BRIEF REPORTPierre Robin Syndrome and Wilms Tumor: An Unusual Association

Francesca Diomedi Camassei, MD,1 Alessandro Jenkner, MD,2

Enrico Bertini, MD,3 Cesare Bosman, MD,1 Alberto Donfrancesco , MD,2 andRenata Boldrini, MD1*

Key words: Wilms tumor; Pierre Robin complex; genetics; oncologic surveillance

The Pierre Robin syndrome or complex, characterizedby oral and mandibular defects, is a well-recognized mal-formation. It may occur as an isolated phenomenon or inassociation with a wide variety of syndromes and abnor-malities, many of which are genetically determined [1,2].The initiating defect may be a hypoplasia of the man-dibular area during the first weeks of gestation, withsubsequent failure of the tongue to descend, preventingfusion of the palatal shelves [2].

Wilms tumor is an embryonal neoplasm. In 7–10% ofcases it may be associated with malformations such asthe Beckwith-Wiedemann and WAGR syndromes [3,4],and in 2% of cases a familial occurrence has been dem-onstrated [5,6]. It may also be associated with less com-mon conditions, such as the Sotos, Perlman, Klippel-Trenaunay-Weber, Bloom, Poland, and linear sebaceousnevus syndromes as well as with trisomy 18 and Muli-brey nanism [4,6,7]. We report here for the first time thepairing of nephroblastoma with the Pierre Robin syndrome.

Our patient, a 4-month-old white girl when first seen,had been delivered at term after an uneventful pregnancy.There was no parental consanguinity, but family historywas positive for cleft lip/palate. Physical examination atadmission revealed a developmentally delayed infant(weight of 4.820 kg, <3rd percentile) with mild hypoto-nia, absent head control, and weak neuromuscular re-flexes. Facial anomalies included cleft soft palate, mi-crognathia, and glossoptosis. She had a palpablenontender right flank mass. Blood chemistry and urinaly-sis were within normal limits. Cytogenetic analysis of theperipheral blood revealed a normal female karyotype(46,XX). Abdominal ultrasound examination and CTscan showed a large solid mass arising within the rightkidney (8.5 × 6.2 × 5 cm), which was suggestive of amesoblastic nephroma. The left kidney was unremark-able and measured 4 × 3 × 1.5 cm. A CTscan of the chestruled out pulmonary metastases.

The patient underwent right nephroureterectomy andadrenal gland biopsy. During surgery a vascular abnor-mality, characterized by the right renal vein draining into

the right common iliac vein, was noted. Surgery waswell-tolerated. Histology revealed a stage I nephroblas-toma of the well-differentiated epithelial type, low riskaccording to the SIOP histopathologic classification, andno further treatment was given. On flow cytometry, neo-plastic cells displayed a diploid DNA content. At age 2years, the child successfully underwent surgical repair ofher cleft palate and 9 years after nephrectomy is alivewithout evidence of disease.

DISCUSSION

The association of nephroblastoma with the PierreRobin syndrome, here described, to our knowledge forthe first time, is likely to be fortuitous. It is neverthelessnoteworthy in that it may be part of a wider spectrum ofless common malformations and syndromes associatedwith this tumor [3,4,6,7]. The fact that Wilms tumor hasbeen identified as a component of various malformationsand overgrowth syndromes has recently provided a start-ing point for investigating the genetics of this neoplasm.Karyotype analyses have revealed constitutional dele-tions in two genes on chromosome 11 (namedWT1andWT2) and on chromosome 16q13-q22 that are involvedin Wilms tumor development [3]. Genetic linkage studiesin familial Wilms tumor kindreds have suggested thatother genes, yet to be identified with certainty, may pre-

1Department of Pathology, Ospedale Pediatrico Bambino Gesu` IR-CCS, Rome, Italy2Division of Pediatric Oncology, Ospedale Pediatrico Bambino Gesu`IRCCS, Rome, Italy3Division of Neurology, Ospedale Pediatrico Bambino Gesu` IRCCS,Rome, Italy

Contract grant sponsor: Ministero della Sanita`; Contract grant number:97/02/P/452 (to F.D.C.)

*Correspondence to: Dr. R. Boldrini, Servizio di Anatomia Patologica,Ospedale Pediatrico Bambino Gesu` IRCCS, Piazza S. Onofrio 4,00165 Rome, Italy. E-mail: boldrini@opbg.net

Received 27 October 1999; Accepted 12 January 2000

Medical and Pediatric Oncology 35:83–84 (2000)

© 2000 Wiley-Liss, Inc.

dispose to this tumor [5,6,8]. In particular, a geneticstudy in a large Canadian family has indicated linkage to17q12-q21 [6], but mapping of the familial Wilms tumorgene at this locus has not yet been performed. Althougha specific genetic mutation accounting for the PierreRobin syndrome has not yet been identified, interstitialdeletions of chromosome 17q have been reported to beassociated with craniofacial abnormalities, includingcleft palate [9,10]. Interestingly, other syndromes thathave been reported in association with Wilms tumor(breast-ovarian cancer syndrome and–tenuously–type 1neurofibromatosis) also map to chromosome 17q [6].

Future epidemiologic and genetic research should ad-dress these issues, in order to identify patients at in-creased risk of tumor development, at the same timecontributing to a better understanding of Wilms tumorbiology.

ADDENDUM

Since the manuscript was submitted for publication, atwo-year-old boy with a huge right nephroblastoma wasadmitted to our hospital. He had had surgery at age sevenmonths for cleft palate and the Pierre Robin syndrome.Cytogenetic analysis at that time had revealed a normalkaryotype.

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