Rare double orifice mitral valve malformation associated with bicuspid aortic valve in Turner syndrome: diagnosed by a series of novel three-dimensional echocardiography and literature review

The double orifice mitral valve (DOMV) is considered a rare congenital heart malformation due to the abnormal embryonic development of the endocardial cushion and myocardium, characterized by a two-channel atrioventricular valve in the left ventricle and accounting for about 0.05% of all congenital heart diseases [1, 2]. The two orifices of the mitral valve (MV) can be symmetrical or asymmetrical, isolated or exist with other cardiac malformations, and can be divided into complete bride type, incomplete bridge type, or hole type [3, 4]. A bicuspid aortic valve (BAV) is relatively common and is characterized by the abnormal fusion of two leaflets of the aortic valve (AV) during development, resulting in a two leaflet valve instead of the normal tricuspid AV [5]. Patients with both DOMV and BAV are rare [6].

Turner syndrome (TS), known as congenital chromosomal disorder, is caused by the partial or complete deficiency of the X chromosome and is reported to have a higher incidence of congenital heart diseases, of which AV malformation is one of the most common changes [7, 8]. Reported mitral malformations in TS are MV prolapse, myxomatous degeneration, parachute-like MV, cleft, and accessory leaflet [9‐12]. To our knowledge, the occurrence of DOMV in TS has not been reported.

The two-dimensional echocardiography (2DE) is the most common and important method for detecting congenital heart valvular disease [13]. Meanwhile, the role of real-time three-dimensional echocardiography (RT-3DE) in the diagnosis and evaluation of congenital heart diseases has been receiving more attention due to its ability to show the overall spatial structure of the heart [14]. Several novel 3DE imaging technologies have been developed by Philips Medical System recently. TrueVue technology, which came out in 2019, is a new, high-resolution 3D echocardiographic imaging mode that can clearly display the subtle structure of the heart, which makes the ultrasound image more closely resemble the real anatomical pathology [15]. The TrueVue Glass, released globally in 2020, displays the myocardial tissue outside the heart cavity in a transparent mode, focusing on the cardiac cavity filled with blood flow, and can display the thin and translucent valves, which provides both a practical value and technological sense during the diagnosis and evaluation of heart diseases [16].

Here, we report a case with TS and congenital cardiac valvular malformations with DOMV and BAV, wherein we applied these advanced 3DE imaging technologies, which played an important role by providing images and diagnostic information that were previously unavailable.

A 5-year-old girl presented to our hospital with a complaint of short stature and mild backache. She was found to have vitamin D deficiency, spina bifida, and small pituitary volume. Her peripheral blood chromosome result indicated “45, X,” consistent with TS.

To rule out developmental delay due to heart disease or cardiac abnormalities associated with TS, the transthoracic Echocardiogram (TTE) was performed using Philips EPIQ CVx cardiovascular specific ultrasonic diagnostic equipment (Philips Medical System, Andover, MA, USA). The 2DE scan application was conducted via a S9-2 (2–9 MHz) probe. The X5-1 (1–5 MHz) probe was used for the 3DE examination. As diagnoses of both DOMV and BAV were suspected, the MV apparatus and AV-related structures were examined by 3D-TTE for further morphological and functional evaluation. On the basis of traditional 3D imaging, we launched the new TrueVue imaging mode. In TouchVue, in addition to being able to directly zoom and rotate the image with two fingers on the touch screen, more importantly, a single finger click on the target structure can display and move the position and depth of a virtual light source. Based on the TrueVue image, we further applied the Glass mode to obtain a transparent rendering effect. The short-axis view at the level of the MV via above-mentioned four techniques demonstrated that there were asymmetric double left atrioventricular orifices divided by a complete fibrous bridge, of which the anterolateral orifice was larger (Fig. 1). The total area of the two mitral orifices was about 2.17 cm². At the level of the papillary muscle, four papillary muscles were revealed by 2D-TTE, traditional 3D-TTE, and TrueVue images, but were transparent and only the borders were revealed in the TrueVue Glass image (Fig. 2). The spatial relationship demonstrated that the two orifices were connected by their respective chordae tendineae, separating the two papillary muscles of the same side (Fig. 3). Color Doppler was superimposed, demonstrating two jets through the respective channels of the two orifices (Fig. 4). The real-time dynamic TrueVue Glass image can visualize the 3D blood flow through the thin and transparent valve (Additional file 1: Video 1). In this patient with MV malformation, we initiated the “dual volume” mode so that we could simultaneously observe two orifices on the left atrial view, four papillary muscles on the left ventricle view and the flow in two opposite directions. (Additional file 2: Video 2). There was a slight increase in the forward blood flow velocity of the left atrioventricular valve orifices, the velocity in the early diastole was about 1.2 m/s, and in the late diastole was about 0.7 m/s. In addition, the short-axis view of the heart base revealed a BAV, with two leaflets in the left anterior and right posterior directions. We simultaneously compared the two-dimensional, traditional 3D, and new 3D TrueVue combined with the light and Glass mode imaging. Via TrueVue Glass imaging, when the light source was placed behind the valves, we observed a straight-line AV closure shape; the emergence of the coronary arteries and the spatial character of the aortic arch were also displayed simultaneously (Fig. 5). There was no aortic stenosis (peak systolic velocity is 1.3 m/s) or regurgitation, and the aortic arch descended to the left normally. Trivial mitral regurgitation was observed, but no other associated congenital cardiac abnormalities were detected. Surgical intervention was not performed for the time being because there was no significant regurgitation or stenosis. The results of the echocardiographic follow-up after three months, half a year, and 1 year showed that there was no obvious stenosis or insufficiency of the valves.

We further reviewed 24 patients with both DOMV and BAV in 16 references from 1988 to 2020 (Table 1). These patients ranged in age from one month to 67 years old (25.55 ± 19.95), including 12 (50.0%) adults, 10 (41.7%) children or adolescents, and 2 (8.3%) patients whose ages were not described. Overall, 15 (62.5%) were male, 7 (29.2%) were female, and 2 (8.3%) were of undescribed gender. Except for 1 (4.2%) case in which the specific DOMV type was unknown, all the other cases were of complete bridge type, and in patients with relevant record information, there was an even distribution of symmetrical and asymmetrical orifices. As for the dysfunction of the MV and AV, mitral regurgitation was the most common, present in 10 (41.7%) patients, aortic stenosis in 8 (33.3%), mitral stenosis in 7 (29.2%), and aortic regurgitation in 4 (16.7%). Chordae tendineae was noted in 12 (50.0%) patients: the chordae attached to each orifice in 5 (20.8%); accessory septal attachment in 2 (8.3%); parachute chordal attachments in 2 (8.3%); and attachment to the anterior wall, chordal ring, non-elongation, and one chorda attachment to the bridging structure were seen in 1 (4.2%) case each. Papillary muscles were mentioned in 14 cases (58.3%). They were normal in 6 (25.0%) and fused in 3 (12.5%); the morphology was abnormally displaced and unequal in a normal number of papillary muscles in 2 (8.3%), and four or more papillary muscles were noted in 3 (12.5%). The most complicated malformation was coarctation of the aorta (n = 11, 45.8%). All patients underwent echocardiography, and among them, 10 (41.7%) underwent transesophageal echocardiography (TEE) and 9 (37.5%) underwent 3DE. Of the 13 (54.2%) patients with operation-related information, 8 (33.3%) underwent operations, although some of them underwent an operation to correct the aortic constriction rather than repair or replace the deformed valve. None of the reported cases involved a genetic syndrome except our case.

An invasive TEE is not usually necessary for diagnosis due to the excellent acoustic window. Clear display of children’s valves via traditional 2DE and 3DE has certain difficulties due to their thinness, easily leading to misdiagnosis by inexperienced sonographers [17]. TrueVue is a novel 3D rendering mode with high resolution [18]. By changing the position and depth of the light source, realistic light and shadow effects can be obtained while illuminating the target structure, simulating it, including the texture of the double orifices and the sub-valvular apparatus, into photorealistic 3D images. TouchVue provides an operating platform that can effectively improve work efficiency. The TrueVue Glass imaging shields the myocardial tissue, specifically the blood-containing heart chambers and blood vessels, depicting thin BAV in its entirety. Especially when the light source was strategically placed behind the valve, light transmitted from the opening valve clearly revealed that the “fish mouth” bicuspid valve was completely different from the “inverted triangle” of the three-leaflet AV. Even the contour of the aortic arch and right coronary artery lumens were displayed clearly in TrueVue Glass images when viewing the short axis of the AV, which cannot be seen in traditional 3D or TrueVue images. Color on all three rendering modes showed two exact jets from the left atrium side, confirming the diagnosis of 2D-TTE. The main advantages and disadvantages of these imaging methods developed by Philips company in the diagnosis of this case are summarized in Table 2. Another limitation of these new series of 3D ultrasound techniques is that they require an uncomplicated training of methods and techniques before they can be used effectively. To our knowledge, this is the first case diagnosed with DOMV and BAV using the above series of novel 3DE techniques.

Lesions of the MV apparatus sometimes occur simultaneously and do not involve just the leaflets [19]. In this case, DOMV was first detected, and then the abnormal number of papillary muscles was noted. BAV can be associated with specific syndromes, like Marfan, William Beuren, Andersen, Bosley-Salih-Alorainy, Athabascan Brainstem Dysgenesis, Turner, and Vascular Ehlers-Danlos syndromes [5]. Furthermore, three DOMV cases with hereditary syndromes (Ellis-van Creveld, Sotos, and Holt–Oram syndrome) have been reported [20‐22]. In addition, the fact that BAV occurs more frequently in males and in patients with TS suggests a potential X-linked inheritance [7, 23]. Fernandez Gasso L presented an idea that multivalvular disease may be genetic [24]. Based on these findings, our case may be a hint that multivalvular disease is associated with the X chromosome.

The patient is not currently undergoing surgery because there is no significant valve regurgitation or stenosis. However, with aging, valve elasticity decreases, which will aggravate valve dysfunction [25]; therefore, long-term follow-up of this patient is essential.

In conclusion, this case extended the possible complex lesions in TS and endorses 3D transillumination rendering techniques in detecting valvular malformations.