Tenorio syndrome: Description of 14 novel cases and review of the clinical and molecular features,Clinical Genetics

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Tenorio syndrome: Description of 14 novel cases and review of the clinical and molecular features
Clinical Genetics ( IF 2.9 ) Pub Date : 2021-07-01 , DOI: 10.1111/cge.14020
Jair Antonio Tenorio-Castaño _{1,

2,

3} , Pedro Arias _{1,

2} , Alberto Fernández-Jaén ₄ , Guillermo Lay-Son ₅ , Gloria Bueno-Lozano ₆ , Allan Bayat ₇ , Laurence Faivre _{3,

8,

9} , Natalia Gallego _{1,

2,

3} , Sergio Ramos _{1,

2} , Kameryn M Butler ₁₀ , Chantal Morel _{11,

12} , Stasia Hadjiyannakis ₁₃ , James Lespinasse ₁₄ , Frederic Tran-Mau-Them ₁₅ , Fernando Santos-Simarro _{1,

3,

16} , Lucile Pinson ₁₇ , Antonio Federico Martínez-Monseny _{18,

19} , María Del Mar O'Callaghan Cord ₁₈ , Sara Álvarez ₂₀ , Elliot S Stolerman ₁₀ , Camerun Washington ₁₀ , Feliciano J Ramos _{1,

6,

21} , The S O G R I Consortium _{1,

2} , Pablo Lapunzina _{1,

2,

3}

Affiliation

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.

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.

中文翻译：

Tenorio 综合征：14 例新病例的描述和临床和分子特征的回顾

Tenorio 综合征 (TNORS) (OMIM #616260) 是一种相对较新的疾病，迄今为止描述的病例很少。临床特征包括大头畸形、智力障碍、肌张力减退、脑室扩大和自身免疫性疾病。分子潜在机制显示错义变异和包含RNF125的大缺失，RNF125是编码 U3 泛素连接酶蛋白的基因。自从对来自四个家庭的六名患者的疾病进行初步描述以来，诊断出几名新患者，为临床谱增加了更多证据。在本文中，我们描述了另外 14 个具有深度表型分析的病例，并对所有具有RNF125致病变异的病例进行了全面回顾. 并非所有患者都出现过度生长，但相反，大多数患者表现出神经发育疾病、大头畸形和/或前额大的常见模式。分离分析表明，尽管某些患者的变异是从明显无症状的父母那里遗传的，但深度表型分析表明其中一些患者患有轻度疾病。这种疾病发展的潜在机制尚不清楚，进一步病例的报告将有助于更好地理解和临床表征该综合征。

更新日期：2021-09-03

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