Autoimmune haematological disorders in two Italian children with Kabuki Syndrome

Italian Journal of Pediatrics

Baldassarre Martire¹  Federica Valente¹  Maria Felicia Faienza¹  Maria Sangerardi¹  Giuseppe Lassandro¹  Paola Giordano¹ 

[1] University of Bari “Aldo Moro”, Department of Biomedical Sciences and Human Oncology, Paediatric Hospital, Piazza Giulio Cesare, 11 – 70124 Bari, Italy

关键词: KDM6A;    MLL2;    KMT2D;    Autoimmune haematological disorders;    Immune thrombocytopenia;    Immune haemolytic anaemia;    Kabuki syndrome;   

Others  :  805111
DOI  :  10.1186/1824-7288-40-10

 received in 2013-08-31, accepted in 2014-01-02,  发布年份 2014

【 摘 要 】

Kabuki syndrome (also called Niikawa-Kuroki syndrome) is a rare genetic disease described for the first time in Japan, characterised by anomalies in multiple organ systems and often associated with autoimmune disorders and impaired immune response. We herein report the clinical history, the therapeutic approach and the outcome of two children with Kabuki syndrome who developed autoimmune haematological disorders (haemolytic anaemia and immune thrombocytopenia). Factors regarding differential diagnosis and interventions in better management of this syndrome and its complications are discussed. This is the first report of Italian children with autoimmune haematological disorders complicating Kabuki syndrome.

【 授权许可】

   
2014 Giordano et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 2.

【 参考文献 】

• [1]Niikawa N, Maatsuura 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.
• [2]Kuroki Y, Suzuki Y, Chyo H, Hata A, Matsui I: A new malformation syndrome of long palpebral fissures, large ears, depressed nasal tip and skeletal anomalies associated with postnatal dwarfism and mental retardation. J Pediatr 1981, 99:570-573.
• [3]Kuroki Y, Katsumata N, Eguchi T, Fukushima Y, Suwa S, Kajii T: Precocious puberty in Kabuki makeup syndrome. J Pediatr 1987, 110:750-752.
• [4]Micale L, Augello B, Fusco C, Selicorni A, Loviglio MN, Silengo MC, Reymond A, Gumiero B, Zucchetti F, D’Addetta EV, Belligni E, Calcagnì A, Digilio MC, Dallapiccola B, Faravelli F, Forzano F, Accadia M, Bonfante A, Clementi M, Daolio C, Douzgou S, Ferrari P, Fischetto R, Garavelli L, Lapi E, Mattina T, Melis D, Patricelli MG, Priolo M, Prontera P, et al.: Mutation spectrum of MLL2 in a cohort of Kabuki syndrome patients. Orphanet J Rare Dis 2011, 9:6-38.
• [5]Bokinni Y: Kabuki syndrome revisited. J Human Genet 2012, 57(4):223-227.
• [6]McGaugharan J, Aftimos S, Jefferies C, Winship I: Clinical phenotypes of nine cases of Kabuki syndrome from New Zealand. Clin Dysmorphol 2001, 10:257-262.
• [7]Niikawa N, Kuroki Y, Kajii T, Matsuura N, Ishikiriyama S, Tonoki H, Ishikawa N, Yamada Y, Fujita M, Umemoto H: Kabuki make-up (Niikawa-Kuroki) syndrome: a study of 62 patients. Am J Med Genet 1988, 31:565-589.
• [8]Wilson GN: Thirteen cases of Niikawa-Kuroki syndrome: report and review with emphasis on medical complications and preventative management. Am J Med Genet 1998, 79:112.
• [9]Kawame H, Hannibal MC, Hudgins L, Pagon RA: Phenotypic spectrum and management issues in Kabuki syndrome. J Pediatr 1999, 134:480-485.
• [10]Matsumoto N, Niikawa N: Kabuki make-up syndrome: a review. Am J Med Genet C Semin Med Genet 2003, 117:57-65.
• [11]Armstrong L, Abd El Moneim A, Aleck K, Aughton DJ, Baumann C, Braddock SR, Gillessen-Kaesbach G, Graham JM Jr, Grebe TA, Gripp KW, Hall BD, Hennekam R, Hunter A, Keppler-Noreuil K, Lacombe D, Lin AE, Ming JE, Kokitsu-Nakata NM, Nikkel SM, Philip N, Raas-Rothschild A, Sommer A, Verloes A, Walter C, Wieczorek D, Williams MS, Zackai E, Allanson JE: Further delineation of Kabuki syndrome in 48 well-defined new individuals. Am J Med Genet A 2005, 132:265-272.
• [12]Schrander-Stumpel CT, Spruyt L, Curfs LM, Defloor T, Schrander JJ, Kabuki syndrome: Clinical data in 20 patients, literature review, and further guidelines for preventive management. Am J Med Genet A 2005, 132A:234-243.
• [13]Banka S, Veeramachaneni R, Reardon W, Howard E, Bunstone S, Ragge N, Parker MJ, Crow YJ, Kerr B, Kingston H, Metcalfe K, Chandler K, Magee A, Stewart F, McConnell VP, Donnelly DE, Berland S, Houge G, Morton JE, Oley C, Revencu N, Park SM, Davies SJ, Fry AE, Lynch SA, Gill H, Schweiger S, Lam WW, Tolmie J, Mohammed SN, et al.: How genetically heterogeneous is Kabuki syndrome? MLL2 testing in 116 patients, review, and analyses of mutation and phenotypic spectrum. Eur J Hum Genet 2012, 20:381-388.
• [14]Dillon S, Zhang X, Trievel R, Cheng X: The SET-domain protein superfamily: protein lysine methyltransferase. Genome Biol 2005, 6:227.
• [15]Guo C, Chen LH, Huang Y, Chang CC, Wang P, Pirozzi CJ, Qin X, Bao X, Greer PK, McLendon RE, Yan H, Keir ST, Bigner DD, He Y: KMT2D maintains neoplastic cell proliferation and global histone H3 lysine 4 monomethylation. Oncotarget 2013, 4:2144-2153.
• [16]Lederer D, Grisart B, Digilio MC, Benoit V, Crespin M, Ghariani SC, Maystadt I, Dallapiccola B, Verellen-Dumoulin C: Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome. The Am J Hum Genet 2012, 90:119-124.
• [17]Miyake N, Mizuno S, Okamoto N, Ohashi H, Shiina M, Ogata K, Tsurusaki Y, Nakashima M, Saitsu H, Niikawa N, Matsumoto N: KDM6A point mutations cause Kabuki syndrome. Hum Mutation 2013, 34:108-110.
• [18]Lee MG, Villa R, Trojer P, Norman J, Yan KP, Reinberg D, Di Croce L, Shiekhattar R: Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination. Science 2007, 318:447-450.
• [19]Miyake N, Koshimizu E, Okamoto N, Mizuno S, Ogata T, Nagai T, Kosho T, Ohashi H, Kato M, Sasaki G, Mabe H, Watanabe Y, Yoshino M, Matsuishi T, Takanashi J, Shotelersuk V, Tekin M, Ochi N, Kubota M, Ito N, Ihara K, Hara T, Tonoki H, Ohta T, Saito K, Matsuo M, Urano M, Enokizono T, Sato A, Tanaka H, et al.: MLL2 and KDM6A mutations in patients with Kabuki syndrome. Am J Med Genet A 2013, 61:2234-2243.
• [20]Clayton-Smith J: Kabuki syndrome clinical management guidelines. http://kabukisyndrome.com/content/management-kabuki-syndrome webcite
• [21]Hoffman JD, Ciprero KL, Sullivan KE, Kaplan PB, McDonald-McGinn DM, Zackai EH, Ming JE: Immune abnormalities are a frequent manifestation of Kabuki syndrome. Am J Med Genet A 2005, 135:278-81.
• [22]Ming JE, Russel KL, McDonald-McGinn DM, Zackai EH: Autoimmune disorders in Kabuki syndrome. Am J Med Genet A 2005, 132A:260-262.
• [23]Ng SB, Bigham AW, Buckingham KJ, Hannibal MC, McMillin MJ, Gildersleeve HI, Beck AE, Tabor HK, Cooper GM, Mefford HC, Lee C, Turner EH, Smith JD, Rieder MJ, Yoshiura K, Matsumoto N, Ohta T, Niikawa N, Nickerson DA, Bamshad MJ, Shendure J: Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Gent 2010, 42:790-793.
• [24]Priolo M, Micale L, Augello B, Fusco C, Zucchetti F, Prontera P, Paduano V, Biamino E, Selicorni A, Mammì C, Laganà C, Zelante L, Merla G: Absence of deletion and duplication of MLL2 and KDM6A genes in a large cohort of patients with Kabuki syndrome. Mol Genet Metab 2012, 107:627-629.
• [25]Cunningham-Rundles C: Common variable immunodeficiency. Curr Allergy Asthma Rep 2001, 1:421-429.
• [26]Gennery AR, Barge D, O’Sullivan JJ, Flood TJ, Abinun M, Cant AJ: Antibody deficiency and autoimmunity in 22q11.2 deletion syndrome. Arch Dis Child 2002, 86:422-425.
• [27]Jawad AF, McDonald-McGinn DM, Zackai EH, Sullivan KE: Immunological features of chromosome 22q11.2 deletion syndrome. J Pediatr 2001, 139:715-723.
• [28]Sullivan KE, McDonald-McGinn DM, Driscoll DA, Zmijewski CM, Ellaban AS, Reed L, Emanuel BS, Zackai EH, Athreya BH, Keenan G: Juvenile rheumatoid arthritis-like poltarthritis in chromosome 22q11.2 deletion syndrome. Arthritis Rheum 1997, 40:430-436.
• [29]DePiero AD, Lourie EM, Berman BW, Robin NH, Zinn AB, Hostoffer RW: Recurrent immune cytopenias in two patients with DiGeorge/velocardiofacial syndrome. J Pediatr 1997, 131:484-486.
• [30]Kawame H, Adachi M, Tachibana K, Kurosawa K, Ito F, Gleason MM, Weinzimer S, Levitt-Katz L, Sullivan K, McDonald-McGinn DM: Graves’ disease in patients with 22q11.2 deletion. J Pediatr 2001, 139:892-895.
• [31]Delvecchio M, De Bellis A, De Mattia D, Cavallo L, Martire B: Growth hormone deficiency and antipituitary antibodies in a patient with common variable immunodeficiency. J Endocrinol Invest 2009, 32:637-40.
• [32]Martire B, Burattini MG, De Santis A, Schettini F Jr, De Mattia D: Benign lymphoproliferation syndrome, autoimmune neutropenia and thrombocytopenia in partial Di George syndrome: efficacy of rh G-CSF and prednisone. Acta Pediatr 2001, 90:821-3.
• [33]Martire B, Gentile A, Francavilla R, De Santis A, De Mattia D: Successful treatment with cyclosporine A of HCV-driven chronic liver disease mimicking autoimmune hepatitis in a patient with common variable immunodeficiency. Immunopharmacol Immunotoxicol 2005, 27:535-43.
• [34]Davies GE: Immunodeficiency in DiGeorge syndrome and options for treating cases with complete athymia. Front Immunol 2013, 4:322.
• [35]Torii Y, Yagasaki H, Tanaka H, Mizuno S, Nishio N, Muramatsu H, Hama A, Takahashi Y, Kojima S: Successful treatment with Rituximab of refractory idiopathic thrombocytopenic purpura in a patient with Kabuki syndrome. Int J Hematol 2009, 90:174-6.
• [36]Seif AE, Manno CS, Sheen C, Grupp SA, Teachey DT: Identifying autoimmune lymphoproliferative syndrome in children with Evans syndrome: a multi-istitutional study. Bloodl 2010, 115:2142-45.
• [37]Guidelines of paediatric oncology and haematology Italian association http://www.aieop.org/?q=lineeguida.html webcite
• [38]French kabuki syndrome network. Epidemiology, management of patients and research by array-CGH http://clinicaltrials.gov/show/NCT01314534 webcite