Five additional Costello syndrome patients with rhabdomyosarcoma: proposal for a tumor screening protocol

Am J Med Genet. 2002 Feb 15;108(1):80-7. doi: 10.1002/ajmg.10241.


We report five new cases of rhabdomyosarcoma (RMS) in Costello syndrome. These cases, combined with those previously reported, increase the number of solid tumors to 17 (10 RMSs, 3 neuroblastomas, 2 bladder carcinomas, 1 vestibular schwannoma, 1 epithelioma), in at least 100 known Costello syndrome patients. Despite possible ascertainment bias, and the incomplete identification of all Costello syndrome patients, the tumor frequency could be as high as 17%. This is comparable to the 7-21% frequency of solid tumors in Beckwith-Wiedemann syndrome (BWS), and may justify tumor screening. Based on the recommendations for screening BWS patients, we propose a screening protocol consisting of ultrasound examination of the abdomen and pelvis every 3-6 months until age 8-10 years for RMS and abdominal neuroblastoma; urine catecholamine metabolite analysis every 6-12 months until age 5 years for neuroblastoma; and urinalysis for hematuria annually for bladder carcinoma after age 10 years. These recommendations may need to be modified, as new information becomes available. Potential criticism of the tumor screening protocol concerns the lack of evidence for improved outcome, and possible overestimation of the tumor risk. The ability of RMSs to occur at various sites complicates tumor screening, but 8 of the 10 RMSs in Costello syndrome patients originated from the abdomen, pelvis and urogenital area. Prior diagnosis of Costello syndrome is a prerequisite for the implementation of any screening protocol. The diagnosis of Costello syndrome should also be considered in individuals with RMS and physical findings suggestive of Costello syndrome.

MeSH terms

  • Abnormalities, Multiple* / diagnostic imaging
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Clinical Protocols
  • Failure to Thrive / genetics
  • Failure to Thrive / pathology
  • Female
  • Humans
  • Infant
  • Intestinal Neoplasms / diagnosis
  • Intestinal Neoplasms / genetics
  • Joint Instability / genetics
  • Joint Instability / pathology
  • Male
  • Mass Screening
  • Polyhydramnios / pathology
  • Pregnancy
  • Rhabdomyosarcoma* / diagnosis
  • Rhabdomyosarcoma* / diagnostic imaging
  • Rhabdomyosarcoma* / genetics
  • Rhabdomyosarcoma* / pathology
  • Syndrome
  • Ultrasonography