Introduction
Kabuki syndrome, also known as Kabuki make-up syndrome, is a rare genetic disorder characterised by distinctive facial features, growth retardation, intellectual disability, and skeletal abnormalities. First described in Japan in 1981, the syndrome has now been identified worldwide, with an estimated prevalence of 1 in 32,000 births. It is primarily caused by mutations in the KMT2D gene and, less frequently, in the KDM6A gene.
Congenital heart disease is observed in 28–80% of patients with Kabuki syndrome. Among the congenital heart defects, mitral valve prolapse and mitral regurgitation are observed with a frequency of 5–10%, whereas mitral stenosis is very rarely detected with a frequency of 1–2%. Reference Alpat, Alma and Yılmaz1 The aim of this case report is to discuss the clinical presentation, diagnostic process, and therapeutic strategies used in the management of a patient with this rare combination of Kabuki syndrome and mitral stenosis.
Case presentation
A six-year-old male patient was evaluated for hypotonia during the neonatal period and was diagnosed with Kabuki syndrome by genetic testing following a muscle biopsy. The patient was subsequently followed by the paediatric genetics and paediatric neurology departments. During the same period, an echocardiogram performed for further evaluation revealed a bicuspid aortic valve and a parachute mitral valve. The patient was followed regularly by the paediatric cardiology clinic. Due to increasing valvular and supravalvular mitral stenosis observed during follow-up, the patient was referred to our department.
Echocardiographic evaluation of the patient revealed a “parachute” appearance of the mitral valve, accompanied by mitral stenosis (mitral annulus: 20 mm with a z-score: −1.87). The degree of mitral stenosis was measured using PW Doppler, with a peak gradient of 11 mmHg and a mean gradient of 5 mmHg. Also, the mitral leaflet separation (MLS): 10 mm, effective orifice area (EOA): 0.67 cm2/m2. No mitral regurgitation was observed. However, the right heart chambers were markedly dilated. Additionally, during the suprasternal examination, a notable ascending vertical flow was observed, prompting a request for cardiac CT imaging (Figure 1a,b). Cardiac CT showed abnormal drainage from the left upper pulmonary vein into the superior vena cava via a vertical vein and dual drainage into the left atrium. In addition, a hemiazygos vein was observed draining into the junction of the superior vena cava and the vertical vein (Figure 1c,d). Subsequently, cardiac MRI was requested to assess cardiac volume and functions, as well as the condition of the mitral valve and left atrium. Cardiac MRI showed mitral stenosis, and the mitral area was calculated as 1.1 cm2 by planimetric measurement. Both ventricular functions were normal, and the Qp/Qs ratio was 2.02. However, left atrial enlargement (left atrial volume index [LAVI]: 60.8 ml/m2) was disproportionate to the mitral stenosis gradient measured by echocardiography. Despite the presence of a single anomalous pulmonary vein drainage, the right ventricle was significantly dilated. All these findings were discussed in the Paediatric Cardiology Council. It was concluded that despite significant mitral stenosis, the presence of anomalous pulmonary venous drainage and the hemiazygos vein acting as a pressure relief valve made Doppler measurements insufficient for evaluation.
(a) Dilatation in the right heart chambers and mitral stenosis. (b) Vertical venous flow observed at the level of the aortic arch. (c) Drainage of the left upper pulmonary vein into the superior vena cava with the vertical vein in cardiac 3D CT imaging, in the coronal section. (d) Abnormal continuity of the hemiazygos vein with the left upper pulmonary vein in cardiac 3D CT imaging, in the lateral section.
After evaluation of the patient’s current findings and investigations, surgery for intramitral ring resection, mitral commissurotomy, vertical vein ligation, and atrial septectomy was performed. Postoperative echocardiography showed mild mitral regurgitation without stenosis. No arrhythmia was observed on Holter monitoring. The patient was successfully discharged on postoperative day 7 and scheduled for outpatient follow-up.
Discussion
Kabuki syndrome is a genetic disorder characterizsed by prominent facial anomalies, mental retardation, congenital heart disease, and skeletal malformations. The association of Kabuki syndrome with congenital heart disease has been reported in the literature with a prevalence ranging from 28 to 83%. Reference Digilio, Marino and Toscano2–Reference Ohdo, Madokoro and Sonoda6 The most associated congenital heart defects include coarctation of the aorta, atrial septal defect, and ventricular septal defect. Reference Digilio, Marino and Toscano2,Reference Niikawa, Kuroki and Kajii5 However, mitral stenosis and its surgical management in association with this syndrome have been infrequently described. Reference Alpat, Alma and Yılmaz1 The coexistence of mitral stenosis and a levoatriocardinal vein has been rarely reported in the literature. Reference Raju, Sharma and Chandrashekhara7,Reference Rauch, Grosse-Wortmann and Jones8 This coexistence complicates the clinical picture. The dual drainage of the left upper pulmonary vein and the presence of a hemiazygos vein acting as a pressure relief valve are unique findings that have not been previously documented. These anatomical variations may obscure the haemodynamic assessment typically used to measure the severity of mitral stenosis, leading to a potential underestimation of the impact of the disease.
In our case, the significant dilatation of the left atrium, despite a low Doppler gradient, indicated that the mitral stenosis was more severe than initially appeared. This discrepancy highlights the importance of considering anatomical abnormalities when assessing cardiac function in patients with Kabuki syndrome. The decision to proceed with surgery was ultimately guided by a comprehensive understanding of the patient’s unique anatomy, rather than relying solely on standard diagnostic metrics.
Surgical intervention included intramitral ring resection, mitral commissurotomy, vertical vein ligation, and atrial septectomy. Atrial septectomy was performed to decompress the markedly dilated left atrium and to optimise pulmonary venous return, particularly in the context of dual drainage and a haemodynamically significant left atrial volume overload not fully reflected by Doppler measurements. Additionally, atrial septectomy was considered beneficial for minimising postoperative complications such as pulmonary venous congestion, pulmonary oedema, and atrial arrhythmias by providing effective left atrial decompression and improving intracardiac flow dynamics.
Alternative surgical approaches described in the literature include mitral valve replacement in cases where anatomical distortion renders reconstruction insufficient. Reference Krzystolik-Ladzińska, Wites, Wites, Gołba, Mazurek and Szydłowski9 In patients with anomalous pulmonary venous return, rerouting the vertical vein to the left atrium instead of ligation has been proposed, although this may not be feasible in cases with complex venous anatomy. Reference Di Pasquale, Jäger, Cesnjevar and Dave10 Additionally, transcatheter occlusion of a residual patent vertical vein in a staged fashion has emerged as a minimally invasive alternative in cases where surgical rerouting is not initially performed. Reference Gumustas, Donmez, Aykan, Demircin and Karagoz11 These options should be considered on a case-by-case basis, depending on the patient’s unique anatomical and physiological features.
It should therefore be recognised that patients diagnosed with Kabuki syndrome may be presented with a variety of congenital heart diseases, requiring a detailed paediatric cardiac assessment. Clinicians should be aware of the potential for complex vascular anomalies and their impact on cardiac function and ensure that management strategies are tailored to the individual patient’s anatomical and physiological characteristics.
Financial support
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Competing interests
None.
Ethical standards
All interventions conducted in this case adhered to the ethical principles outlined by the institutional and national research ethics committees, in full compliance with the Declaration of Helsinki (1975) and its subsequent revisions or equivalent ethical guidelines.
Informed consent
Informed consent was obtained from the patient’s parents.
