F2 variants have been associated with other congenital anomalies affecting the central axis, such as congenital heart disease and diaphragmatic hernia, which were not part of our patient's clinical features. The association between NR2F2 and asplenia (including glandular hypospadias and cryptorchidism) has been described in animal models and our report is the first expanding the NR2F2 clinical spectrum in humans to include asplenia.

Automated summary

This case report presents a rare syndrome of congenital syndromic asplenia associated with immune deficiency, glandular hypospadias, and cryptorchidism, with a likely pathogenic de novo variant in the NR2F2 gene identified through genetic analysis. The study expands the clinical spectrum of NR2F2 in humans to include asplenia, with previous associations in animal models.