No familial predisposition is present in many patients with aortic isthmus stenosis. In familial cases, there is usually multifactorial inheritance, and autosomal-dominant inheritance is reported more rarely. A family has been described in which aortic isthmus stenoses were inherited over four generations, probably with an autosomal-dominant mode of inheritance, and a high degree of gene penetrance with variable phenotype expression was observed (Beekman and Robinow 1985). Aortic isthmus stenoses often occur in the context of complex syndromes, with Turner syndrome being the one most frequently associated with aortic isthmus stenosis (Table 2.1-9).
There are two hypotheses regarding the cause of aortic isthmus stenosis. In the hemodynamic hypothesis, it is assumed that aortic isthmus stenosis develops on a localized shelf on the posterior wall of the aorta opposite the orifice of the ductus arteriosus. When the ductus arteriosus closes, an obstruction gradually develops in the area of the duct’s orifice (“juxtaductal”), leading to increased resistance (Rudolph et al. 1972). This theory above all explains isthmus stenoses in defects involving left ventricular obstruction such as bicuspid aortic valve, mitral stenosis and subaortic stenosis. However, it does not explain all forms of aortic isthmus stenosis, and in particular does not account for isolated aortic isthmus stenosis with no intracardiac malformations. By contrast, Skoda considered as long ago as 1855 that scattered ductal tissue was responsible for the development of aortic isthmus stenosis. This hypothesis has in the meantime been confirmed by histological analyses (Fig. 2.1-27) (Ho and Anderson 1979). More recent discussion has focused on defective development of cells of the neural crest as the cause of isthmus stenosis (Kappetein et al. 1991).
Table 2.1–8 Malformation associated with congenital aortic isthmus stenosis.
| Malformation | Frequency in aortic isthmus stenosis (%) (Kappetein et al. 1991; Becker et al. 1970; Beekman et al. 1981;Campbell et al. 1980; Clarkson et al. 1983; Hesslein et al. 1981; Lerberg et al. 1982; Liberthson et al.1979; Pennington et al. 1979; Pinzon et al. 1991) |
| Bicuspid aortic valve | 15–65 |
| Aortic valve stenosis or regurgitation | 2–9 |
| Patent ductus arteriosus (PDA) | 10–45 |
| Ventricular septal defect (VSD) | 7–47 |
| Hypoplastic aortic arch* | 22–63 |
| Atrial septal defect (ASD) | 1–18 |
| Mitral valve anomaly (parachute) | 4 |
| Intracranial aneurysms | ~10 |
* The aortic arch is defined as hypoplastic relative to the diameter of the ascending aorta:
Table 2.1–9 Syndromes associated with a risk of congenital aortic isthmus stenosis.
| Turner syndrome |
| Noonan syndrome |
| DiGeorge syndrome |
| Loeys–Dietz syndrome |
| Williams–Beuren syndrome |
| Down syndrome |
| Rubella syndrome |
| Trisomy 18 |
| McCune–Albright syndrome |
| Klippel–Feil syndrome |
| Camptomelic syndrome |
| Shone syndrome |
| Goldenhar syndrome |
| Scimitar syndrome |
| Pierre Robin syndrome |
| Roberts syndrome |
| Type 1 neurofibromatosis |
| Kabuki syndrome |
| Alagille syndrome |
Fig. 2.1–27 In the hemodynamic hypothesis, it is assumed that aortic isthmus stenosis develops on a localized shelf on the posterior wall of the aorta opposite the orifice of the ductus arteriosus. By contrast, Skoda believed that scattered ductal tissue was responsible for the development of aortic isthmus stenosis.
2.1.10.2 Differential diagnosis of aortic isthmus syndrome
Pseudocoarctation refers to elongation and folding of the aorta in the thoracic segment, particularly of the aortic arch and proximal descending thoracic aorta, with no significant pressure gradients. However, there may be an indication for surgery if adjacent organs such as the esophagus are displaced or compressed, or if aneurysmal dilation of the aorta occurs.
Abdominal coarctation, also known as “mid-aortic syndrome” (MAS), is locally circumscribed in two-thirds of the cases. In one-third, however, it may also involve extensive changes. These are usually caused by inflammatory changes such as those seen in Takayasu arteritis or granulomatous vasculitis. The condition is also observed in patients with fibromuscular dysplasia, neurofibromatosis, retroperitoneal fibrosis, extensive atherosclerosis and congenital malformation (Connolly et al. 2002). Typical findings are renal artery stenosis with severe arterial hypertension, while stenoses of the celiac trunk or mesenteric arteries occur less frequently.
2.1.10.3 Clinical findings and course
Children: Two clinical groups are distinguished. Firstly, those with preductal aortic isthmus stenosis, which manifests in the first week of life. In this form of isthmus stenosis, the perfusion of the lower half of the body is dependent on the ductus arteriosus. When the duct closes, acute hypoperfusion of the lower half of the body results. Due to a lack of