Letter to the Editor

Wolf-Hirschhorn Syndrome andPitt-Rogers-Danks Syndrome

To the Editor:

At the 46th Annual Meeting of the American Societyof Human Genetics in San Francisco, we presented apaper on the natural history of Wolf-Hirschhorn syn-drome (WHS). We reported on our experience witholder patients with WHS [Battaglia et al., 1996], andwe reviewed the previous literature on that issue andon a similar disorder, the so-called Pitt-Rogers-Dankssyndrome (PRDS) [Pitt et al., 1984; Donnai, 1986; Oor-thuys and Bleeker-Wagemakers, 1989; Lizcano-Gil etal., 1995].

We must say that the more carefully we perused thecase histories and pictures of patients with PRDS, themore we became convinced that the ‘‘Pitt-Rogers-Danks syndrome’’ cases were just patients with 4p de-letion who had been missed. In addition, the describedcases had received either no chromosomal studies(1 case) or only standard cytogenetics (regular G-banding, 5 cases; high-resolution banding, 1 case).None of the cases had received fluorescence in situ hy-bridization (FISH) studies.

As we reported at the above-mentioned meeting, it isclear that whenever dealing with patients showingclinical signs suggestive of WHS, it is highly recom-mended to carry out high-resolution banding and FISHanalyses, in order not to miss the diagnosis. Since thereis little information on older patients with WHS, it iseasy to misdiagnose them.

Now we understand that 2 of the original patientspublished as PRDS [Pitt et al., 1984] did eventuallyreceive a FISH analysis for WHS, showing a 4p micro-deletion [Clemens et al., 1996]. In addition, there havebeen two brief reports [Donnai, 1996; Lindeman-Kusseet al., 1996] dealing with PRDS and 4p deletion. Again,the more carefully we read them, the more we becomeconvinced that such cases are WHS. Differences be-tween the two syndromes are negligible, while similari-ties are compelling. We think it is specious to arguethat just a flat glabella or a wide mouth may be suffi-cient to retain the existence of a distinct entity, previ-

ously identified only on the basis of negative standardcytogenetic studies. In addition, Clemens et al. [1996]noted that their patient 2, ‘‘previously diagnosed withPRDS, is developing a Greek warrior helmet facial ap-pearance consistent with WHS.’’

We conclude that PRDS is not a separate clinicalentity. The PRDS cases represent the milder end of theWHS spectrum, with most of the older ones misdiag-nosed most likely because the WHS pictures from theliterature are mostly of infants or young children. Thishas made it difficult to obtain a sense of the phenotypeof older cases of WHS.

Indeed, we agree with Donnai [1996] that all remain-ing cases labelled as PRDS should be studied with mo-lecular techniques.

REFERENCESBattaglia A, Carey JC, Cederholm P, Viskochil D, Brothman A (1996):

Natural history experience with 11 cases of Wolf-Hirschhorn syn-drome. Am J Hum Genet 59:36.

Clemens M, Martsolf JT, Rogers JG, Mowery-Rushton P, Surti U, Mc-Pherson E (1996): Pitt-Rogers-Danks syndrome: The result of a 4pmicrodeletion. Am J Med Genet 66:95–100.

Donnai D (1986): A further patient with the Pitt-Rogers-Danks syndromeof mental retardation, unusual face, and intrauterine growth retarda-tion. Am J Med Genet 24:29–32.

Donnai D (1996): Editorial comment: Pitt-Rogers-Danks syndrome andWolf-Hirschhorn syndrome. Am J Med Genet 66:101–103.

Lindeman-Kusse MC, Van Haeringen A, Hoorweg-Nijman JJG, BrunnerRG (1996): Cytogenetic abnormalities in two new patients with Pitt-Rogers-Danks phenotype. Am J Med Genet 66:104–112.

Lizcano-Gil LA, Garcia-Cruz D, Garcia-Cruz O, Sanchez-Corona J (1995):Pitt-Rogers-Danks syndrome: Further delineation. Am J Med Genet55:420–422.

Oorthuys JWE, Bleeker-Wagemakers EM (1989): A girl with the Pitt-Rogers-Danks syndrome. Am J Med Genet 32:140–141.

Pitt DB, Rogers JG, Danks DM (1984): Mental retardation, unusual face,and intrauterine growth retardation: A new recessive syndrome? Am JMed Genet 19:307–313.

Agatino Battaglia*Institute for Clinical Research Stella Maris-Institute

of Child Neurology and PsychiatryUniversity of PisaCalambrone (Pisa), Italy

John C. CareyDivision of Medical GeneticsDepartment of PediatricsUniversity of Utah, HSCSalt Lake City, Utah

*Correspondence to: Agatino Battaglia, Institute for ClinicalResearch Stella Maris-Institute of Child Neurology and Psychia-try, University of Pisa, via dei Giacinti 2, 56018 Calambrone(Pisa), Italy.

Received 27 August 1997; Accepted 3 September 1997

American Journal of Medical Genetics 75:541 (1998)

© 1998 Wiley-Liss, Inc.