For patients with rare genetic diseases, receiving a diagnosis often opens the door to much better clinical management and potential treatments. Unfortunately, the vast majority of these patients remain undiagnosed. The Syndromes Without a Name Clinic at the University of Cardiff was established to shorten the long diagnostic odyssey of patients with rare and undiagnosed diseases.
When the clinic was founded, they established a set of acceptance criteria to ensure that their patients’ diseases were likely to be genetic. They are based at Cardiff’s University Hospital, the largest hospital in Wales, which provides them with numerous samples and access to clinicians and researchers.
The clinic multidisciplinary team (MDT) meets weekly to discuss patients, their history, and genetic variants that the team has identified. Their strength lies in the diverse range of specialties of the group and their collaborative approach. The clinical team meet with patients face-to-face twice a week for re-evaluations which help to build a phenotypic picture.
The genomic reanalysis process begins when a patient is referred to the SWAN clinic after negative routine genetic testing. The clinic reanalyses existing genomic data using advanced software, such as Congenica, to identify potential pathogenic variants. This process involves collaboration with clinical genetics laboratories to confirm any findings before reporting them to patients and their families.
Williams presented an example of a case from their paediatric clinic that resulted in a diagnosis. The patient had previously gone through genomic sequencing which had resulted in the identification of two intronic variants. These variants were difficult to functionally characterise as markers of a particular rare disease; however, it was recognised that the gene was related to the phenotype.
Collaborating with researchers at the University of Southampton who sequenced the RNA of the aberrant gene, the transcript confirmed alternative deleterious splicing. Furthermore, they found that this was a compound heterozygous genetic event stemming from both parents. This led to the patient’s diagnosis.
