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CASE REPORT
Year : 2022 | Volume
: 11
| Issue : 4 | Page : 111-114
A rare case of williams–Beuren syndrome with presence of fibrocalcific supravalvular aortic stenosis and supravalvular pulmonary stenosis: Genetic disorder that bites the gene and bites the heart
Debasish Das, Anindya Banerjee, Abhinav Kumar, Shashikant Singh, Tutan Das, Manaranjan Dixit
Department of Cardiology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
Correspondence Address:
Dr. Debasish Das
Department of Cardiology, All India Institute of Medical Sciences, Bhubaneswar - 751 019, Odisha
India
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/rcm.rcm_9_22
We report an extremely rare case of Williams–Beuren (WB) syndrome in a 10-year-old boy with supravalvular aortic stenosis (SVAS) secondary to a large fibrocalcific eccentric shelf in the ascending aorta with fibrocalcific severe supravalvular pulmonary stenosis, which has not yet been described in the literature. Although the presence of peripheral pulmonary stenosis is well described in Williams syndrome (WS), our case is the unique and first to demonstrate fibrocalcific severe supravalvular pulmonary stenosis in WS without the presence of peripheral pulmonary artery stenosis. Although regarded as a strong genetic insult with 27 gene deletions (almost like biting the gene), it has also bitten the heart in this index child and left a large chunk of supravalvular fibrocalcific mass in the ascending aorta causing SVAS.
Keywords: Gene, supravalvular aortic stenosis, supravalvular pulmonary stenosis, Williams syndrome
Williams syndrome (WS) is encountered in one in 20,000 live births. WS was first described in 1961 in New Zealand by John C. P. Williams. It is regarded as one of the mutilating genetic disorders, in which about 27 genes from the long arm of one of the two chromosomes 7s get deleted randomly either in the ovum or the sperm. Despite so many genetic deletions, the paradoxical aspect of WS is that those people have outgoing personalities, and they remain quite happy. Elfin facies, which is the characteristic in this anomaly, includes a triad of broad forehead, short nose, and underdeveloped chin. Children with Willaim Syndrome are able to speak fluently but they are poor in drawing. “If a child is drawing a beautiful art, it cannot be of WS.” Supravalvular aortic stenosis (SVAS) with hourglass deformity of the ascending aorta although described as unique to this anomaly,[1] our case is unique and the first to demonstrate a large chunk of a fibrocalcific eccentric shelf in ascending aorta causing SVAS. Although peripheral pulmonary stenosis is well described in WS, our case is unique to represent isolated supravalvular pulmonary stenosis without the presence of peripheral pulmonary stenoses in Williams–Beuren (WB) syndrome.
Case ReportCase 1
A 10-year-old boy presented to the cardiology outpatient department with effort dyspnea Ross Class II for the past 5 years without any history of angina, palpitation, syncope, or presyncope. He had no previous heart failure hospitalization. The mother revealed uneventful perinatal history. His motor milestones and speech were normal as per his age, but he was not going to school till now as he was unable to remember and concentrate on his studies. We asked the child to draw an elephant, for which he imagined a lot and eventually he could not draw. On clinical examination, he had elfin facies with a broad forehead, a small stuffy nose, and an underdeveloped chin [Figure 1]. His heart rate was 80 beats/min, and his blood pressure was 100/64 mmHg in the right arm supine position. Cardiac auscultation revealed the presence of aortic stenosis with harsh ejection systolic murmur in the aortic area with severe pulmonary stenosis with loud ejection systolic murmur in the pulmonary area. Chest X-ray did not reveal the presence of poststenotic dilation in either of the ascending aorta or main pulmonary artery suggestive of valvular aortic or pulmonary stenosis. There was no ejection click. Echocardiography (ECG) revealed the presence of biventricular hypertrophy with tall T-waves across precordial leads suggestive of diastolic strain attributable to the presence of gross left ventricular hypertrophy [Figure 2]. ECG revealed the presence of moderate SVAS. Interestingly, there was no characteristic hourglass deformity. SVAS was secondary to the presence of a huge eccentric fibrocalcific shelf in the ascending aorta [Figure 3] with a peak gradient of 58 mmHg and a mean gradient of 27 mmHg [Figure 3]. WS with such a large fibrocalcific shelf in the ascending aorta causing SVAS has not yet been described in the literature. Association of WS with peripheral pulmonary stenosis is well reported; however, interestingly and uniquely, there was severe supravalvular pulmonary stenosis with the presence of a circumferential fibrotic ring in the pulmonary artery [Figure 4] with a peak systolic gradient of 74 mmHg [Figure 4]. A chromosomal study was performed, and the finding of a microdeletion on chromosome 7q11.23 confirmed the diagnosis of Williams syndrome (WS). In view of symptomatic Ross Class II, the child was advised to undergo excision of the large fibrocalcific eccentric shelf in the ascending aorta, followed by bovine patch augmentation of the ascending aorta and polytetrafluoroethylene (PTFE) vascular graft patch in the pulmonary artery to relieve the supravalvular pulmonary stenosis. The child was advised to avoid strenuous outdoor play activity due to moderate SVAS.
Figure 3: Supravalvular large eccentric fibrocalcific shelf with moderate AS. AS: Aortic stenosis
Figure 4: Supravalvular fibrocalcific pulmonary ring with severe supravalvular PS. PS: Pulmonary stenosis Discussion WS is caused by the random deletion of genetic material from a specific region of chromosome 7. The deleted region includes 25–27 genes, and researchers believe that a loss of several of these genes contributes to the characteristic features of this disorder or in toto “WB syndrome bites the heart.” ELN, GTF2I, GTF2IRD1, and LIMK1 are among the genes that are typically deleted in children with WS. Deletion of the ELN gene is associated with connective tissue abnormalities and cardiovascular disease, specifically SVAS characteristics of this disease. Deletion of GTF2I, GTF2IRD1, and LIMK1 genes explains the characteristic difficulties with visual-spatial tasks, unique behavioral characteristics, and cognitive difficulties seen in children with WS. Loss of the GTF2IRD1 gene contributes to the distinctive facial features associated with this condition. Interestingly, deletion of the NCF1 gene on chromosome 7 appears to be a protective factor against developing hypertension in children with WS. Several other genes are also part of the deletion on chromosome 7. Loss of some of these genes appears to be involved in particular signs and symptoms of the condition, and their relationship to the condition is under investigation. We did a genetic study that revealed microdeletion of 7q11.23, which may be contributing to fibrocalcific SVAS with simultaneous supravalvular pulmonary stenosis. There occurs a plethora of genetic deletions in WS, which is still under investigation, and it is also still unclear which particular genetic deletion gives rise to the simultaneous development of supravalvular aortic and pulmonary stenosis; it may be deletion on chromosome 7q11.23 as noted in our case.
The presence of peripheral pulmonary stenosis besides characteristic SVAS has been well described in WS. However, our case is the first literature description of the presence of supravalvular pulmonary stenosis without the presence of branch pulmonary stenosis besides the characteristic SVAS in WS. SVAS and branch pulmonary stenosis in WS occur due to hyperplasia of the elastic lamina of the media;[2] however, interestingly, in our case, a large fibrocalcific eccentric shelf mimicking a large chunk of tissue [Figure 3] was obstructing the supravalvular aorta causing moderate SVAS, and a circumferential fibrocalcific ring was causing supravalvular pulmonary stenosis [Figure 4].
Lee et al. described a case of a male neonate presenting with severe SVAS with peripheral pulmonary stenosis which was surgically corrected at 77 days of life.[2] The index case had delayed presentation as SVAS was moderate. Cases of echogenic mass in the left ventricle[2] have been reported in WS due to fetal endocardial fibroelastosis. Supravalvular fibrocalcific chunk and pulmonary ring in our case may be the remnant of fetal endocardial fibroelastosis. The presence of such a large eccentric fibrocalcific shelf in ascending aorta causing SVAS in WS has not yet been discussed in the literature. Most cases of WS present with severe SVAS in the early neonatal period mandating surgery. Peripheral pulmonary stenosis also presents within 1 and ½ years of life requiring early intervention. The rate of freedom from reoperation or reintervention in SVAS ranges from 83% to 98% at 5 years and from 66% to 83% at 20 years, and the rate of freedom from reoperation or reintervention in peripheral pulmonary stenosis ranges from 32% to 67% at 5 years.[3],[4],[5],[6],[7] Albacker et al. described a case of neonatal SVAS which required urgent repair. WS occurs due to random deletion of up to 27 genes; that is why WS can be told as a genetic disorder that bites the genes. It also bites the heart with severe supravalvular aortic and peripheral stenosis, which mandates early surgery or intervention as peripheral pulmonary stenosis progresses more rapidly in WS with peak deformity by 1 and ½ years of age. That is why collectively WS can be told as a genetic syndrome that bites the gene and bites the heart. Supravalvular stenosis is repaired by cardiac surgeons in a simple manner [Figure 5]. The supravalvular constricted part is incised longitudinally, and a pericardial or bovine pericardial or PTFE graft is sutured to the margins of the incision in a U-shape to widen the aorta or pulmonary artery [Figure 5]. However, our case needed resection, followed by patch augmentation of the fibrotic part. Our case is the first literature description of SVAS in an adolescent secondary to the presence of a large chunk of fibrocalcific tissue. The presence of systemic or suprasystemic right ventricular pressure[8] requires intervention in branch pulmonary stenosis in WB syndrome. The peripheral pulmonary arterial stenosis requires catheter-based intervention before surgery, and patch arterioplasty during SVAS surgery, if catheter intervention fails. The hourglass type of SVAS is more common in WS occurring in ≈75% of children,[9] and the incidence of peripheral pulmonary artery stenosis in WS is 37%–75%.[10] However, in our case, it was an interesting supravalvular large eccentric fibrocalcific shelf with a supravalvular fibrocalcific pulmonary ring. One peculiar thing about WS is that peripheral pulmonary stenosis improves with time.[11] Stamm et al.[12] reported a prevalence of coronary ostial stenosis in 45% of their surgical series of patients with SVAS. Our patient had no coronary ostial stenosis in computed tomography coronary angiogram. Our case is the first literature description of both stenosis in the aorta and pulmonary artery being supravalvular in nature without the presence of peripheral pulmonary stenosis. The elastin haploinsufficiency in WS results in a systemic arteriopathy, sometimes referred to as middle aortic syndrome, which may include discrete coarctation at the aortic isthmus to long-segment narrowing that may involve the aorta from the supravalvular region to the diaphragm and beyond a finding first reported by Beuren et al.[13] Sudden cardiac death also has been reported in WB syndrome as it is sometimes associated with long QT syndrome. Our case is the unique and first description of SVAS due to a large chunk of a fibrocalcific eccentric shelf in the ascending aorta with supravalvular fibrocalcific pulmonary stenosis without the presence of peripheral pulmonary stenosis in WB syndrome. Central pulmonary arteries do not respond well to balloon angioplasty, and the intrapulmonary segments of the pulmonary arteries respond better to balloon dilation, especially when undertaken in a serial manner.[14]
Figure 5: Patch augmentation in supravalvular lesions gives a vertical incision and puts a patch to widen it (applied to the aorta and the pulmonary artery) Conclusion Our case is a unique and interesting description of SVAS in WB syndrome due to the presence of a large eccentric fibrocalcific shelf in ascending aorta with fibrocalcific severe supravalvular pulmonary stenosis without the presence of typical peripheral pulmonary artery stenosis. WS not only bites and deletes the genes but also bites the heart with atypical lesions.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Ethical clearance
Institutional Ethical Committee (IEC) clearance has been obtained.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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