Our analysis revealed unbiased tissue-specific long-range interactions, and some of those interactions overlapped with disease-associated deletions and active regulatory elements, such as the NR2F1 locus, which is involved in Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS), and the DLX5/6 locus, which is linked to Split-Hand/Foot Malformation Type 1 (SHFM1), suggesting that structural variants disrupting local chromatin architecture cause transcriptional dysregulation. Here, DLX5 is linked to Bosch-Boonstra-Schaaf optic atrophy syndrome.