A De Novo KMT2D Mutation in a Girl with Kabuki Syndrome Associated with Endocrine Symptoms: a Case Report

Overview

Journal BMC Med Genet

Publisher Biomed Central

Specialty Genetics

Date 2018 Jun 20

PMID 29914387

Citations 11

Authors

Jung-Eun Moon

Su-Jeong Lee

Cheol Woo Ko

Affiliations

Soon will be listed here.

Abstract

Background: Kabuki syndrome is characterized by distinctive facial features and varying degrees of growth retardation. It leads to malformations in skeletal, urogenital and cardiac structures; moreover, endocrine conditions such as premature thelarche, precocious puberty, growth hormone deficiency, diabetes insipidus, thyroid dysfunction and obesity have been reported. Kabuki syndrome is caused by a heterozygous mutation in the KMT2D or KDM6A genes.

Case Presentation: An 11-year-old girl with the typical facial features of Kabuki syndrome visited our hospital due to her short stature. She was found to have the de novo heterozygous mutation of c.8200C > T, p(Arg2734*) in exon 32 of the KMT2D gene and was diagnosed with Kabuki syndrome. The patient also exhibited endocrine abnormalities such as a constitutional delay of puberty, transiently congenial hypothyroidism, obesity and growth hormone deficiency.

Conclusions: This is a case of a mutation in the KMT2D gene in a girl with Kabuki syndrome who presented with endocrine symptoms (constitutional delay of puberty, hypothyroidism, obesity and growth hormone deficiency).

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References

Froimchuk E, Jang Y, Ge K . Histone H3 lysine 4 methyltransferase KMT2D. Gene. 2017; 627:337-342. PMC: 5546304. DOI: 10.1016/j.gene.2017.06.056. View

Devriendt K, LEMLI L, Craen M, de Zegher F . Growth hormone deficiency and premature thelarche in a female infant with kabuki makeup syndrome. Horm Res. 1995; 43(6):303-6. DOI: 10.1159/000184355. View

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(4):565-9. DOI: 10.1016/s0022-3476(81)80255-7. View

Enns G, Cox V, Mohan G, Rosenthal P, Golabi M . Severe congenital anomalies requiring transplantation in children with Kabuki syndrome. Am J Med Genet. 1998; 80(4):362-7. View

Castronovo V, Kusaka M, Chariot A, Gielen J, Sobel M . Homeobox genes: potential candidates for the transcriptional control of the transformed and invasive phenotype. Biochem Pharmacol. 1994; 47(1):137-43. DOI: 10.1016/0006-2952(94)90447-2. View

Matsumoto N, Niikawa N . Kabuki make-up syndrome: a review. Am J Med Genet C Semin Med Genet. 2003; 117C(1):57-65. DOI: 10.1002/ajmg.c.10020. View

Banka S, Veeramachaneni R, Reardon W, Howard E, Bunstone S, Ragge N . How genetically heterogeneous is Kabuki syndrome?: MLL2 testing in 116 patients, review and analyses of mutation and phenotypic spectrum. Eur J Hum Genet. 2011; 20(4):381-8. PMC: 3306863. DOI: 10.1038/ejhg.2011.220. View

Schott D, Gerver W, Stumpel C . Growth Hormone Therapy in Children with Kabuki Syndrome: 1-year Treatment Results. Horm Res Paediatr. 2017; 88(3-4):258-264. DOI: 10.1159/000479368. View

Xin C, Wang C, Wang Y, Zhao J, Wang L, Li R . Identification of novel KMT2D mutations in two Chinese children with Kabuki syndrome: a case report and systematic literature review. BMC Med Genet. 2018; 19(1):31. PMC: 6389055. DOI: 10.1186/s12881-018-0545-5. View

10.

Kawame H, Hannibal M, Hudgins L, Pagon R . Phenotypic spectrum and management issues in Kabuki syndrome. J Pediatr. 1999; 134(4):480-5. DOI: 10.1016/s0022-3476(99)70207-6. View

11.

White S, Thompson E, Kidd A, Savarirayan R, Turner A, Amor D . Growth, behavior, and clinical findings in 27 patients with Kabuki (Niikawa-Kuroki) syndrome. Am J Med Genet A. 2004; 127A(2):118-27. DOI: 10.1002/ajmg.a.20674. View

12.

Kuroki Y, Katsumata N, Eguchi T, Fukushima Y, Suwa S, Kajii T . Precocious puberty in Kabuki makeup syndrome. J Pediatr. 1987; 110(5):750-2. DOI: 10.1016/s0022-3476(87)80018-5. View

13.

Garcia-Gasca A, Spyropoulos D . Differential mammary morphogenesis along the anteroposterior axis in Hoxc6 gene targeted mice. Dev Dyn. 2000; 219(2):261-76. DOI: 10.1002/1097-0177(2000)9999:9999<::AID-DVDY1048>3.0.CO;2-3. View

14.

Bogershausen N, Wollnik B . Unmasking Kabuki syndrome. Clin Genet. 2012; 83(3):201-11. DOI: 10.1111/cge.12051. View

15.

Schott D, Gerver W, Stumpel C . Growth Hormone Stimulation Tests in Children with Kabuki Syndrome. Horm Res Paediatr. 2016; 86(5):319-324. DOI: 10.1159/000449221. View

16.

Niikawa N, Kuroki Y, Kajii T, Matsuura N, Ishikiriyama S, Tonoki H . Kabuki make-up (Niikawa-Kuroki) syndrome: a study of 62 patients. Am J Med Genet. 1988; 31(3):565-89. DOI: 10.1002/ajmg.1320310312. View

17.

Paulussen A, Stegmann A, Blok M, Tserpelis D, Posma-Velter C, Detisch Y . MLL2 mutation spectrum in 45 patients with Kabuki syndrome. Hum Mutat. 2011; 32(2):E2018-25. DOI: 10.1002/humu.21416. View

18.

Ansari K, Mandal S . Mixed lineage leukemia: roles in gene expression, hormone signaling and mRNA processing. FEBS J. 2010; 277(8):1790-804. DOI: 10.1111/j.1742-4658.2010.07606.x. View

19.

Deroo B, Korach K . Estrogen receptors and human disease. J Clin Invest. 2006; 116(3):561-70. PMC: 2373424. DOI: 10.1172/JCI27987. View

20.

Ohlsson C, Hellberg N, Parini P, Vidal O, Bohlooly-Y M, Bohlooly M . Obesity and disturbed lipoprotein profile in estrogen receptor-alpha-deficient male mice. Biochem Biophys Res Commun. 2000; 278(3):640-5. DOI: 10.1006/bbrc.2000.3827. View