RT Journal Article
SR Electronic
T1 Kabuki syndrome: international consensus diagnostic criteria
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 89
OP 95
DO 10.1136/jmedgenet-2018-105625
VO 56
IS 2
A1 Margaret P Adam
A1 Siddharth Banka
A1 Hans T Bjornsson
A1 Olaf Bodamer
A1 Albert E Chudley
A1 Jaqueline Harris
A1 Hiroshi Kawame
A1 Brendan C Lanpher
A1 Andrew W Lindsley
A1 Giuseppe Merla
A1 Noriko Miyake
A1 Nobuhiko Okamoto
A1 Constanze T Stumpel
A1 Norio Niikawa
A1 ,
YR 2019
UL http://jmg.bmj.com/content/56/2/89.abstract
AB 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.