EPID-18. NOONAN SYNDROME CAN BE ASSOCIATED WITH HIGH GRADE GLIOMA; A REPORT OF TWO CASES. (6th November 2017)

• Record Type: Journal Article
• Authors: El-Ayadi, Moatasem; Ansari, Marc; Kühnöl, Caspar; Bendel, Anne; Sturm, Dominik; Pietsch, Torsten; Kramm, Christof; von Bueren, André
• Is Part Of: Neuro-oncology. Volume 21(2019)Supplement 6
• Page Start: vi72
• Page End: vi72
• Publication Date: 2017-11-06
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/nox168.295
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Noonan syndrome (NS), an autosomal dominant disorder, is characterized by short stature, congenital heart defects, developmental delay, and facial dysmorphism. PTPN11 germline mutations are the most common cause of NS. Patients with NS are at an increased risk of developing hematologic malignancies and solid tumors, including brain tumors. Commonly associated brain tumors are dysembryoplastic neuroepithelial tumor (DNET) and low-grade astrocytoma. Here we report two cases of anaplastic astrocytoma (AA) with PTPN11 -related NS. These are, to the best of our knowledge, the only two high grade glioma (HGG) cases with NS reported in the literature. The first case is a 14-year-old girl presenting with headaches, head tilt, and ataxia. MRI demonstrated a heterogeneously enhancing mass arising from the left brainstem/cerebellar peduncle. The tumor was near completely resected and pathology was consistent with a HGG. Due to short stature and mild dysmorphism, she underwent PTPN11 mutational germline analysis revealing a heterozygous c.922 A>G (p.Asn308Asp) PTPN11 mutation consistent with NS. The second case is a 9-year-old male presenting with a history of repeated vomiting and headaches. MRI showed multifocal disease involving the 3 rd ventricle, cerebellum and fornix, thus only subtotal surgical resection was feasible and pathology revealed AA. Molecular analysis indicated amplification of CDK4 and MDM2 with loss of CDKN2A/B as well as an FGFR1 hotspot mutation. The DNA methylation profile was consistent with anaplastic pilocytic astrocytoma. The patient had dysmorphic features with hypertelorism and mental retardation. Mutational germline analysis showed PTPN11 heterozygous mutation c.5C>T (p.Thr2IIe). Both cases were centrally reviewed (T.P.) and neuropathological diagnosis of anaplastic astrocytoma, IDH wild-type was confirmed. Systematic review of literature identified 24 cases of brain tumors associates with NS, all of which were low-grade glial or glioneuronal tumors except for one case of medulloblastoma. Our report points out possible association of NS with HGG.