Splinter K, et al. - Researchers evaluated patients who were referred to the Undiagnosed Diseases Network (UDN), which was established to apply a multidisciplinary model in the evaluation of the most challenging cases and to identify the biologic characteristics of newly discovered diseases. Findings revealed that, although exome sequencing was performed on approximately one-third of the accepted patients prior to referral, the UDN established a clinical diagnosis at a rate of 35%. Among these patients, 21% were recommended a specific therapy. The investigators identified 31 new syndromes as a result of these efforts.

Methods

• Patients who were referred to the UDN over a period of 20 months were evaluated.
• Eligible patients included those who had an undiagnosed condition despite thorough evaluation by a health-care provider.
• The rate of diagnosis among patients who subsequently had a complete evaluation were assessed, and the effect of diagnosis on medical care was observed.

Results

• A total of 1,519 patients (53% female) were referred to the UDN, of whom 601 (40%) were accepted for evaluation.
• Of these patients, prior exome sequencing was performed on 192 (32%) patients.
• Among the applicants, symptoms were neurologic in 40%, musculoskeletal in 10%, immunologic in 7%, gastrointestinal in 7%, and rheumatologic in 6%.
• Of the 382 patients who had a complete evaluation, 132 received a diagnosis, yielding a diagnosis rate of 35%.
• Via clinical review alone, 15 diagnoses (11%) were made; via exome or genome sequencing, 98 (74%) diagnoses were made.
• Recommendations regarding changes in therapy were made in 21% of the diagnoses, changes in diagnostic testing was made in 37%, and variant-specific genetic counseling was suggested for 36%.
• Thirty-one new syndromes were defined.