CONOTRUNCAL ANOMALY FACE SYNDROME, INCLUDED
INTERRUPTED AORTIC ARCH, INCLUDED
DORV, INCLUDED
CTHM TRUNCUS ARTERIOSUS COMMUNIS, INCLUDED
PTA, INCLUDED
CAFS, INCLUDED
DOUBLE-OUTLET RIGHT VENTRICLE, INCLUDED
PERSISTENT TRUNCUS ARTERIOSUS, INCLUDED
DORV
In a study of the families of children with cardiac malformations, Pierpont et al. (1988) found that conotruncal malformations carry a higher recurrence risk than other cardiac defects and proposed a monogenic mode of inheritance. Rein et al. ... In a study of the families of children with cardiac malformations, Pierpont et al. (1988) found that conotruncal malformations carry a higher recurrence risk than other cardiac defects and proposed a monogenic mode of inheritance. Rein et al. (1990) described a large kindred in which 2 sibs had truncus arteriosus communis, a first cousin once removed had transposition of the great arteries (TGA; see 608808), and a second cousin had double-outlet right ventricle. Rein and Sheffer (1994) reported 2 additional sibs with conotruncal malformations born into the consanguineous kindred they had previously reported. Le Marec et al. (1989) had raised the question of autosomal recessive inheritance of truncus arteriosus. Typical facial features of conotruncal anomaly face syndrome (CAFS) are ocular hypertelorism (with increased interpupillary distance due to increased separation of the inner canthi), short palpebral fissures, 'bloated' eyelids, a low nasal bridge, a small mouth, and minor ear lobe anomalies. These features are almost always associated with nasal voice (often associated with cleft palate/submucosal cleft palate/bifid uvula) and mild mental retardation (frequently associated with developmental retardation and, occasionally, dwarfism), and often associated with cardiovascular anomalies. The cardiovascular anomalies in patients with the conotruncal anomaly face syndrome mainly consist of cardiac outflow tract defects, such as tetralogy of Fallot (TOF; 187500), pulmonary atresia, double-outlet right ventricle, truncus arteriosus communis, and aortic arch anomalies. Some patients also have hypocalcemia, especially in the neonatal period (sometimes associated with hypoparathyroidism), and thymic aplasia or hypoplasia (Matsuoka et al., 1998). Transposition of the great arteries and double-outlet right ventricle account for 5% and 2%, respectively, of all congenital heart disease (Perry et al., 1993). TGA and DORV are generally classified as conotruncal defects, i.e., defects of the outflow tracts of the heart. The more common form of TGA, dextro-looped TGA (D-TGA), consists of complete inversion of the great vessels, so that the aorta arises from the right ventricle and the pulmonary artery from the left ventricle. In the less common type of TGA, levo-looped TGA (L-TGA), the ventricles are inverted, instead. DORV exhibits marked anatomic variability but is defined by both great vessels arising from the right ventricle (Goldmuntz et al., 2002).
Goldmuntz et al. (2002) presented evidence for a role of CFC1 mutations (605194.0003) in the etiology of TGA and DORV.
Yagi et al. (2003) identified mutations in the TBX1 gene (602054.0001 and 602054.0003) in heterozygous state ... Goldmuntz et al. (2002) presented evidence for a role of CFC1 mutations (605194.0003) in the etiology of TGA and DORV. Yagi et al. (2003) identified mutations in the TBX1 gene (602054.0001 and 602054.0003) in heterozygous state in 3 patients with phenotypes related to the 22q11.2 deletion syndrome (see 188400), including CAFS. In 1 (4%) of 23 patients with interrupted aortic arch and 1 (4%) of 22 patients with truncus arteriosus, McElhinney et al. (2003) identified heterozygosity for a missense mutation in the NKX2-5 gene (R25C; 600584.0004). Karkera et al. (2007) identified a mutation in the GDF1 gene (602880.0002) in an individual with DORV. Heathcote et al. (2005) used autozygosity mapping of a large consanguineous Kuwaiti family segregating PTA to map the causative locus to chromosome 8p21. They subsequently identified homozygosity for a missense mutation in the NKX2-6 gene (611770.0001) in all affected individuals. Kodo et al. (2009) screened the genomes of 21 unrelated Japanese patients with nonsyndromic persistent truncus arteriosus and identified heterozygosity for a 2-bp deletion (601656.0001) and a missense mutation (601656.0002) in the GATA6 gene, respectively, in 2 probands. The 2-bp deletion was also present in the first proband's father and sister, both of whom had pulmonary stenosis. The sister also had patent ductus arteriosus and atrial septal defect. Atrial septal defect was also present in the first proband. The second proband's mutation occurred de novo, and neither was found in 182 Japanese controls. In 2 (15.4%) of 13 Italian patients with DORV, De Luca et al. (2011) identified heterozygosity for 2 different missense mutations in the ZFPM2 gene, E30G (603693.0002) and I227V (603693.0006). In a 10-year-old Chinese boy with Langer-Giedion syndrome (150230) and DORV, Tan et al. (2012) identified a de novo balanced chromosomal translocation t(8; 18)(q22;q21) that appeared to disrupt the ZFPM2 gene on chromosome 8q23. Analysis of the ZFPM2 gene in 145 Chinese patients with conotruncal defects, including 95 with tetralogy of Fallot, 38 with sporadic DORV, and 12 with transposition of the great arteries, revealed 5 heterozygous missense mutations in patients with DORV (see, e.g., 603693.0004 and 603693.0008) that were not found in 250 Chinese controls in whom conotruncal heart disease had been excluded by echocardiography. No mutations were identified in the patients with TOF or TGA. Tan et al. (2012) suggested that ZFPM2 variants might be a common cause of DORV. - Reviews Obler et al. (2008) reviewed published cases of double-outlet right ventricle and discussed etiology and associations.