Partial gonadal dysgenesis associated with a pathogenic variant of PBX1 transcription factor

A term neonate was admitted to the Neonatal Intensive Care Unit for respiratory distress, hypotonia and atypical genitalia. Significant findings included a small phallic structure, labial folds, no palpable gonads and two perineal openings. Pelvic ultrasound showed uterine didelphys and a gonad in the right inguinal canal. The right gonad was removed during diagnostic laparoscopy with microscopic evaluation showing infantile testicular tissue and fluorescence in-situ hybridisation showed only XY signal suggesting that the removed gonad was a male-developed testis. Infant was 46,XY, SRY probe positive. The parents chose a female sex assignment prior to gonadectomy. The infant had respiratory insufficiency and central hypotonia that persisted on discharge. Whole exome sequencing showed a heterozygous pathogenic variant of the PBX1 gene. This variant encodes the pre-B-cell leukaemia homeobox PBX transcription factor and has been associated with malformations and severe hypoplasia or aplasia of multiple organs including lungs and gonads. Whole exome sequencing was crucial in providing a unifying diagnosis for this patient.