Evaluation of remote phenotyping in individuals with 3q29 deletion syndrome and development of a transdiagnostic screening protocol that can be deployed remotely

Advances in genomics have resulted in a rapid expansion of the number of known rare genetic disorders (RGDs). However, the low frequency of RGDs presents a challenge for accurately describing the phenotypic spectrum of a given disorder. Remote phenotyping strategies are uniquely poised to address this knowledge gap. Here, we have piloted remote evaluation of cognitive ability and psychosis spectrum symptoms in 21 individuals with 3q29 deletion syndrome (3q29del) (57% male, mean age=14.3{+/-}8.6 years), a hallmark RGD. We find that remote cognitive assessment using the Penn Computerized Neurocognitive Battery and the Peabody Picture Vocabulary Test accurately captured full scale (r=0.710, p=0.001) and verbal IQ (r=0.637, p=0.003), respectively, as compared to in-person assessment with gold-standard instruments. Psychosis spectrum symptoms measured using the Structured Interview for Prodromal Syndromes were significantly correlated between in-person and remote evaluations (total score r=0.753, p=0.003; positive domain score r=0.806, p=0.0009). Based on the successful pilot of remote phenotyping in 3q29del, we designed a protocol for remote phenotyping of individuals with 3q29del. The phenotyping battery is comprised of caregiver-report and direct assessments to capture the spectrum of neurodevelopmental, neuropsychiatric, and medical features associated with the 3q29 deletion. While we designed the battery based on specific areas of concern for 3q29del, the high degree of phenotypic overlap between 3q29del and other RGDs renders this protocol amenable for implementation across a variety of RGDs, facilitating deeper understanding of the phenotypic spectrum and cross-disorder comparison. Ultimately, we hope that the increased utilization of remote phenotyping strategies will help to expand our understanding of RGDs at large, which will lead to improved clinical management strategies and better long-term outcomes for affected individuals and their families.