Premium
Congenital heart defects in molecularly proven Kabuki syndrome patients
Author(s) -
Digilio Maria Cristina,
Gnazzo Maria,
Lepri Francesca,
Dentici Maria Lisa,
Pisaneschi Elisa,
Baban Anwar,
Passarelli Chiara,
Capolino Rossella,
Angioni Adriano,
Novelli Antonio,
Marino Bruno,
Dallapiccola Bruno
Publication year - 2017
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.38417
Subject(s) - kabuki syndrome , medicine , bicuspid aortic valve , cardiology , hypoplastic left heart syndrome , foramen secundum , aortic arch , heart defect , heart disease , aortic valve , pediatrics , aorta , patent foramen ovale , migraine
The prevalence of congenital heart defects (CHD) in Kabuki syndrome ranges from 28% to 80%. Between January 2012 and December 2015, 28 patients had a molecularly proven diagnosis of Kabuki syndrome. Pathogenic variants in KMT2D (MLL2) were detected in 27 patients, and in KDM6A gene in one. CHD was diagnosed in 19/27 (70%) patients with KMT2D (MLL2) variant, while the single patient with KDM6A change had a normal heart. The anatomic types among patients with CHD included aortic coarctation (4/19 = 21%) alone or associated with an additional CHD, bicuspid aortic valve (4/19 = 21%) alone or associated with an additional CHD, perimembranous subaortic ventricular septal defect (3/19 = 16%), atrial septal defect ostium secundum type (3/19 = 16%), conotruncal heart defects (3/19 = 16%). Additional CHDs diagnosed in single patients included aortic dilatation with mitral anomaly and hypoplastic left heart syndrome. We also reviewed CHDs in patients with a molecular diagnosis of Kabuki syndrome reported in the literature. In conclusion, a CHD is detected in 70% of patients with KMT2D (MLL2) pathogenic variants, most commonly left‐sided obstructive lesions, including multiple left‐sided obstructions similar to those observed in the spectrum of the Shone complex, and septal defects. Clinical management of Kabuki syndrome should include echocardiogram at the time of diagnosis, with particular attention to left‐sided obstructive lesions and mitral anomalies, and annual monitoring for aortic arch dilatation.