Overview

Over 50% of pediatric neurological and neurodevelopmental disorders lack a molecular diagnosis after standard DNA sequencing and molecular karyotyping. This is due to technical limitations, incomplete variant interpretation, and inadequate genotype-phenotype correlations. New sequencing technologies are crucial for clinical decision-making, offering complete profiles of variants in a patient's DNA to personalize treatment. Optical Genome Mapping (OGM) can detect nearly all structural variants in one experiment. This project aims to use OGM alongside NGS to improve diagnostic yield in 60 children with severe disorders who tested negative for NGS/CMA.

Eligibility

Inclusion Criteria:

• individuals without a molecular diagnosis (negative to ES/CMA analyses);
• individuals with genetic diagnoses that explain only one component of their primary phenotype;
• individuals carrying one or more variants of uncertain clinical significance
• individuals with a phenotype highly reminiscent of clinically and molecularly well-defined syndromes (i.e., Marfan Syndrome) but negative to routine molecular analysis.

Exclusion Criteria:

• individuals who have not undergone initial diagnostic genetic tests (ES/CMA)