Immunopathological manifestations in Kabuki syndrome: a registry study of 177 individuals

• Published in: Genetics in medicine Vol. 22; no. 1; pp. 181 - 188
• Main Authors: Margot, Henri, Boursier, Guilaine, Duflos, Claire, Sanchez, Elodie, Amiel, Jeanne, Andrau, Jean-Christophe, Arpin, Stéphanie, Brischoux-Boucher, Elise, Boute, Odile, Burglen, Lydie, Caille, Charlotte, Capri, Yline, Collignon, Patrick, Conrad, Solène, Cormier-Daire, Valérie, Delplancq, Geoffroy, Dieterich, Klaus, Dollfus, Hélène, Fradin, Mélanie, Faivre, Laurence, Fernandes, Helder, Francannet, Christine, Gatinois, Vincent, Gerard, Marion, Goldenberg, Alice, Ghoumid, Jamal, Grotto, Sarah, Guerrot, Anne-Marie, Guichet, Agnès, Isidor, Bertrand, Jacquemont, Marie-Line, Julia, Sophie, Khau Van Kien, Philippe, Legendre, Marine, Le Quan Sang, K. H., Leheup, Bruno, Lyonnet, Stanislas, Magry, Virginie, Manouvrier, Sylvie, Martin, Dominique, Morel, Godelieve, Munnich, Arnold, Naudion, Sophie, Odent, Sylvie, Perrin, Laurence, Petit, Florence, Philip, Nicole, Rio, Marlène, Robbe, Julie, Rossi, Massimiliano, Sarrazin, Elisabeth, Toutain, Annick, Van Gils, Julien, Vera, Gabriella, Verloes, Alain, Weber, Sacha, Whalen, Sandra, Sanlaville, Damien, Lacombe, Didier, Aladjidi, Nathalie, Geneviève, David
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2020; Elsevier Limited; Nature Publishing Group
• Subjects: Abnormalities, Multiple - genetics; Abnormalities, Multiple - immunology; Adolescent; Adult; Age; Aged; Anemia; Antibiotics; Autoimmune diseases; Autoimmune Diseases - epidemiology; Biomedical and Life Sciences; Biomedicine; Bronchitis; Child; Child, Preschool; Development Biology; Diabetes; Disease; DNA-Binding Proteins - genetics; Face - abnormalities; Female; Genetic Association Studies; Genetic disorders; Genetics; Genomes; Hematologic Diseases - complications; Hematologic Diseases - genetics; Hematologic Diseases - immunology; Histone Demethylases - genetics; Human Genetics; Humans; Immunoglobulins; Infant; Infant, Newborn; Infections; Intellectual disabilities; Laboratory Medicine; Life Sciences; Male; Middle Aged; Mutation; Neoplasm Proteins - genetics; Prevalence; Primary Immunodeficiency Diseases - epidemiology; Questionnaires; Registries; Severity of Illness Index; Standard deviation; Vestibular Diseases - complications; Vestibular Diseases - genetics; Vestibular Diseases - immunology; Vitiligo; Young Adult; Kabuki syndrome; immunity; KMT2D; KDM6A
• ISSN: 1098-3600; 1530-0366; 1530-0366
• DOI: 10.1038/s41436-019-0623-x

Purpose Kabuki syndrome (KS) (OMIM 147920 and 300867) is a rare genetic disorder characterized by specific facial features, intellectual disability, and various malformations. Immunopathological manifestations seem prevalent and increase the morbimortality. To assess the frequency and severity of the manifestations, we measured the prevalence of immunopathological manifestations as well as genotype–phenotype correlations in KS individuals from a registry. Methods Data were for 177 KS individuals with KDM6A or KMT2D pathogenic variants. Questionnaires to clinicians were used to assess the presence of immunodeficiency and autoimmune diseases both on a clinical and biological basis. Results Overall, 44.1% (78/177) and 58.2% (46/79) of KS individuals exhibited infection susceptibility and hypogammaglobulinemia, respectively; 13.6% (24/177) had autoimmune disease (AID; 25.6% [11/43] in adults), 5.6% (10/177) with ≥2 AID manifestations. The most frequent AID manifestations were immune thrombocytopenic purpura (7.3% [13/177]) and autoimmune hemolytic anemia (4.0% [7/177]). Among nonhematological manifestations, vitiligo was frequent. Immune thrombocytopenic purpura was frequent with missense versus other types of variants ( p  = 0.027). Conclusion The high prevalence of immunopathological manifestations in KS demonstrates the importance of systematic screening and efficient preventive management of these treatable and sometimes life-threatening conditions.