Addressing the challenges of diagnostic genomics applications for short stature

Dr Dimitar Azmanov

Diagnostic genomics applications for short stature

Dr Dimitar Azmanov from the Department of Diagnostic Genomics, PathWest, was awarded a 2018 Clinician Research Fellowship.

Clinician Research Fellowship

Department of Diagnostic Genomics, PathWest



Dr Dimitar Azmanov is a Genetic Pathologist with the Department of Diagnostic Genomics at PathWest Laboratory Medicine WA.

He was awarded a Clinician Research Fellowship in 2018 to develop a streamlined diagnostic and management process for patients with genetically determined short stature.

Genetic testing has been revolutionised with the introduction of contemporary technological and research advances, yet further work needs to be done towards integrating these cutting-edge methods into standard clinical care. Genetic testing can enhance patient care for children with endocrine disorders. For example, the Australian Growth Hormone Programme uses tailored treatment for patients with short stature if there is a proven genetic component; however, current tests can identify only 5% of the known genetic causes. This project aims to introduce efficient and comprehensive diagnostic tests and associated professional guidelines for management of patients with genetically determined short stature.

Using a genetic analysis technique known as multiple parallel sequencing (MPS), Dr Azmanov demonstrated higher efficacy for detecting underlying abnormality of unexplained prenatal and postnatal growth problems at 19%, which is nearly four times higher than the identification rate of current techniques (chromosomal microarray; 5%).

Currently, chromosomal microarray is funded through Medicare; however, there are strict requirements for the patients who can access the test. The current project confirmed the limited utility of chromosomal microarray in the context of isolated short stature. In turn, the main advancement facilitated by this project is through the introduction of MPS for the investigation of patients with suspected genetically determined short stature. In addition, access to MPS is available through the public health system, which provides equity for all WA patients.

Immediate benefit from this Clinician Research Fellowship project is gained through individualised patient therapy, minimised cost of multiple ongoing investigations, and improved social and genetic counselling support to help inform reproductive decisions in the extended family. Indeed, this research project has re-shaped the patient care for paediatric endocrine patients with suspected major underlying genetic aetiology. Multidisciplinary team (MDT) meetings have been established between the Department of Endocrinology and Diabetes, Perth Children’s Hospital, Genetic Services of Western Australia, and Department of Diagnostic Genomics, PathWest. The MDT meetings have become a forum for discussion of complex cases, interpretation of challenging/unexpected diagnostic genomics results, and integrated care of patients with short stature in WA.

Dr Azmanov’s research has sparked local, national and international collaborations, two published articles with a further three under review, and a successful grant application through the PathWest Innovation scheme to continue his research into translational pathways of diagnostic genomics for developmental disorders.