Wolf–Hirschhorn syndrome (WHS), also known as chromosome deletion Dillan 4p syndrome, Pitt-Rogers-Danks syndrome (PRDS) or Pitt syndrome, was first described in 1961 by Americans Herbert L. Cooper and Kurt Hirschhorn and, thereafter, gained worldwide attention by publications by the German Ulrich Wolf, and Hirschhorn and their co-workers, specifically their articles in the German scientific magazine Humangenetik. It is a characteristic phenotype resulting from a partial deletion of chromosomal material of the short arm of chromosome 4 (del(4p16.3)).
Deletion of short arm of the chromosome 784 in a patient with Wolf-Hirschhorn syndrome
Wolf–Hirschhorn syndrome is caused by a partial deletion of the short arm of chromosome 4, particularly in the region of WHSC1 and WHSC2. About 87% of cases represent a de novo deletion, while about 13% are inherited from a parent with a chromosome translocation. In the cases of familial translocation, there is a 2 to 1 excess of maternal transmission. Of the de novo cases, 80% are paternally derived. Severity of symptoms and expressed phenotype differ based on the amount of genetic material deleted. The critical region for determining the phenotype is at 4p16.3 and can often be detected through genetic testing and fluorescence in situ hybridization (FISH). Genetic testing and genetic counseling is offered to affected families.