What are the genetic changes related to Wolf-Hirschhorn syndrome ?
Wolf-Hirschhorn syndrome is caused by a deletion of genetic material near the end of the short (p) arm of chromosome 4. This chromosomal change is sometimes written as 4p-. The size of the deletion varies among affected individuals; studies suggest that larger deletions tend to result in more severe intellectual disability and physical abnormalities than smaller deletions.  The signs and symptoms of Wolf-Hirschhorn are related to the loss of multiple genes on the short arm of chromosome 4. WHSC1, LETM1, and MSX1 are the genes that are deleted in people with the typical signs and symptoms of this disorder. These genes play significant roles in early development, although many of their specific functions are unknown. Researchers believe that loss of the WHSC1 gene is associated with many of the characteristic features of Wolf-Hirschhorn syndrome, including the distinctive facial appearance and developmental delay. Deletion of the LETM1 gene appears to be associated with seizures or other abnormal electrical activity in the brain. A loss of the MSX1 gene may be responsible for the dental abnormalities and cleft lip and/or palate that are often seen with this condition.  Scientists are working to identify additional genes at the end of the short arm of chromosome 4 that contribute to the characteristic features of Wolf-Hirschhorn syndrome.