| Autor: |
Carcavilla A; Pediatric Endocrinology Department, Hospital Universitario La Paz, 28046 Madrid, Spain.; Multidisciplinary Unit for RASopathies, Hospital Universitario La Paz, 28046 Madrid, Spain., Cambra A; Molecular Diagnostics Laboratory, Department of Laboratory Medicine, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain.; Gregorio Marañon Health Research Institute (IiSGM), 28009 Madrid, Spain., Santomé JL; Molecular Diagnostics Laboratory, Department of Laboratory Medicine, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain.; Gregorio Marañon Health Research Institute (IiSGM), 28009 Madrid, Spain., Seidel V; Clinical Genetics Unit, Pediatrics Department, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain., Cruz J; Pediatrics Department, Hospital Universitario Doce de Octubre, 28041 Madrid, Spain., Alonso M; Pediatrics Department, Hospital Ramón y Cajal, 28034 Madrid, Spain., Pozo J; Pediatric Endocrinology Department, Hospital Universitario Niño Jesús, 28009 Madrid, Spain., Valenzuela I; Genetics Department, Hospital Universitario Vall D'Hebrón, 08035 Barcelona, Spain., Guillén-Navarro E; Genetics Department, Hospital Virgen de la Arrixaca, 30120 Murcia, Spain., Santos-Simarro F; Multidisciplinary Unit for RASopathies, Hospital Universitario La Paz, 28046 Madrid, Spain.; Institute of Medical & Molecular Genetics, Hospital Universitario la Paz, 28046 Madrid, Spain., González-Casado I; Pediatric Endocrinology Department, Hospital Universitario La Paz, 28046 Madrid, Spain.; Multidisciplinary Unit for RASopathies, Hospital Universitario La Paz, 28046 Madrid, Spain., Rodríguez A; Gregorio Marañon Health Research Institute (IiSGM), 28009 Madrid, Spain.; Pediatric Endocrinology, Pediatrics Department, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain., Medrano C; Gregorio Marañon Health Research Institute (IiSGM), 28009 Madrid, Spain.; Pediatric Cardiology Department, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain., López-Siguero JP; Pediatric Endocrinology Department, Hospital Regional Universitario de Málaga, 29010 Málaga, Spain., Ezquieta B; Molecular Diagnostics Laboratory, Department of Laboratory Medicine, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain.; Gregorio Marañon Health Research Institute (IiSGM), 28009 Madrid, Spain. |
| Abstrakt: |
Molecular study has become an invaluable tool in the field of RASopathies. Treatment with recombinant human growth hormone is approved in Noonan syndrome but not in the other RASopathies. The aim of this study was to learn about the molecular base of a large cohort of patients with RASopathies, with particular emphasis on patients with pathogenic variants in genes other than PTPN11 , and its potential impact on rGH treatment indication. We reviewed the clinical diagnosis and molecular findings in 451 patients with a genetically confirmed RASopathy. HRAS alterations were detected in only 2 out of 19 patients referred with a Costello syndrome suspicion, whereas pathogenic variants in RAF1 and SHOC2 were detected in 3 and 2, respectively. In 22 patients referred with a generic suspicion of RASopathy, including cardiofaciocutaneous syndrome, pathogenic alterations in classic Noonan syndrome genes ( PTPN11 , SOS1 , RAF1 , LZTR1, and RIT1 ) were found in 7 patients and pathogenic variants in genes associated with other RASopathies ( HRAS , SHOC2, and PPPCB1) in 4. The correct nosological classification of patients with RASopathies is critical to decide whether they are candidates for treatment with rhGH. Our data illustrate the complexity of differential diagnosis in RASopathies, as well as the importance of genetic testing to guide the diagnostic orientation in these patients. |
