Kabuki syndrome

International consensus diagnostic criteria

Margaret P. Adam, Siddharth Banka, Hans Tomas Bjornsson, Olaf Bodamer, Albert E. Chudley, Jaqueline Harris, Hiroshi Kawame, Brendan C. Lanpher, Andrew W. Lindsley, Giuseppe Merla, Noriko Miyake, Nobuhiko Okamoto, Constanze T. Stumpel, Norio Niikawa

Research output: Contribution to journalArticle

Abstract

Background: Kabuki syndrome (KS) is a clinically recognisable syndrome in which 70% of patients have a pathogenic variant in KMT2D or KDM6A. Understanding the function of these genes opens the door to targeted therapies. The purpose of this report is to propose diagnostic criteria for KS, particularly when molecular genetic testing is equivocal. Methods: An international group of experts created consensus diagnostic criteria for KS. Systematic PubMed searches returned 70 peer-reviewed publications in which at least one individual with molecularly confirmed KS was reported. The clinical features of individuals with known mutations were reviewed. Results: The authors propose that a definitive diagnosis can be made in an individual of any age with a history of infantile hypotonia, developmental delay and/or intellectual disability, and one or both of the following major criteria: (1) a pathogenic or likely pathogenic variant in KMT2D or KDM6A; and (2) typical dysmorphic features (defined below) at some point of life. Typical dysmorphic features include long palpebral fissures with eversion of the lateral third of the lower eyelid and two or more of the following: (1) arched and broad eyebrows with the lateral third displaying notching or sparseness; (2) short columella with depressed nasal tip; (3) large, prominent or cupped ears; and (4) persistent fingertip pads. Further criteria for a probable and possible diagnosis, including a table of suggestive clinical features, are presented. Conclusion: As targeted therapies for KS are being developed, it is important to be able to make the correct diagnosis, either with or without molecular genetic confirmation.

Original languageEnglish (US)
JournalJournal of Medical Genetics
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Consensus
Molecular Biology
Nictitating Membrane
Eyebrows
Developmental Disabilities
Muscle Hypotonia
Genetic Testing
Eyelids
Nose
PubMed
Intellectual Disability
Ear
Publications
Kabuki syndrome
Mutation
Therapeutics
Genes

Keywords

  • consensus diagnostic criteria
  • kabuki make-up syndrome
  • kabuki syndrome
  • Kdm6a
  • Kmt2d

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Adam, M. P., Banka, S., Bjornsson, H. T., Bodamer, O., Chudley, A. E., Harris, J., ... Niikawa, N. (Accepted/In press). Kabuki syndrome: International consensus diagnostic criteria. Journal of Medical Genetics. https://doi.org/10.1136/jmedgenet-2018-105625

Kabuki syndrome : International consensus diagnostic criteria. / Adam, Margaret P.; Banka, Siddharth; Bjornsson, Hans Tomas; Bodamer, Olaf; Chudley, Albert E.; Harris, Jaqueline; Kawame, Hiroshi; Lanpher, Brendan C.; Lindsley, Andrew W.; Merla, Giuseppe; Miyake, Noriko; Okamoto, Nobuhiko; Stumpel, Constanze T.; Niikawa, Norio.

In: Journal of Medical Genetics, 01.01.2018.

Research output: Contribution to journalArticle

Adam, MP, Banka, S, Bjornsson, HT, Bodamer, O, Chudley, AE, Harris, J, Kawame, H, Lanpher, BC, Lindsley, AW, Merla, G, Miyake, N, Okamoto, N, Stumpel, CT & Niikawa, N 2018, 'Kabuki syndrome: International consensus diagnostic criteria', Journal of Medical Genetics. https://doi.org/10.1136/jmedgenet-2018-105625
Adam, Margaret P. ; Banka, Siddharth ; Bjornsson, Hans Tomas ; Bodamer, Olaf ; Chudley, Albert E. ; Harris, Jaqueline ; Kawame, Hiroshi ; Lanpher, Brendan C. ; Lindsley, Andrew W. ; Merla, Giuseppe ; Miyake, Noriko ; Okamoto, Nobuhiko ; Stumpel, Constanze T. ; Niikawa, Norio. / Kabuki syndrome : International consensus diagnostic criteria. In: Journal of Medical Genetics. 2018.
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AU - Adam, Margaret P.

AU - Banka, Siddharth

AU - Bjornsson, Hans Tomas

AU - Bodamer, Olaf

AU - Chudley, Albert E.

AU - Harris, Jaqueline

AU - Kawame, Hiroshi

AU - Lanpher, Brendan C.

AU - Lindsley, Andrew W.

AU - Merla, Giuseppe

AU - Miyake, Noriko

AU - Okamoto, Nobuhiko

AU - Stumpel, Constanze T.

AU - Niikawa, Norio

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N2 - Background: Kabuki syndrome (KS) is a clinically recognisable syndrome in which 70% of patients have a pathogenic variant in KMT2D or KDM6A. Understanding the function of these genes opens the door to targeted therapies. The purpose of this report is to propose diagnostic criteria for KS, particularly when molecular genetic testing is equivocal. Methods: An international group of experts created consensus diagnostic criteria for KS. Systematic PubMed searches returned 70 peer-reviewed publications in which at least one individual with molecularly confirmed KS was reported. The clinical features of individuals with known mutations were reviewed. Results: The authors propose that a definitive diagnosis can be made in an individual of any age with a history of infantile hypotonia, developmental delay and/or intellectual disability, and one or both of the following major criteria: (1) a pathogenic or likely pathogenic variant in KMT2D or KDM6A; and (2) typical dysmorphic features (defined below) at some point of life. Typical dysmorphic features include long palpebral fissures with eversion of the lateral third of the lower eyelid and two or more of the following: (1) arched and broad eyebrows with the lateral third displaying notching or sparseness; (2) short columella with depressed nasal tip; (3) large, prominent or cupped ears; and (4) persistent fingertip pads. Further criteria for a probable and possible diagnosis, including a table of suggestive clinical features, are presented. Conclusion: As targeted therapies for KS are being developed, it is important to be able to make the correct diagnosis, either with or without molecular genetic confirmation.

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