Tenorio syndrome: Description of 14 novel cases and review of the clinical and molecular features.

Stasia Hadjiyannakis, Pablo Lapunzina, Feliciano J Ramos, Camerun Washington, Elliot S Stolerman, Sara Álvarez, María Del Mar O'Callaghan Cord, Antonio Federico Martínez-Monseny, Lucile Pinson, Fernando Santos-Simarro, Frederic Tran-Mau-Them, James Lespinasse, Jair Antonio Tenorio-Castaño, Chantal Morel, Kameryn M Butler, Sergio Ramos, Natalia Gallego, Laurence Faivre, Allan Bayat, Gloria Bueno-Lozano, Guillermo Lay-Son, Alberto Fernández-Jaén, Pedro Arias

Journal: Clinical genetics 2022;100(4):405-411

PMID: 34196401

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Abstract

Tenorio syndrome (TNORS) (OMIM #616260) is a relatively recent disorder with very few cases described so far. Clinical features included macrocephaly, intellectual disability, hypotonia, enlarged ventricles and autoimmune diseases. Molecular underlying mechanism demonstrated missense variants and a large deletion encompassing RNF125, a gene that encodes for an U3 ubiquitin ligase protein. Since the initial description of the disorder in six patients from four families, several new patients were diagnosed, adding more evidence to the clinical spectrum. In this article, we described 14 additional cases with deep phenotyping and make an overall review of all the cases with pathogenic variants in RNF125. Not all patients presented with overgrowth, but instead, most patients showed a common pattern of neurodevelopmental disease, macrocephaly and/or large forehead. Segregation analysis showed that, though the variant was inherited in some patients from an apparently asymptomatic parent, deep phenotyping suggested a mild form of the disease in some of them. The mechanism underlying the development of this disease is not well understood yet and the report of further cases will help to a better understanding and clinical characterization of the syndrome.

Address: CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.; Overgrowth Syndromes Laboratory, INGEMM, Instituto de Genética Médica y Molecular, IdiPAZ, Hospital Universitario la Paz, Universidad Autónoma de Madrid (UAM), Madrid, Spain.; Ithaca, European Reference Network, Brussels, Belgium.; Hospital Universitario Quirónsalud Madrid, Universidad Europea de Madrid, Spain.; Unidad de Genética, División de Pediatría, Facultad de Medicina, Pontificia Universidad Católica de, Chile.; Unit of Clinical Genetics, Service of Paediatrics, School of Medicine, University Hospital 'Lozano Blesa, University of Zaragoza, CIBERER-GCV02 and ISS-Aragón, Zaragoza, Spain.; Department of Pediatrics, Hvidovre Hospital, University of Copenhagen, Denmark.; Centre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD, Hôpital d'Enfants, CHU Dijon, Dijon, France.; UMR1231 GAD, Inserm - Université Bourgogne-Franche Comté, Dijon, France.; Cytogenetics Laboratory, Greenwood Genetic Center, Greenwood, South Carolina, USA.; University Health Network, Fred A. Litwin Family Centre in Genetic Medicine, Toronto, Ontario, Canada.; Department of Medicine, University of Toronto, Toronto, Ontario, Canada.; Division of Endocrinology and Metabolism, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada.; Service de Cytogenetique, Centre Hospitalier de Chambéry, Chambéry, France.; UF6254 Innovation en Diagnostic Genomique des Maladies Rares Bat, Pôle de Biologie, CHU, Dijon, France.; Clinical Genetics section, INGEMM, Instituto de Genética Médica y Molecular, IdiPAZ, Hospital Universitario la Paz, Universidad Autónoma de Madrid (UAM), Madrid, Spain.; Départment de Génétique Médicale, Maladies Rares et Médecine Personnalisée, CHU de Montpellier, Montpellier, France.; Clinical Genetics section, Department of Genetic and Molecular Medicine and Pediatric Institute of Rare Diseases (IPER), Hospital Sant Joan de Déu, Barcelona, Spain.; Department of Pediatric Neurology, Hospital Sant Joan de Déu, Barcelona, Spain.; NIMGENETICS, Calle de Anabel Segura, Madrid, Spain.; Unit of Pediatric Endocrinology, Service of Paediatrics, University Hospital Lozano Blesa, Zaragoza, Spain.

DOI: 10.1111/cge.14020

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MeSH Terms: Abnormalities, Multiple, Alleles, Amino Acid Substitution, Databases, Genetic, Facies, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation, Genotype, Humans, Phenotype, Syndrome, Ubiquitin-Protein Ligases, Exome Sequencing