PITT-ROGERS-DANKS-SYNDROME AND WOLF-HIRSCHHORN-SYNDROME ARE CAUSED BYA DELETION IN THE SAME REGION ON CHROMOSOME 4P16.3

Recently, a deletion of chromosome 4pter was found in three patients w ith Pitt-Rogers-Danks syndrome. We investigated two of these patients, by means of DNA and FISH studies, together with two additional patien ts with Pitt-Rogers-Danks syndrome, to determine the critical region o f the deletion in these patients and to compare this with the critical region in Wolf-Hirschhorn syndrome. All four patients showed terminal deletions of chromosome 4p of different sizes. One of them appeared t o have an unbalanced karyotype caused by a cryptic translocation t(4;8 ) in the mother, resulting in a deletion of chromosome 4pter and a dup lication of chromosome 8pter. The localisation of the Wolf-Hirschhorn critical region has been confined to approximately I Rib between D4S43 and D4S115. Our study shows that the deletions in four patients with the Pitt-Rogers-Danks syndrome overlap the Wolf-Hirschhorn critical re gion and extend beyond this in both directions. This study, combined w ith the fact that our third patient, who was previously described as a Pitt-Rogers-Danks patient, but who now more closely resembles a Wolf- Hirschhorn patient, makes it likely that Pitt-Rogers-Danks and Wolf-Hi rschhorn syndromes are different clinical phenotypes resulting from a deletion in the same microscopic region on chromosome 4p16.