Differences of sex development
When a child has DSD, their sex organs develop differently to other children. This is also sometimes called ‘intersex variations’ or ‘variations in sex characteristics’. There is no consensus on the best terminology when referring to DSD or Intersex variations. For this website, the term DSD will be used as it is the most precise term from a scientific and health perspective.
DSD is an umbrella term used to describe a range of diagnoses, generally identified at birth or at puberty. Types of DSD include hypospadias, ambiguous genitalia, and gonadal dysgenesis.
For some children, it means they have a variation in their genitals, or differences in their hormone production. Others might have delayed puberty or differences in their X or Y chromosomes, reproductive organs, growth and other parts of the body, e.g. heart or kidneys.
DSD presents in a spectrum of ways, for some children and their families this has significant health and psychosocial implications. DSD can also cause infertility and childhood cancers of the testes and ovaries (gonads). DSD can be inherited, but in many cases, there is no clear cause.
Who does it affect?
Who does it affect?
- Uncertainty about a child's sex can be traumatic for the individual, parents and other family members, and can also carry psychological and reproductive consequences for the individual.
- Hypospadias, where the urethra develops abnormally affects in boys one in 250 boys (Andrew Sinclair brilliant minds article
- One in 4500 babies are born with ambiguous genitalia, where an infant's external genitals don't appear to be clearly either male or female (Andrew Sinclair brilliant minds article)
Our DSD research
Our DSD research
DSDs most often occur after a breakdown in the complex genetic network that enables development of testes or ovaries during embryogenesis. Studies have identified a small number of genes that play critical roles in testis and ovary development, but efforts to assemble these into a full regulatory network have yet to be successful, most likely because key pieces of the puzzle are missing.
The Reproductive Development group aims to pool its expertise in human genetics, molecular and developmental biology, to find genes important for testis or ovary development and identify gene changes that cause DSD. We are building strong collaborative ties with researchers and clinicians both nationally and internationally to help achieve this.
Impacts of our research
Impacts of our research
- Using high throughput genomic sequencing, our group has improved diagnostic rates for DSD from a low of 13% to 43% – now implemented in a clinically approved DSD diagnostic test provided nationally and internationally by the Victorian Clinical Genetics Service (VCGS). This test will also reduce the use of other long costly diagnostic procedures.
- Developing a national DSD database which holds detailed clinical information on DSD patients and results of genomic analyses.
- Identifying novel enhancers that regulate expression of the SOX9 testis gene. When duplicated or deleted, these enhancers result in DSD. These enhancers provide a missing link by which SRY regulates SOX9 expression in humans and are a significant cause of DSD.
- We have also identified variants in the genes: NR5A1, SART3, DHH, MAP3K1, DMRT2, NROB2, NFX3 and DVL3 which are responsible for DSD, leading us closer to completing the puzzle of how they can develop.
- We are developing a stem cell-based gonad organoid model in a dish. This will allow us to research how the testis and ovaries develop and how this might be affected in DSD.
We have produced research publications on a number of specific DSDs including: Ambiguous genitalia, Gonadal dysgenesis, Disorders of androgen synthesis or action, Hypospadias, Gonadal regression, Leydig cell hypoplasia, Persistent Müllerian duct syndrome, Cryptorchidism, 46,XX Testicular DSD, Ovotesticular DSD, Müllerian Duct defects, Mayer-Rokitansky-Küster-Hauser syndrome, Dysplastic ovaries, Premature ovarian insufficiency.
Our vision
Our vision
Our mission is to identify the molecular and cellular basis of gonad development and the genetic causes underlying DSDs. We can then apply this knowledge to the diagnosis and clinical management of DSD to improve outcomes for affected children.
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