title: Suprasellar mass mimicking a hypothalamic glioma in a patient with a complete PROP1 deletion.
abstract: Mutations in PROP1 are the most frequent defect detected in patients with combined pituitary hormone deficiency (MIM #262600), characterized by a clinical phenotype of proportionate growth deficit due to impaired production of growth hormone in combination with deficiency of one or more of the additional anterior pituitary hormones. Approximately one third of patients with PROP1 inactivating mutations present with abnormal development of the anterior lobe of the pituitary gland as revealed by MRI. We report on the clinical and molecular characterization of the fourth complete PROP1 deletion in a girl with proportional short stature, combined pituitary hormone deficiency and a suprasellar mass mimicking a hypothalamic glioma. The proband, born to consanguineous parents, presented with proportional growth failure (height 108.8 cm, -3.48 SDS), combined pituitary hormone deficiency (GH, TSH, PRL and gonadotropins) and a suprasellar mass with optic chiasm invasion, compatible with a diagnosis of chiasmatic hypothalamic glioma, as revealed by MRI. PROP1 mutation screening by PCR and MLPA detected a homozygous deletion of the entire PROP1. The deletion was delimited to at least 7.7 kb upstream of PROP1 and more finely to ∼541-74 bp downstream from PROP1 by aCGH and PCR mapping. We describe the fourth case with a complete PROP1 deletion in homozygosis. The apparent location of the respective 5' (within a highly repetitive region, rich in Alu sequences) and 3' (within an Alu sequence) breakpoints, suggests that the deletion may have arisen through homologous recombination. The differentiation between PROP1 mutation associated pituitary enlargements from craniopharyngioma, pituitary adenoma, dys-germinoma, or Rathke's pouch cyst, is critical for the correct patient management. It is important to recognize that PROP1 mutations can present associated with evolving pituitary masses and/or other MRI alterations of the pituitary during early childhood and that surgery is not indicated in these patients. Therefore, in the presence of combined pituitary hormone deficiency and a pituitary or hypothalamic mass, PROP1 analysis should be considered before referring the patient to a neurosurgeon.
authors.affiliation: Department of Pediatric Hematology, Kanuni Sultan Suleyman Education and Research Hospital, Istanbul, Turkey.
authors.forename: Arzu
authors.initials: A
authors.lastname: Akcay
authors.forename: Korkut
authors.initials: K
authors.lastname: Ulucan
authors.forename: Necati
authors.initials: N
authors.lastname: Taskin
authors.forename: Mehmet
authors.initials: M
authors.lastname: Boyraz
authors.forename: Teoman
authors.initials: T
authors.lastname: Akcay
authors.forename: Olga
authors.initials: O
authors.lastname: Zurita
authors.forename: Ana
authors.initials: A
authors.lastname: Gomez
authors.forename: Karen E
authors.initials: KE
authors.lastname: Heath
authors.forename: Angel
authors.initials: A
authors.lastname: Campos-Barros
mesh_terms: D002895:Chromosomes, Human, Pair 5; D055028:Comparative Genomic Hybridization; D003937:Diagnosis, Differential; D005260:Female; D023061:Gene Order; D005910:Glioma / Q000175:diagnosis*; D018398:Homeodomain Proteins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007029:Hypothalamic Neoplasms / Q000175:diagnosis*; D007223:Infant; D008279:Magnetic Resonance Imaging; D010375:Pedigree; D010902:Pituitary Gland / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D011859:Radiography; D017384:Sequence Deletion
chemical_list: D018398:Homeodomain Proteins; C102134:Prophet of Pit-1 protein
keywords: CPHD; Combined pituitary hormone deficiency; Hypothalamic glioma; MRI; PROP1 deletion; Pituitary mass; Suprasellar mass; combined pituitary hormone deficiency; magnetic resonance imaging