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J Pediatr Genet 2021; 10(01): 049-052
DOI: 10.1055/s-0040-1701645
Case Report

Facial Dysmorphisms, Macrodontia, Focal Epilepsy, and Thinning of the Corpus Callosum: A Rare Mild Form of Kabuki Syndrome

Valentina Bruni
1   Pediatric Unit, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
,
Cristina Scozzafava
1   Pediatric Unit, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
,
Maria Gnazzo
2   Laboratory of Medical Genetics, IRCCS, Bambino Gesù Children's Hospital, Rome, Italy
,
Francesca Parisi
1   Pediatric Unit, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
,
Simona Sestito
1   Pediatric Unit, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
,
Licia Pensabene
1   Pediatric Unit, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
,
Antonio Novelli
2   Laboratory of Medical Genetics, IRCCS, Bambino Gesù Children's Hospital, Rome, Italy
,
Daniela Concolino 
1   Pediatric Unit, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
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Abstract

Kabuki syndrome (KS) is a rare genetic condition with multiple congenital abnormalities and developmental delay. The cardinal manifestations of KS include characteristic facial features, intellectual disability, skeletal defects, dermatoglyphic abnormalities, and postnatal growth deficiencies. Cardiac and urological malformations are commonly present in patient with KS, as well as language deficits and immunological abnormalities. Here, we reported a case of a child with an atypical form of KS, associated with macrodontia, corpus callosum dysmorphism, focal epilepsy responsive to antiepileptic treatment, and a novel KMT2D gene missense variant, c.2413C > T, never reported to date.

Keywords

Kabuki syndrome - KMT2D gene - focal epilepsy


Publication History

Received: 01 October 2019

Accepted: 10 January 2020

Article published online:
17 February 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
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  • References

  • 1 Matsumoto N, Niikawa N. Kabuki make-up syndrome: a review. Am J Med Genet C Semin Med Genet 2003; 117C (01) 57-65
    CrossrefPubMedGoogle Scholar
  • 2 Adam MP, Hudgins L. Kabuki syndrome: a review. Clin Genet 2005; 67 (03) 209-219
    CrossrefPubMedGoogle Scholar
  • 3 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 (04) 570-573
    CrossrefPubMedGoogle Scholar
  • 4 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
    CrossrefPubMedGoogle Scholar
  • 5 Hoffman JD, Ciprero KL, Sullivan KE. et al. Immune abnormalities are a frequent manifestation of Kabuki syndrome. Am J Med Genet A 2005; 135 (03) 278-281
    CrossrefPubMedGoogle Scholar
  • 6 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 (04) 565-569
    CrossrefPubMedGoogle Scholar
  • 7 Niikawa N, Kuroki Y, Kajii T. et al. Kabuki make-up (Niikawa-Kuroki) syndrome: a study of 62 patients. Am J Med Genet 1988; 31 (03) 565-589
    CrossrefPubMedGoogle Scholar
  • 8 Froimchuk E, Jang Y, Ge K. Histone H3 lysine 4 methyltransferase KMT2D. Gene 2017; 627: 337-342
    CrossrefPubMedGoogle Scholar
  • 9 Shilatifard A. Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation. Curr Opin Cell Biol 2008; 20 (03) 341-348
    CrossrefPubMedGoogle Scholar
  • 10 Zhang J, Dominguez-Sola D, Hussein S. et al. Disruption of KMT2D perturbs germinal center B cell development and promotes lymphomagenesis. Nat Med 2015; 21 (10) 1190-1198
    CrossrefPubMedGoogle Scholar
  • 11 Ortega-Molina A, Boss IW, Canela A. et al. The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development. Nat Med 2015; 21 (10) 1199-1208
    CrossrefPubMedGoogle Scholar
  • 12 Toska E, Osmanbeyoglu HU, Castel P. et al. PI3K pathway regulates ER-dependent transcription in breast cancer through the epigenetic regulator KMT2D. Science 2017; 355 (6331): 1324-1330
    CrossrefPubMedGoogle Scholar
  • 13 Bjornsson HT, Benjamin JS, Zhang L. et al. Histone deacetylase inhibition rescues structural and functional brain deficits in a mouse model of Kabuki syndrome. Sci Transl Med 2014; 6 (256) 256ra135
    CrossrefPubMedGoogle Scholar
  • 14 Micale L, Augello B, Maffeo C. et al. Molecular analysis, pathogenic mechanisms, and readthrough therapy on a large cohort of Kabuki syndrome patients. Hum Mutat 2014; 35 (07) 841-850
    CrossrefPubMedGoogle Scholar
  • 15 Ng SB, Bigham AW, Buckingham KJ. et al. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Genet 2010; 42 (09) 790-793
    CrossrefPubMedGoogle Scholar
  • 16 Kim SJ, Cho SY, Maeng SH. et al. A novel MLL2 gene mutation in a Korean patient with Kabuki syndrome. Korean J Pediatr 2013; 56 (08) 355-358
    CrossrefPubMedGoogle Scholar
  • 17 Cocciadiferro D, Augello B, De Nittis P. et al. Dissecting KMT2D missense mutations in Kabuki syndrome patients. Hum Mol Genet 2018; 27 (21) 3651-3668
    CrossrefPubMedGoogle Scholar
  • 18 Cheon CK, Ko JM. Kabuki syndrome: clinical and molecular characteristics. Korean J Pediatr 2015; 58 (09) 317-324
    CrossrefPubMedGoogle Scholar
  • 19 Kawame H, Hannibal MC, Hudgins L, Pagon RA. Phenotypic spectrum and management issues in Kabuki syndrome. J Pediatr 1999; 134 (04) 480-485
    CrossrefPubMedGoogle Scholar
  • 20 Philip N, Meinecke P, David A. et al. Kabuki make-up (Niikawa-Kuroki) syndrome: a study of 16 non-Japanese cases. Clin Dysmorphol 1992; 1 (02) 63-77
    CrossrefPubMedGoogle Scholar
  • 21 Bekircan-Kurt CE, Şimşek-Kiper PO, Boduroğlu K, Dericioğlu N. A novel de novo mutation involving the MLL2 gene in a Kabuki syndrome patient presenting with seizures. Turk J Pediatr 2016; 58 (01) 97-100
    CrossrefPubMedGoogle Scholar
  • 22 Lodi M, Chifari R, Parazzini C. et al. Seizures and EEG pattern in Kabuki syndrome. Brain Dev 2010; 32 (10) 829-834
    CrossrefPubMedGoogle Scholar
  • 23 Kurahashi N, Miyake N, Mizuno S. et al. Characteristics of epilepsy in patients with Kabuki syndrome with KMT2D mutations. Brain Dev 2017; 39 (08) 672-677
    CrossrefPubMedGoogle Scholar
  • 24 Ogawa A, Yasumoto S, Tomoda Y, Ohfu M, Mitsudome A, Kuroki Y. Favorable seizure outcome in Kabuki make-up syndrome associated with epilepsy. J Child Neurol 2003; 18 (08) 549-551
    CrossrefPubMedGoogle Scholar
  • 25 Kasuya H, Shimizu T, Nakamura S, Takakura K. Kabuki make-up syndrome and report of a case with hydrocephalus. Childs Nerv Syst 1998; 14 (06) 230-235
    CrossrefPubMedGoogle Scholar
  • 26 Di Gennaro G, Condoluci C, Casali C, Ciccarelli O, Albertini G. Epilepsy and polymicrogyria in Kabuki make-up (Niikawa-Kuroki) syndrome. Pediatr Neurol 1999; 21 (02) 566-568
    CrossrefPubMedGoogle Scholar