Table 1 Inclusion and exclusion criteria.

Pediatric patient (0–18 years)

Investigated for more than two years since tertiary presentation

Likely monogenic disorder

Copy-number variant responsible for phenotype

Complex condition as defined by two or more of

Previous genetic sequencing (single-gene or multigene panel) or enrollment in other GS study

• multisystem disorder with three or more organ systems involved

Single-gene disorder unlikely

• severe condition with high morbidity and mortality

Novel syndrome, i.e., phenotype-driven candidate gene panel cannot be generated

• severe limitations on function and activities of daily living

Secure clinical diagnosis of a monogenic disorder, e.g., achondroplasia, CHARGE syndrome