Background: A 60-day-old infant with genital ambiguity was assessed in the multidisciplinary urogenital clinic. The baby was born full term and weighed 3.4 kg at birth. The antenatal history was noncontributory. On physical examination, there was no obvious dysmorphic features. On genitourinary exam, there was a well developed scrotum that was bifid, with rugae and pigmentation. There was penoscrotal transposition. His phallus was of a normal breadth and length with ventral curvature. In addition there was hypospadias at the base of the phallus. Both testes were palpable in the scrotum.
Objective and hypotheses: Given the mild to moderately undervirilised male, the clinical impression was idiopathic isolated severe hypospadias.
Method: This is a case report of an interesting and rare case with genetic confirmation.
Results: Laboratory workup included an LH of 1.3 IU/l (0.14.8 IU/l), FSH 2.0 IU/l (015 IU/l), and testosterone level was 3.7 nmol/l normal for age is <16.0 nmol/l. Surprisingly, further testing revealed a 46,XX karyotype and FISH for SRY was negative. Genomic microarray analysis showed a copy number gain in chromosome region Xq27.1. This region contains the SRY related HMG box-containing gene 3 (SOX3) gene. SOX3 is a single exon gene located in a highly conserved region of the X-chromosome. It is a transcription factor, encodes a protein that is most similar to SRY.
Conclusion: The clinical significance of duplication of the SOX3 locus in 46,XX individual is currently unclear, however a recent report suggested that copy number changes within this genomic region may be associated with 46,XX sex reversal. Further investigation of this copy number gain is in progress.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology