Hypoplastic Left Heart Syndrome in Patients With Kabuki Syndrome

Abstract

We read with interest the article by Kung et al. [8] published in a recent issue of Pediatric Cardiology. The investigators reported three patients with Kabuki syndrome and hypoplastic left heart who were diagnosed at a single institution. An additional patient with Kabuki syndrome and hypoplastic left heart, associated with partial anomalous pulmonary venous drainage, was previously described by Shahdadpuri et al. 2008 [14]. The association of cardiac left-sided obstructive lesions with a subset of patients, prevalently male, with Kabuki syndrome has been previously described by our group [4]. Cardiac defects in these cases consisted particularly of coarctation of the aorta, with multiple left-sided obstructions similar to those observed in the spectrum of Shone complex [15]. The prevalence of left-sided obstruction lesions in our previous series (including 35 patients with congenital heart defect among a total of 60 patients with Kabuki syndrome diagnosed between January 1992 and February 2000) was 29%, and a similar percentage was found among reports from the literature at that time (33%). A review by Armstrong et al. 2005 [1, 9] confirmed that the prevalence of left-sided obstructions in Kabuki syndrome (31%) is significantly (P \ 0.001) higher compared with that in the general population (14%) [6]. Review of our present series, which includes 121 patients with Kabuki syndrome diagnosed between January 1992 and May 2010, showed congenital heart defect in 71 of 121 (59%) patients and left-sided obstructions in 27 of 71 (38%) patients with congenital heart defect. Hypoplastic left heart syndrome was diagnosed in 5 patients, corresponding to 4.1% (5 of 121) of total patients, 7% (5 of 71) of patients with congenital heart defect, and 19% (5 of 27) of patients with left-sided obstructions. Three patients with hypoplastic left heart were male, and two were female. Clinical characteristics of these patients are listed in Table 1. All had normal standard chromosome analysis. These patients underwent an initial clinical examination in the first days of life. The diagnosis of Kabuki syndrome was made at time of first observation in thee patients (patients no. 1 through 3), whereas for two additional patients (patients no. 4 and 5), Kabuki syndrome was suspected at 4 years of age when specific facial anomalies, mental retardation, brachydactyly of hands with persistent finger pads, and ear anomalies were noted. The syndrome more frequently considered in differential diagnosis when evaluating female newborns with hypoplastic left heart is Turner syndrome, considering that facial and cardiac anomalies partially overlap [2, 4, 13]. Specific clinical features suggestive for Kabuki syndrome in these cases included cleft palate, ears anomalies (preauricular pits, deafness), joint hypermobility, full areolae, delayed developmental milestones, and more pronounced feeding difficulties. It is noticeable that the percentage of female patients with hypoplastic left heart syndrome and Kabuki syndrome in the present series (2 of 5 [40%]) is relatively higher compared with that found among patients with other left-sided obstructions, such as aortic coarctation (4 of 15 [27%]). The genetic basis of hypoplastic left heart syndrome is currently unknown. Specific syndromes known to be M. C. Digilio (&) A. Baban B. Dallapiccola Medical Genetics and Pediatric Cardiology, Bambino Gesu Pediatric Hospital, Rome, Italy e-mail: maria.digilio@opbg.net