No abstract

Purpose In addition to environmental causes such as TORCH infection, trauma and drug or chemical exposure, childhood cataracts (CC) frequently have a genetic basis. They may be isolated or syndromic and have been associated with mutations in over 110 genes. We have recently demonstrated that nextgeneration sequencing (NGS), a high throughput sequencing technique that enables the parallel sequencing of multiple genes, is ideally suited to the investigation of bilateral CC. This study assesses the diagnostic outcomes of traditional routine investigations and compares this with outcomes of NGS testing. Methods A retrospective review of the medical records of 27 consecutive patients with bilateral CC presenting in 2010-2012 was undertaken. The outcomes of routine investigations in these patients, including TORCH screen, urinalysis, karyotyping, and urinary and plasma organic amino acids, were collated. The success of routine genetic investigations undertaken over 10 years (2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010) was also assessed. Results By April 2014, the underlying cause of bilateral CC had been identified in just one of 27 patients despite 44% (n = 12) receiving a full 'standard' investigative work-up and 22% (n = 6) investigations in addition to the standard work-up. Fifteen of these patients underwent NGS testing and nine (60%) of these received a diagnosis for their CC. Conclusion The frequency of patients receiving a diagnosis for their CC after standard care and the time taken to diagnosis was disappointing. NGS testing improved diagnostic rates and time to diagnosis, as well as changing clinical management. These data serve as a baseline for future evaluation of novel diagnostic modalities.