Pediatric rare diseases, typically resulting from genetic variations,
1 can emerge from before birth to childhood, posing notable clinical challenges. First, diagnosing rare diseases and other genetic conditions can be daunting due to vague or poorly defined clinical symptoms or lack of knowledge around many disorders as well as around the extension and functional impact of genetic variations.
2 Conventional diagnostic tests typically involve sequential single-gene analysis,
3 while for many heterogeneous clinical conditions, multigene panels or genome-wide sequencing methods are necessary to identify the causative variations.
4 Various factors greatly complicate diagnosing rare diseases in the pediatric population, such as the considerable number of disease-associated genes, the absence of pathognomonic features or signs, and the heterogeneous nature of the underlying pathogenic changes.
5 The process is often lengthy, requires prompt recognition of suggestive features and timely referral to different specialists,
6 and may require multiple attempts.