Our Cornelia de Lange Syndrome panel includes next generation sequencing (NGS) and deletion/duplication analysis of the NIPBL, SMC1A, HDAC8, RAD21, and SMC3 genes. Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using standardized methodology and quantified. Sequence enrichment of the targeted coding exons and adjacent intronic nucleotides is carried out by a bait-capture methodology using long biotinylated oligonucleotide probes, and is followed by polymerase chain reaction (PCR) and Next-Generation sequencing. Additional Sanger sequencing is performed for any regions missing or with insufficient read depth coverage for reliable heterozygous variant detection. Potentially homozygous variants, variants in regions complicated by pseudogene interference, and variant calls not satisfying depth of coverage and variant allele frequency quality thresholds are verified by Sanger sequencing. Gross deletion/duplication analysis for all genes is performed using a custom pipeline based on read-depth from NGS data and/or targeted chromosomal microarray with confirmatory MLPA when applicable.