title: Noonan syndrome-like disorder with loose anagen hair: a second case with neuroblastoma.
abstract: Noonan-like syndrome with loose anagen hair (NSLH), also known as Mazzanti syndrome, is a RASopathy characterized by craniofacial features resembling Noonan syndrome, cardiac defects, cognitive deficits and behavioral issues, reduced growth generally associated with GH deficit, darkly pigmented skin, and an unique combination of ectodermal anomalies. Virtually all cases of NSLH are caused by an invariant and functionally unique mutation in SHOC2 (c.4A>G, p.Ser2Gly). Here, we report on a child with molecularly confirmed NSLH who developed a neuroblastoma, first suspected at the age 3 months by abdominal ultrasound examination. Based on this finding, scanning of the SHOC2 coding sequence encompassing the c.4A>G change was performed on selected pediatric cohorts of malignancies documented to occur in RASopathies (i.e., neuroblastoma, brain tumors, rhabdomyosarcoma, acute lymphoblastic, and myeloid leukemia), but failed to identify a functionally relevant cancer-associated variant. While these results do not support a major role of somatic SHOC2 mutations in these pediatric cancers, this second instance of neuroblastoma in NSLAH suggests a possible predisposition to this malignancy in subjects heterozygous for the c.4A>G SHOC2 mutation.
authors.affiliation: Clinical Genetics Unit, Department of Obstetrics and Pediatrics, IRCCS S. Maria Nuova Hospital, Reggio Emilia, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Garavelli
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Cordeddu
authors.affiliation: Clinical Genetics Unit, Department of Obstetrics and Pediatrics, IRCCS S. Maria Nuova Hospital, Reggio Emilia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Errico
authors.affiliation: Department of Pediatric Oncology, Parma University Hospital, Parma, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bertolini
authors.affiliation: Department of Pediatrics, IRCCS S. Maria Nuova Hospital, Reggio Emilia, Italy.
authors.forename: Maria Elisabeth
authors.initials: ME
authors.lastname: Street
authors.affiliation: Clinical Genetics Unit, Department of Obstetrics and Pediatrics, IRCCS S. Maria Nuova Hospital, Reggio Emilia, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Rosato
authors.affiliation: Clinical Genetics Unit, Department of Obstetrics and Pediatrics, IRCCS S. Maria Nuova Hospital, Reggio Emilia, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Pollazzon
authors.affiliation: Clinical Genetics Unit, Department of Obstetrics and Pediatrics, IRCCS S. Maria Nuova Hospital, Reggio Emilia, Italy.|Department of Medical Genetics, Policlinico Sant'Orsola-Malpighi, University of Bologna, Italy.
authors.forename: Anita
authors.initials: A
authors.lastname: Wischmeijer
authors.affiliation: Clinical Genetics Unit, Department of Obstetrics and Pediatrics, IRCCS S. Maria Nuova Hospital, Reggio Emilia, Italy.
authors.forename: Ivan
authors.initials: I
authors.lastname: Ivanovski
authors.affiliation: IRCCS-Casa Sollievo della Sofferenza Hospital, Mendel Institute, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Daniele
authors.affiliation: Department of Pediatrics Radiology, Parma University Hospital, Parma, Italy.
authors.forename: Ermanno
authors.initials: E
authors.lastname: Bacchini
authors.affiliation: Department of Pediatrics Radiology, Parma University Hospital, Parma, Italy.
authors.forename: Alfonsa Anna
authors.initials: AA
authors.lastname: Lombardi
authors.affiliation: Department of Pediatric Oncology, Parma University Hospital, Parma, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Izzi
authors.affiliation: Department of Pediatrics, "Guglielmo da Saliceto" Hospital, Piacenza, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Biasucci
authors.affiliation: Department of Pediatric Surgery, Parma University Hospital, Parma, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Del Rossi
authors.affiliation: Deparment of Pathology, Parma University Hospital, Parma, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Corradi
authors.affiliation: Clinica Pediatrica, Università di Milano-Bicocca, Ospedale San Gerardo/Fondazione MBBM, Monza, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cazzaniga
authors.affiliation: Department of Pediatrics, Università "La Sapienza", Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Dominici
authors.affiliation: Department of Medical Genetics, Policlinico Sant'Orsola-Malpighi, University of Bologna, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Rossi
authors.affiliation: IRCCS-Casa Sollievo della Sofferenza Hospital, Mendel Institute, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Luca
authors.affiliation: Department of Pediatrics, Parma University Hospital, Parma, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernasconi
authors.affiliation: Department of Pediatrics, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Riccardi
authors.affiliation: Department of Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Legius
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Tartaglia
mesh_terms: D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009447:Neuroblastoma / Q000150:complications*; D009634:Noonan Syndrome / Q000150:complications / Q000503:physiopathology*
keywords: RASopathies; SHOC2; acute leukemias; brain tumors; cancer predisposition; mazzanti syndrome; neuroblastoma; noonan-like syndrome with loose anagen hair; rhabdomyosarcoma