ocular epibulbar dermoid, and cervical vertebral malformations (Table 77.15).144 Congenital malformations included in the spectrum are CHD, renal anomalies, and rarely central nervous system malformations.144–146 Table 77.15 Prevalence of Clinical Features in Patients With Goldenhar Syndrome Clinical Feature Mandibular hypoplasia Microtia Preauricular tags Conductive hearing loss Velopharyngeal insufficiency Congenital heart defect Conotruncal heart defect Septal defects Abnormal pulmonary venous return/scimitar syndrome Situs and looping defects Left-sided obstructions Other Cervical spine malformation Epibulbar dermoid Cleft lip and/or palate Sensorineural hearing loss Coloboma of the upper eyelid Limb anomalies Genitourinary malformation Pulmonary anomaly Frequency (%) 100 70–90 40–60 60 55 30–50 40 30 15 4 20–40 35 22 15 15 10 10 Cardiac Defects The frequency of CHDs in Goldenhar syndrome is varying in different series, ranging from 5% to 60% in several studies The most common CHDs are conotruncal and septal defects (see Table 77.15).146,147 Conotruncal heart defects include tetralogy of Fallot (classic or with pulmonary atresia), subaortic ventricular septal defect, double-outlet right ventricle, and double aortic arch Cardiac laterality defects in the setting of visceral heterotaxia have also been reported Pulmonary anomalies associated with vascular defects, including Scimitar syndrome (anomalous connection of the right pulmonary veins to the inferior vena cava) associated with hypoplastic right pulmonary artery and lung, have been described.147 The presence and the type of CHD is the clinical feature that most commonly influences prognosis of individuals with Goldenhar syndrome Genetic Defect The diagnosis of Goldenhar syndrome is based on clinical findings because the genetic basis is at present unknown A pathogenetic role of neural crest cell migration abnormalities148 in a group of patients with oculo-auriculo-vertebral spectrum could hypothetically explain the occurrence of conotruncal heart defects and main phenotypical features, including ear, mandible, and neck malformations Heterogeneity of cardiac defects could be related to different pathogenetic causes of the syndrome In fact, environmental, heritable, and multifactorial causes are hypothesized to be implicated.149 Maternal environmental risk factors include the use of vasoactive drugs, maternal diabetes mellitus, multiple gestations, and the use of assisted reproductive technologies In addition, several chromosomal regions or genes are being evaluated for causal relationship Heterotaxy The heterotaxy syndrome is characterized by combination of abnormal arrangement of the abdominal and thoracic organs with complex CHDs, including AVCD, common atrium, anomalous systemic and pulmonary venous drainage, persistent left superior vena cava with unroofed coronary sinus, and conotruncal defects.150 Several syndromes can be associated with partial or complete manifestations of heterotaxy, including polydactyly syndromes (oralfacial-digital, EVC, short rib polydactyly, Smith-Lemli-Opitz, Bardet-Biedl, hydrolethalus, and Joubert syndromes) and VACTERL association.97 A common pathogenetic basis between cardiac laterality defects and these syndromes has been evidenced because molecular studies have demonstrated that several genes responsible for syndromes with heterotaxy are causally involved in ciliary function and/or abnormal processing of proteins with role in Hedgehog signaling.95,151–153 Hedgehog signaling coordinates multiple aspects of left-right lateralization and cardiovascular growth In addition, Sonic Hedgehog knockout mice show CHDs in the setting of heterotaxy and left pulmonary isomerism.154,155 It has been found that perturbations of the different components of Sonic Hedgehog pathway are associated with different developmental errors in patients manifesting partially overlapping features.156,157 The common cardiac manifestations of ciliopathies are partial atrioventricular canal with common atrium and persistent left superior vena cava.97 Types of Anatomic Congenital Heart Defects and Associated Syndromes Patients with specific genetic syndromes often present CHDs related through the pathogenetic basis.10,158 The more common identifiable associations for the different pathogenetic groups are showed in Table 77.16 Table 77.16 Genetic Syndromes Associated to Specific Pathogenetic Groups of Congenital Heart Defect