Endocrine Abstracts

Background: Disorders of sex development (DSDs), or atypical genitalia in newborns, are heterogeneous in origin and require early, ongoing involvement of a specialist multidisciplinary team (MDT) to ensure timely diagnosis and management.

Case Summary: We present the case of a term infant born with perineal hypospadias and bilateral cryptorchidism. Initial investigations revealed a 46, XY karyotype, normal testosterone (8.04 nmol/l), and undetectable 17-hydroxyprogesterone (<1.6 nmol/l), thereby reducing the likelihood of any underlying endocrine abnormalities. Parents were counselled that genital surgery would be required in stages, but no other major concerns were expected. Over the following months, he developed persistent vomiting, faltering growth, and periorbital puffiness in the morning. These symptoms were initially attributed to gastro oesophageal reflux, cow’s milk protein allergy, and nasolacrimal duct obstruction. At 5 months, he presented with generalised oedema and anuria and further investigations revealed end-stage kidney disease. Genetic testing identified a heterozygous pathogenic mutation in the WT1 gene, confirming a WT1-related disorder and congenital nephrotic syndrome. Management involved the commencement of peritoneal dialysis, plans for bilateral nephrectomy and renal transplantation, alongside surgical correction of hypospadias and cryptorchidism. Surveillance for Wilms tumour was also initiated in line with protocols for WT1-related conditions. The diagnosis was made only after clinical features suggestive of renal failure became evident. In retrospect, no urine dipstick test was performed at birth, and a raised creatinine was “attributed to maternal levels”. There was also a delay in communicating the genetic result, which had been requested earlier.

Discussion: This case reinforces the importance of considering broader differential diagnosis in newborns with atypical genitalia with 46,XY DSD. A thorough and systematic evaluation of infants with atypical genitalia is essential to avoid missed diagnoses that may have significant consequences. Early genetic assessment plays a key role in guiding appropriate management.