Format

Send to

Choose Destination
J Med Genet. 2019 Feb;56(2):89-95. doi: 10.1136/jmedgenet-2018-105625. Epub 2018 Dec 4.

Kabuki syndrome: international consensus diagnostic criteria.

Author information

1
Division of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA.
2
Manchester Centre for Genomic Medicine, Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
3
Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Health Innovation Manchester, Manchester, UK.
4
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
5
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
6
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
7
Department of Genetics and Molecular Medicine, Landspitali University Hospital, Reykjavik, Iceland.
8
Division of Genetics and Genomics, Department of Medicine, Boston Children's Hospital/Harvard Medical School, Boston, Massachusetts, USA.
9
Division of Genetics and Genomics, Broad Institute of MIT and Harvard University, Cambridge, Massachusetts, USA.
10
Department of Pediatrics and Child Health, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
11
Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
12
Departments of Neurology and Pediatrics, Kennedy Krieger Institute, Baltimore, Maryland, USA.
13
Department of Education and Training, Tohoku University School of Medicine, Sendai, Japan.
14
Center for Individualized Medicine, Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
15
Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA.
16
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
17
Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA.
18
Division of Medical Genetics, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy.
19
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
20
Department of Medical Genetics, Osaka Women's and Children's Hospital, Izumi, Japan.
21
Department of Clinical Genetics and GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
22
President, the Research Institute of Personalized Health Sciences, Health Sciences University of Hokkaido, Hokkaido, Japan.

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.

KEYWORDS:

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

Conflict of interest statement

Competing interests: The clinical and molecular genetic experts on Kabuki syndrome who collaborated on this manuscript were all participants of the Kabuki Syndrome Medical Advisory Board organised and sponsored by Takeda in January 2018. Although the meeting was facilitated and organised by Takeda, Takeda did not have any influence on the content of this report.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center