Published: 28 February 2020
Dr Alison Foster is an Academic Clinical Research Fellow Registrar in Clinical Genetics in the Institute of Cancer and Genomic Sciences at the University of Birmingham. As chief investigator of The Phenotyping of Overgrowth Disorders (POD) study she explains how a better understanding of rare and complex disorders can improve care for patients with rare disease.
I am the chief investigator of The Phenotyping of Overgrowth Disorders (POD) study. Funded by NIHR, the study aims to address the need for a group of rare and complex genetic conditions that affect many different aspects of life and health.
POD investigates a group of rare genetic conditions associated with increased growth. Patients often experience a wide range of health issues which may include congenital anomalies, intellectual disability, and sometimes an increased risk of childhood tumours. I became interested in this area through my training in Clinical Genetics and meeting many patients and families with these disorders. Diagnoses can often be hard to come by for patients with rare disease. Many families are in the difficult position of not having a name for their child’s condition, not having any information about what problems might occur, or what treatments might help.
Sometimes genetic testing can help in diagnosing rare disorders. But for many rare conditions, especially those that are newly discovered, there isn’t much information known about them yet. There is a real need to study rare disorders to find out the range of problems that occur or might develop in childhood or later life.
Overgrowth disorders are associated with a wide range of phenotypes (features) including increased height or head size, congenital anomalies, developmental delay, autism spectrum disorder, and medical problems such as scoliosis or the development of tumours in childhood. The POD study aims to capture a really detailed and accurate picture of each participant and their medical problems to increase understanding of overgrowth disorders.
The POD study also undertakes detailed genomic testing. This helps to identify associations between different variants in genes and the medical problems that might occur. It also gives insight into the molecular pathways involved, and ultimately potentially identifies targets for personalised treatments.
To explain how the POD study works in practice, here is an example of the sorts of activity we carry out. A child was diagnosed with a very rare disorder through taking part in the study. By studying the phenotype of this child we were able to identify another individual with the same disorder. In collaboration with international colleagues, we identified that abnormal blood vessels are a feature of this condition and there is an associated risk of these blood vessels rupturing with serious consequences such as stroke.
This research has translated into clinical care and we now perform investigations to look at the blood vessels in these patients. There are existing licensed drugs that target the pathway this gene is involved in, so treatment is a very real and exciting prospect for the near future.
Working to better understand these complex disorders and how we can improve care for patients with rare disease is hugely rewarding. I'm very grateful to the NIHR Rare Disease Translational Research Collaboration who funded my doctoral fellowship and made this study possible.
- Dr Alison Foster, Academic Clinical Research Fellow Registrar in Clinical Genetics, Institute of Cancer and Genomic Sciences, University of Birmingham.