Feingold syndrome (FS) is a syndromic microcephaly entity for which MYCN is the major disease-causing gene. We studied the expression pattern of MYCN at different stages of human embryonic development and collected a series of 17 FS and 12 isolated oesophageal atresia (IOA) cases. An MYCN gene deletion/mutation was identified in 47% of FS cases exclusively. We hypothesized that mutations or deletions of highly conserved non-coding elements (HCNEs) at the MYCN locus could lead to its misregulation and thereby to FS and/or IOA. We subsequently sequenced five HCNEs at the MYCN locus and designed a high-density tiling path comparative genomic hybridization array of 3.3 Mb at the MYCN locus. We found no mutations or deletions in this region, supporting the hypothesis of genetic heterogeneity in FS. 3,4 Conversely, MYCN amplification is a prognostic factor for a bad outcome and is found in about 10% of neuroblastomas. 5 In this study, we studied the expression pattern of MYCN at different stages of human embryonic development, and screened a cohort of 17 patients suspected of FS and 12 patients with isolated oesophageal atresia (IOA). We identified a heterozygous mutation/ deletion in seven FS cases (47%) and no mutation or deletion in IOA. Some highly conserved non-coding elements (HCNEs), able to direct N-myc expression, have been identified in transgenic mice [6][7][8] We hypothesized that deregulation of tissue-or stage-specific MYCN expression following mutation or disruption of regulatory HCNEs at the MYCN locus could lead to FS and/or IOA. We subsequently sequenced five HCNEs at the MYCN locus and searched for small deletions in the 3.3-Mb vicinity of MYCN.