A large proportion of patients with congenital heart disease (CHD), in particular those with relevant systemic-to-pulmonary shunts, will develop pulmonary arterial hypertension (PAH) if left untreated. Persistent exposure of the pulmonary vasculature to increased blood flow, as well as increased pressure, may result in pulmonary obstructive arteriopathy, which leads to increased pulmonary vascular resistance that, if it approaches or exceeds systemic resistance, will result in shunt reversal. Eisenmenger's syndrome, the most advanced form of PAH associated with CHD, is defined as CHD with an initial large systemic-to-pulmonary shunt that induces severe pulmonary vascular disease and PAH, with resultant reversal of the shunt and central cyanosis. The histopathological and pathobiological changes seen in patients with PAH associated with congenital systemic-to-pulmonary shunts, such as endothelial dysfunction of the pulmonary vasculature, are considered similar to those observed in idiopathic or other associated forms of PAH. A pathological and pathophysiological classification of CHD with systemic-to-pulmonary shunt leading to PAH has been developed that includes specific characteristics, such as the type, dimensions and direction of the shunt, extracardiac abnormalities and repair status. A clinically oriented classification has also been proposed. The prevalence of PAH associated with congenital systemic-to-pulmonary shunts in Western countries has been estimated to range between 1.6 and 12.5 cases per million adults, with 25-50% of this population affected by Eisenmenger's syndrome. Clinically, Eisenmenger's syndrome presents with multiple organ involvement, with progressive deterioration of function over time. The signs and symptoms of Eisenmenger's syndrome in the advanced stages include central cyanosis, dyspnoea, fatigue, haemoptysis, syncope and right-sided heart failure. Survival of patients with Eisenmenger's syndrome is clearly less than that of the general population, but appears to be better than that of patients with idiopathic PAH in a comparable functional class. The treatment strategy for patients with PAH associated with congenital systemic-to-pulmonary shunts and, in particular, those with Eisenmenger's syndrome is based mainly on clinical experience rather than being evidence based. General measures include recommendations for physical activity, pregnancy, infections, air travel, exposure to high altitudes and elective surgery, and that psychological assistance be provided as necessary. Phlebotomies are required only when hyperviscosity of the blood is evident, usually when the haematocrit is >65%. The use of supplemental oxygen therapy is controversial and it should be used only in patients in whom it produces a consistent increase in arterial oxygen saturation. Oral anticoagulant treatment with warfarin can be initiated in patients with pulmonary artery thrombosis and absent, or only mild, haemoptysis. The following three classes of drugs targeting the correction of abnormalities in endotheli...

Recently, mutations in the SMAD3 gene were found to cause a new autosomal dominant aneurysm condition similar to Loeys-Dietz syndrome (LDS), mostly with osteoarthritis, called aneurysms-osteoarthritis syndrome (AOS). Our 3-year-old propositus underwent correction of an inguinal hernia at 3 months and substitution of the ascending aorta for pathologic dilation at 12 months of age. Family history reveals aortic dilation in his mother at 30 years, death due to aortic dissection of an 18-year-old maternal aunt, surgical replacement of the ascending aorta because of aneurysm in a maternal uncle at 19 years, postpartum death of the maternal grandmother at 24 years and surgical intervention because of thoracic aortic aneurysm in a brother of the propositus' grandmother at 54 years. The affected individuals present with several other signs of connective tissue disease, but the two adult patients evaluated revealed no radiologic evidence of osteoarthritis. Molecular testing of the TGFBR1 and TGFBR2 genes, involved in LDS, resulted negative, but analysis of SMAD3 disclosed the novel heterozygous loss-of-function mutation c.1170_1179del (p.Ser391AlafsX7) in exon 9 in all affected family members, confirming the diagnosis of AOS. SMAD3 mutations should be considered in patients of all ages with LDS-like phenotypes and negative TGFBR1/2 molecular tests, especially in the presence of aortic root or ascending aortic aneurysms, even though signs of early onset osteoarthritis are absent.

Early rapid maxillary expansion and mandibular advancement using Propulsor Universal Light appliance significantly improved airway patency of Marfan's syndrome children and are strongly encouraged as a routine treatment for both correction of class II malocclusions and prevention of obstructive sleep apnea.