CLEVELAND CLINIC PEDIATRIC CLINICAL CRITERIA FOR PTEN TESTING

The Cleveland Clinic pediatric clinical criteria is a systematic criteria based on evaluation of a large series of pediatric individuals with PTEN mutations.¹ These include patients who have been diagnosed with Cowden syndrome or Bannayan-Riley-Ruvalcaba Syndrome (BRRS). The criteria is applicable to patients without a family history of PTEN mutations. Individuals who have family members affected with PTEN mutations should be evaluated by specialist medical/genetics professionals.

CRITERIA

1. Macrocephaly ( ≥ 2 standard deviations from normal)
2. At least one of the following four additional criteria should be present:
   • Autism or developmental delay
   • Dermatologic features, including lipomas, trichilemmomas, oral papillomas, or penile freckling
   • Vascular features, such as arteriovenous malformations, or hemangiomas
   • Gastrointestinal polyps

Other clinical diagnoses that should lead to evaluation for the above clinical features include pediatric onset thyroid cancer and pediatric onset germ cell tumors.

The Cleveland Clinic criteria for adult and pediatric subjects has been demonstrated to be superior in performance to the current NCCN clinical criteria (2010) in selection of patients for PTEN mutation screening. This evaluation was reported in the only prospective study conducted in 3,024 probands recruited over 10 years.¹

¹ Tan MH, Mester M, Peterson C, Yang Y, Chen JL, Rybicki LA, Milas K, Pederson H, Remzi B, Orloff MS, Eng C (2011). A Clinical Scoring System for Selection of Patients for PTEN Mutation Testing is Proposed on the Basis of a Prospective Study of 3,042 Probands. Am J Hum Genet. (in press)