Autoimmune cytopenia and Kabuki syndrome in paediatrics: Insights in 11 patients.
Evans syndrome
Kabuki syndrome
childhood ITP
immune thrombocytopenic purpura
inherited errors of immunity
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
03 Mar 2024
03 Mar 2024
Historique:
revised:
16
02
2024
received:
02
02
2024
accepted:
24
02
2024
medline:
4
3
2024
pubmed:
4
3
2024
entrez:
3
3
2024
Statut:
aheadofprint
Résumé
Kabuki syndrome (KS) is now listed in the Human Inborn Errors of Immunity (IEI) Classification. It is a rare disease caused by KMT2D and KDM6A variants, dominated by intellectual disability and characteristic facial features. Recurrently, pathogenic variants are identified in those genes in patients examined for autoimmune cytopenia (AIC), but interpretation remains challenging. This study aims to describe the genetic diagnosis and the clinical management of patients with paediatric-onset AIC and KS. Among 11 patients with AIC and KS, all had chronic immune thrombocytopenic purpura, and seven had Evans syndrome. All had other associated immunopathological manifestations, mainly symptomatic hypogammaglobinaemia. They had a median of 8 (5-10) KS-associated manifestations. Pathogenic variants were detected in KMT2D gene without clustering, during the immunological work-up of AIC in three cases, and the clinical strategy to validate them is emphasized. Eight patients received second-line treatments, mainly rituximab and mycophenolate mofetil. With a median follow-up of 17 (2-31) years, 8/10 alive patients still needed treatment for AIC. First-line paediatricians should be able to recognize and confirm KS in children with ITP or multiple AIC, to provide early appropriate clinical management and specific long-term follow-up. The epigenetic immune dysregulation in KS opens exciting new perspectives.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Association Française du Syndrome d'Evans (AFSE), the O-CYTO patients' association
Organisme : Ministère de la Santé
Organisme : Association pour la Recherche et les Maladies Hématologiques de l'Enfant (RMHE) research charity
Informations de copyright
© 2024 British Society for Haematology and John Wiley & Sons Ltd.
Références
Niikawa N, Kuroki Y, Kajii T, Matsuura N, Ishikiriyama S, Tonoki H, et al. Kabuki make-up (Niikawa-Kuroki) syndrome: a study of 62 patients. Am J Med Genet. 1988;31:565-589. https://doi.org/10.1002/ajmg.1320310312
Niikawa N, Matsuura N, Fukushima Y, Ohsawa T, Kajii T. Kabuki make-up syndrome: a syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency. J Pediatr. 1981;99:565-569. https://doi.org/10.1016/s0022-3476(81)80255-7
Kuroki Y, Suzuki Y, Chyo H, Hata A, Matsui I. A new malformation syndrome of long palpebralfissures, large ears, depressed nasal tip, and skeletal anomalies associated with postnatal dwarfism and mental retardation. J Pediatr. 1981;99:570-573. https://doi.org/10.1016/S0022-3476(81)80256-9
Adam MP, Hudgins L, Hannibal M. Kabuki Syndrome. Seattle: University of Washington; 2022.
Di Candia F, Fontana P, Paglia P, Falco M, Rosano C, Piscopo C, et al. Clinical heterogeneity of kabuki syndrome in a cohort of Italian patients and review of the literature. Eur J Pediatr. 2022;181:171-187. https://doi.org/10.1007/s00431-021-04108-w
Wessels MW, Brooks AS, Hoogeboom J, Niermeijer MF, Willems PJ. Kabuki syndrome: a review study of three hundred patients. Clin Dysmorphol. 2002;11:95-102. https://doi.org/10.1097/00019605-200204000-00004
Adam MP, Banka S, Bjornsson HT, Bodamer O, Chudley AE, Harris J, et al. Kabuki syndrome: international consensus diagnostic criteria. J Med Genet. 2019;56:89-95. https://doi.org/10.1136/jmedgenet-2018-105625
Margot H, Boursier G, Duflos C, Sanchez E, Amiel J, Andrau J-C, et al. Immunopathological manifestations in Kabuki syndrome: a registry study of 177 individuals. Genet Med. 2020;22:181-188. https://doi.org/10.1038/s41436-019-0623-x
Tangye SG, Al-Herz W, Bousfiha A, Cunningham-Rundles C, Franco JL, Holland SM, et al. Human inborn errors of immunity: 2022 update on the classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol. 2022;42:1473-1507. https://doi.org/10.1007/s10875-022-01289-3
Hadjadj J, Aladjidi N, Fernandes H, Leverger G, Magérus-Chatinet A, Mazerolles F, et al. Pediatric Evans syndrome is associated with a high frequency of potentially damaging variants in immune genes. Blood. 2019;134:9-21. https://doi.org/10.1182/blood-2018-11-887141
Aladjidi N, Leverger G, Leblanc T, Picat MQ, Michel G, Bertrand Y, et al. New insights into childhood autoimmune hemolytic anemia: a French national observational study of 265 children. Haematologica. 2011;96:655-663. https://doi.org/10.3324/haematol.2010.036053
Aladjidi N, Jutand MA, Beaubois C, Fernandes H, Jeanpetit J, Coureau G, et al. Reliable assessment of the incidence of childhood autoimmune hemolytic anemia. Pediatr Blood Cancer. 2017;64:e26683. https://doi.org/10.1002/pbc.26683
Ming JE, Russell KL, McDonald-McGinn DM, Zackai EH. Autoimmune disorders in Kabuki syndrome: Autoimmune Disorders in Kabuki Syndrome. Am J Med Genet. 2005;132A:260-262. https://doi.org/10.1002/ajmg.a.30332
Giordano P, Lassandro G, Sangerardi M, Faienza MF, Valente F, Martire B. Autoimmune haematological disorders in two Italian children with kabuki syndrome. Ital J Pediatr. 2014;40:10. https://doi.org/10.1186/1824-7288-40-10
Torii Y, Yagasaki H, Tanaka H, Mizuno S, Nishio N, Muramatsu H, et al. Successful treatment with rituximab of refractory idiopathic thrombocytopenic purpura in a patient with kabuki syndrome. Int J Hematol. 2009;90:174-176. https://doi.org/10.1007/s12185-009-0387-1
Watanabe T, Miyakawa M, Satoh M, Abe T, Oda Y. Kabuki make-up syndrome associated with chronic idiopathic thrombocytopenic purpura. Pediatr Int. 1994;36:727-729. https://doi.org/10.1111/j.1442-200X.1994.tb03281.x
Schiavo E, Martini B, Attardi E, Consonni F, Ciullini Mannurita S, Coniglio ML, et al. Autoimmune Cytopenias and dysregulated Immunophenotype act as warning signs of inborn errors of immunity: results from a prospective study. Front Immunol. 2021;12:790455. https://doi.org/10.3389/fimmu.2021.790455
Kim Y, Shim YJ, Kim DH, Ha JS, Jung HR. Autoimmune cytopenia in a Korean pediatric patient with Kabuki syndrome treated with sirolimus. Pediatr Blood Cancer. 2023;70:e30275. https://doi.org/10.1002/pbc.30275
Okano T, Imai K, Naruto T, Okada S, Yamashita M, Yeh T, et al. Whole-exome sequencing-based approach for germline mutations in patients with inborn errors of immunity. J Clin Immunol. 2020;40:729-740. https://doi.org/10.1007/s10875-020-00798-3
Wang J, Liao J, Zhang J, Cheng W-Y, Hakenberg J, Ma M, et al. ClinLabGeneticist: a tool for clinical management of genetic variants from whole exome sequencing in clinical genetic laboratories. Genome Med. 2015;7:77. https://doi.org/10.1186/s13073-015-0207-6
Kopanos C, Tsiolkas V, Kouris A, Chapple CE, Albarca Aguilera M, Meyer R, et al. VarSome: the human genomic variant search engine. Bioinformatics. 2019;35:1978-1980. https://doi.org/10.1093/bioinformatics/bty897
Coulter TI, Chandra A, Bacon CM, Babar J, Curtis J, Screaton N, et al. Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: a large patient cohort study. J Allergy Clin Immunol. 2017;139:597-606.e4. https://doi.org/10.1016/j.jaci.2016.06.021
Savoia A, Pecci A. MYH9-related disease. Seattle: University of Washington; 2021.
Pecci A, Klersy C, Gresele P, Lee KJD, De Rocco D, Bozzi V, et al. MYH9-related disease: a novel prognostic model to predict the clinical evolution of the disease based on genotype-phenotype correlations. Hum Mutat. 2014;35:236-247. https://doi.org/10.1002/humu.22476
Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113:2386-2393.
Heitink-Polle KM, Nijsten J, Boonacker CW, de Haas M, Bruin MC. Clinical and laboratory predictors of chronic immune thrombocytopenia in children: a systematic review and meta-analysis. Blood. 2014;124:3295-3307.
Todoric K, Koontz JB, Mattox D, Tarrant TK. Autoimmunity in immunodeficiency. Curr Allergy Asthma Rep. 2013;13:361-370. https://doi.org/10.1007/s11882-013-0350-3
Stagi S, Gulino AV, Lapi E, Rigante D. Epigenetic control of the immune system: a lesson from kabuki syndrome. Immunol Res. 2016;64:345-359. https://doi.org/10.1007/s12026-015-8707-4
Kim TO, Despotovic JM. Primary and secondary immune Cytopenias: evaluation and treatment approach in children. Hematol Oncol Clin North Am. 2019;33:489-506. https://doi.org/10.1016/j.hoc.2019.01.005
Cantoni S, Fattizzo B. Clinical course and management of adult-onset immune-mediated cytopenia associated with kabuki syndrome. Eur J Intern Med. 2019;69:e3-e5. https://doi.org/10.1016/j.ejim.2019.08.003
Vianelli N, Auteri G, Buccisano F, Carrai V, Baldacci E, Clissa C, et al. Refractory primary immune thrombocytopenia (ITP): current clinical challenges and therapeutic perspectives. Ann Hematol. 2022;101:963-978. https://doi.org/10.1007/s00277-022-04786-y
Pincez T, Aladjidi N, Heritier S, Garnier N, Fahd M, Abou Chahla W, et al. Determinants of splenectomy long-term outcomes in pediatric autoimmune cytopenias. Blood. 2022;140:253-261. https://doi.org/10.1182/blood.2022015508
Kerr B, Murphy P, Quinn J. Refractory ITP in a patient with Kabuki syndrome: response to low-dose rituximab. Int J Hematol. 2017;105:702-703. https://doi.org/10.1007/s12185-016-2176-y
HAS. Protocole national de diagnostic et de soins (PNDS) Purpura thrombopénique immunologique de l'enfant et de l'adulte 2017.
Miano M, Ramenghi U, Russo G, Rubert L, Barone A, Tucci F, et al. Mycophenolate mofetil for the treatment of children with immune thrombocytopenia and Evans syndrome. A retrospective data review from the Italian association of paediatric haematology/oncology. Br J Haematol. 2016;175:490-495. https://doi.org/10.1111/bjh.14261
Pell J, Greenwood R, Ingram J, Wale K, Thomas I, Kandiyali R, et al. Trial protocol: a multicentre randomised trial of first-line treatment pathways for newly diagnosed immune thrombocytopenia: standard steroid treatment versus combined steroid and mycophenolate. The FLIGHT Trial BMJ Open. 2018;8:e024427. https://doi.org/10.1136/bmjopen-2018-024427
Lee MG, Villa R, Trojer P, Norman J, Yan K-P, Reinberg D, et al. Demethylation of H3K27 regulates Polycomb recruitment and H2A ubiquitination. Science. 2007;318:447-450. https://doi.org/10.1126/science.1149042
Smith E, Lin C, Shilatifard A. The super elongation complex (SEC) and MLL in development and disease. Genes Dev. 2011;25:661-672. https://doi.org/10.1101/gad.2015411
Aref-Eshghi E, Kerkhof J, Pedro VP, Barat-Houari M, Ruiz-Pallares N, Andrau J-C, et al. Evaluation of DNA methylation Episignatures for diagnosis and phenotype correlations in 42 mendelian neurodevelopmental disorders. Am J Hum Genet. 2020;106:356-370. https://doi.org/10.1016/j.ajhg.2020.01.019
Aref-Eshghi E, Schenkel LC, Lin H, Skinner C, Ainsworth P, Paré G, et al. The defining DNA methylation signature of kabuki syndrome enables functional assessment of genetic variants of unknown clinical significance. Epigenetics. 2017;12:923-933. https://doi.org/10.1080/15592294.2017.1381807