One of the key discoveries of vertebrate genome sequencing projects has been the 
identification of highly conserved noncoding elements (CNEs). Some 
characteristics of CNEs include their high frequency in mammalian genomes, their 
potential regulatory role in gene expression, and their enrichment in gene 
deserts nearby master developmental genes. The abnormal development of neural 
crest cells (NCCs) leads to a broad spectrum of congenital malformation(s), 
termed neurocristopathies, and/or tumor predisposition. Here we review recent 
findings that disruptions of CNEs, within or at long distance from the coding 
sequences of key genes involved in NCC development, result in neurocristopathies 
via the alteration of tissue- or stage-specific long-distance regulation of gene 
expression. While most studies on human genetic disorders have focused on 
protein-coding sequences, these examples suggest that investigation of genomic 
alterations of CNEs will provide a broader understanding of the molecular 
etiology of both rare and common human congenital malformations.