Cytogenetic abnormalities in two new patients with Pitt-Rogers-Danks phenotype.

We describe 2 patients with a combination of findings strikingly similar to those described by Pitt et al. [1984], consisting of severe mental retardation, pre- and postnatal growth retardation, history of seizures, microcephaly, ocular proptosis, mid-face hypoplasia, short and flat philtrum, and wide mouth. Our cases included, a total of only 9 patients has been described. One of our patients was treated with growth hormone and responded with a marked increase in growth velocity and skeletal maturation. Chromosome analysis was performed; both patients have a deletion of 4p as is found in Wolf-Hirschhorn syndrome. A comparison is made between our patients and patients with the Wolf-Hirschhorn syndrome (4p-). We conclude that the Pitt-Rogers-Danks phenotype is associated with 4p- in our two patients and that the syndromic status of the Pitt-Rogers-Danks status should be reassessed.

Pitt-Rogers-Danks syndrome and Wolf-Hirschhorn syndrome are caused by a deletion in the same region on chromosome 4p 16.3.

Recently, a deletion of chromosome 4pter was found in three patients with Pitt-Rogers-Danks syndrome. We investigated two of these patients, by means of DNA and FISH studies, together with two additional patients with Pitt-Rogers-Danks syndrome, to determine the critical region of 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 to have an unbalanced karyotype caused by a cryptic translocation t(4;8) in the mother, resulting in a deletion of chromosome 4pter and a duplication of chromosome 8pter. The localisation of the Wolf-Hirschhorn critical region has been confined to approximately 1 Mb between D4S43 and D4S115. Our study shows that the deletions in four patients with the Pitt-Rogers-Danks syndrome overlap the Wolf-Hirschhorn critical region and extend beyond this in both directions. This study, combined with 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-Hirschhorn syndromes are different clinical phenotypes resulting from a deletion in the same microscopic region on chromosome 4p16.