Case series of right aortic arch: prenatal diagnostic approach Serie de casos de arco aórtico derecho: aproximación diagnóstica prenatal

The right aortic arch is a product of abnormal involution of the embryonic vascular arches. In recent years, fetal diagnosis has become more frequent with the use of routine ultrasonography of the heart and great vessels. The finding of a right aortic arch involves many aspects that may affect the prognosis of the fetus; therefore, the exhaustive study must be systematized. Below, we present a series of six cases of prenatal diagnosis and suggest an evaluation algorithm.


IntroductIon
The normal formation of the aortic arch occurs during the embryonic period from the involution of the pharyngeal vascular arches in a complex process. The third arch forms the carotid arteries, the fourth arch the aortic arch itself and the sixth the ductus arteriosus with the pulmonary arteries. The laterality of the aortic arch is caused by the involution of the right arch. Alterations of the aortic arch involve not only the laterality of the arch, but also the persistence of both arches, the interruption of the arch and abnormalities in the birth of the cephalic vessels (1) . Right aortic arch (RAA) has an incidence of approximately 0.1% of gestations. Fetal diagnosis in recent years has become more frequent with the use of the ultrasonographic approach to the heart and great vessels recommended by the International Society of Ultrasonography in Obstetrics and Gynecology (ISUOG), which assesses crosslinking of the great vessels in the superior mediastinum (2,3) .
The finding of an RAA involves many aspects that may affect the prognosis of gestation; therefore, the exhaustive examination should be systematized. Below, we present a series of prenatal diagnostic cases and suggest an evaluation algorithm.

case serIes report
The series of cases occurred over a period of 4 years. The main patient data are abstracted in Table 1. For the diagnosis, fetal echocardiography with Doppler was performed in all cases, for evidence of the shape of the vascular ring of the right aortic arch and to search for aberrant left subclavian artery (ALSA) or Kommerell's diverticulum (Figures 1 to 5). In the most recent cases, STIC (spatio-temporal image correlation) technology was used for three-dimensional reconstruction of the aortic arch, Kommerell's diverticulum and aberrant left subclavian artery (Figures 3, 4 and 5).

dIscussIon
RAA is diagnosed by prenatal ultrasound in the three-vessel and tracheal section of the heart examination, the normal finding being that the aorta and ductus arteriosus are on the left side of the trachea. On the other hand, the right aortic arch will be on the right side of the trachea, closer to the superior vena cava (2) . It is necessary to determine the side on which the ductus arteriosus runs, since if it is on the right side, the possibility of a vascular ring is minimal, but  of the vessels will be seen ( Figures 1C, 2A, 2B, 3C, 5A). In our series, we found the ductal arch on the left side in all cases studied, associating in all of them the characteristic U-shape of the vascular ring (1) . Likewise, it is necessary to ex-  tend the evaluation with the visualization of the origin of the aortic vessels (the use of Doppler is absolutely necessary), focusing on the search in ALSA (artery that arises from the descending    in cases of RAA or the aberrant left subclavian artery has its origin) (1) (Figures 4C, 5B and 5C). Of the 6 cases presented in this series, in 4 of them it was possible to visualize ALSA associated with Kommerell's diverticulum at its origin.
There are up to 5 varieties in the birth of the vessels of an RAA, but two are the most important in the fetus (1) . The most frequent form is characterized by aberrant left subclavian artery (ALSA) arising from Kommerell's diverticulum, with little association with added cardiac malformations, but which can form symptomatic vascular ring ( Figures 4B, 4C, 5B and C). The second form in frequency is the variant with mirror aortic vessels, with a high association to cardiac malformations and little risk of forming a vascular ring (1,4) . The evaluation of both varieties requires great experience of the examiner. Threedimensional vascular reconstruction could also be used for a more detailed analysis, by means of spatio-temporal image correlation (STIC). We recommend reviewing the algorithm published by Wang for further evaluation (5) . Vigneswaran (6) , in an extensive series of cases of isolated RAA (138), reports 70 fetuses with a variant with mirror aortic vessels and 5 with ALSA. In contrast, the data published by Campanale (7) (37 fetuses) show 56% of ALSA and only 10% of mirror aortic vessels.
The cardiac malformations frequently associated with RAA are conotruncal malformations, including tetralogy of Fallot (especially the variant with pulmonary valve agenesis); others are septal defects and isomerisms (4,(8)(9)(10)(11) . The series of 98 cases published by Miranda (9) graphs these data, finding tetralogy of Fallot in 50% of cases, septal defects in 11% and 8.5% of isomerism. Likewise, these findings are consistent with the 50 cases reported by Zidere (7) . In our series, 2 of the cases showed associated cardiac anomalies, in both cases with isomerism ( Table 1).
The prevalence of extracardiac malformations associated with RAA is variable; it is reported between 14.6% and 31% (9,12) . It is necessary to point out that the association with extracardiac malformations increases the risk of 22q11.2 deletion (11) . The extracardiac features that should be looked for when 22q11.2 is suspected are facial dysmorphisms, renal malformations and thymus hypoplasia (13) . For prenatal evaluation of thymus hypoplasia we recommend the Chaoui technique (thymus/thorax ratio) (14) . In accordance with this prevalence, in two cases (40%) extracardiac anomalies were evidenced, with the first case presenting bilateral renal agenesis, sacral myelomeningocele and allobar holoprosencephaly; while in the second case bilateral facial clefting, unilateral microphthalmia and severe ventriculomegaly were found. In addition, thymus hypoplasia was found in two cases, but genetic testing was not performed ( Table 1).
The association of RAA with chromosomopathies is 9% overall; however, if only cases without heart disease or extracardiac malformation are considered, it decreases to 4.6% (12) . The study of chromosome 22q11.2 deletion is recommended if RAA is associated with other cardiopathies (especially conotruncal: tetralogy of Fallot, truncus arteriosus, coarctation of the aorta), when finding an absent/hypoplastic thymus and/or extracardiac malformations (facial, soft palate, renal) (15) . Thus, Zidere, in a series of 75 cases with high association to cardiopathies, found a 24% prevalence of 22q11.2 deletion (8) . The case is different when finding an 'isolated' RAA, where the probability is 4%-8.5%, as shown in multiple series and meta-analyses (4,6,12,16) .
The long-term prognosis in cases without other malformations is determined by the symptomatology of the vascular ring, which is formed by the right aortic arch, the left aberrant left subclavian artery, and the left descending aorta with the left ductus arteriosus, which finally joins the left subclavian artery with the left pulmonary artery. Although most children affected by vascular rings are asymptomatic, the incidence of respiratory or esophageal symptoms in the first years of life in children with prenatal diagnosis of RAA varies between 13% and 25% (4,6,12,17) . Of the 6 cases reported in our series, one of them ended in fetal death, two had an early neonatal death, and the other three were followed up postnatally between 3 and 12 months of life, being asymptomatic until the date of this publication (Table 1).
In conclusion, when a right aortic arch is found, it is necessary to establish a detailed study and sequential study, in order to determine the pertinence of the genetic diagnostic tests, as we propose in the evaluation algorithm ( Figure 6); this will allow us to provide adequate counseling to the mother on prognosis and follow-up at birth.