Researchers identify new syndrome leading to intersex

Hudson Institute sex genetics experts Professor Vincent Harley and Dr Stefan Bagheri-Fam have led an international study which identifies a new rare disorder that forms another piece of the puzzle in understanding why some people are born intersex.

People who are intersex have reproductive organs, sexual anatomy or chromosome patterns that do not fit the typical definition of male (XY) or female (XX).

The study, published in the journal, Human Molecular Genetics, shows how a mutated form of the FGFR2 gene, already known to cause craniosynostosis (where the joints between the bones of a baby’s skull close before it is fully formed), can also cause XY sex reversal.

The study identifies a new intersex syndrome, called Craniosynostosis with Sex Reversal (CSR).

“The umbrella term ‘intersex’ has many genetic causes, the majority of which go undiagnosed,” Professor Harley said.

“Our team has identified how a mutation in the FGFR2 gene can concurrently cause craniosynostosis and XY sex reversal and as a result, we have identified a new syndrome called CSR.”

Researchers analysed genetic data from a German patient who, as a teenager, was diagnosed with the form of intersex called XY gonadal dysgenesis.

Genetic sequencing revealed that the patient carried the mutated FGFR2 gene, already a known cause of craniosynostosis.

The question remained whether the FGFR2 mutation was also responsible for the XY male-to-female sex reversal. The breakthrough came when Hudson scientist and lead author of the paper, Dr Stefan Bagheri-Fam, working with Yale University researchers studied mice with a very similar mutation.

“One to two per cent of live births are intersex, which can result in psychological trauma, infertility, lifelong endocrine care, multiple surgeries and increased risk of conditions like gonadal cancer,” Professor Harley said.

“By identifying the genetic causes, clinicians are better equipped to precisely treat and manage the health risks and conditions associated with specific genetic intersex conditions.