Chromosomes can sometimes lie

Ahmed Imran Siddiqi,  Ravi Kumar Menon, University College London


Case History

A 29 years old Nigerian man presented with difficulty passing urine and infertility. He had some concerns regarding his low libido and ejaculate was watery and small in volume. He complained of occasional difficulty in maintaining erections. There was no history of trauma, radiation exposure or use of illicit drugs. He had normal pubertal development and secondary sexual features. No family history of relevance.  He had undergone a surgery 12 years ago in Nigeria for hypospadias which was identified at birth. He then moved to UK and started experiencing these symptoms about 2 years ago. His testicular volume was 5 ml bilaterally with curved small penis with chordae and eccentric meatus with fistula. Normal secondary sexual features.


Semen analysis: Azoospermia

FSH 25 IU/L (1.5-12.4); LH 14.9 IU/L (1.7-8.6), Testosterone 8.3 nmol/L (7.6-31.4);

Karyotype analysis: 46 XX; G-band pattern of X chromosome normal. No SRY (sex-determining region on the Y chromosome) of Y chromosome was detected with microdeletion PCR array.  MRI abdomen and pelvis: Mullerian duct remnants in the midline posteriorly. Small gonads in scrotum, small prostate identified. However no uterus or cervix found. No other gonadal tissue identified.  Bone mineral density: DEXA scan Z score Lumbar spine -0.4; Right hip -0.3


The karyotype analysis suggested a rare form of SRY negative 46 XX disorder of sexual development. He was offered counselling. Given the partial gonadal failure and his desire to improve erections and libido, he was started on testosterone replacement. He had corrective surgery for the urethral meatus and penile curvature.


This case illustrates the need to be aware of the causes of such presentation as well as the role of karyotype analysis even in adults. 90% of 46 XX males carry SRY gene translocated to the X chromosome; SRY negative individuals usually have ambiguous genitalia. Only isolated case reports show individuals with normal male genitalia who are SRY negative 46 XX.

Learning points

1.     Importance of Karyotyping in work of infertility and low testosterones.

2.     Rare chromosomal abnormalities can still be diagnosed during adult life.