title: Premature Epiphyseal Closure of the Lower Extremities Contributing to Short Stature after cis-Retinoic Acid Therapy in Medulloblastoma: A Case Report.
abstract: BACKGROUND
  Prolonged cis-retinoic acid (RA) exposure contributes to premature epiphyseal closure. cis-RA is administered in various treatment regimens for pediatric cancers, thus increasing the risk for bone deformities and compromised growth.
  
  
  RESULTS
  We present a case of premature epiphyseal closure in a 9-year-old female with a history of medulloblastoma and treatment with a multimodal regimen including cis-RA. She was subsequently diagnosed with radiation-induced endocrine late effects including hypothyroidism and growth hormone deficiency (GHD). Seven months after initiation of GH therapy, an increased prominence of the wrists and knees combined with a deceleration in growth velocity prompted further evaluation; radiographs revealed bilateral premature closure of the distal femur and proximal tibia growth plates despite normal left wrist bone age.
  
  
  CONCLUSIONS
  High doses of vitamin A and its analogs are linked to premature closure of the lower-extremity growth plates in animals and children. Pediatric brain tumor patients are at increased risk of growth failure due to concurrent radiation-induced GHD, damage to the spinal bones, and cis-RA-associated premature closure of the lower-extremity growth plates, with significant reduction in adult stature. A better appreciation of the detrimental effect of cis-RA on the growing skeleton is needed to monitor at-risk patients and to provide timely interventions.
authors.affiliation: Department of Pediatrics, Division of Oncology, The Children's Hospital of Philadelphia, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa., USA.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Noyes
authors.forename: Michael A
authors.initials: MA
authors.lastname: Levine
authors.forename: Jean B
authors.initials: JB
authors.lastname: Belasco
authors.forename: Sogol
authors.initials: S
authors.lastname: Mostoufi-Moab
mesh_terms: D000328:Adult; D001847:Bone Diseases / Q000139:chemically induced / Q000473:pathology; D002648:Child; D005260:Female; D006130:Growth Disorders / Q000139:chemically induced / Q000473:pathology; D006132:Growth Plate / Q000473:pathology*; D019382:Human Growth Hormone / Q000172:deficiency; D006801:Humans; D035002:Lower Extremity; D008527:Medulloblastoma / Q000188:drug therapy* / Q000473:pathology; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D019382:Human Growth Hormone; D014212:Tretinoin