FIG 77.3 Facial appearance of deletion 8p23 syndrome Table 77.4 Prevalence of Clinical Features in Patients With Terminal 8p Deletion Clinical Feature Developmental delay/learning difficulties Congenital heart defect Atrioventricular canal defect (with or without pulmonary valve stenosis) Pulmonary valve stenosis (alone) Atrial septal defect Tetralogy of Fallot Heterotaxia Other Facial anomalies Microcephaly Hypospadia Cryptorchidism Epilepsy Frequency (%) 100 70 60 15 10 5 65 55 40 30 25 Cardiac Defects Cardiac malformations are present in two-thirds of the patients, and AVCD is diagnosed in approximately 40% of the cases, documenting a strong association of the atrioventricular septal defect with terminal deletions of 8p.34 In general, the AVCD is complete and often associated with pulmonary valve stenosis In addition, the finding of dextrocardia, abnormalities of the pulmonary and systemic venous returns, common atrium, pulmonary stenosis, single ventricle, and transposition of the great arteries in a number of patients with deletion 8p23 suggest that cardiac laterality defects may be involved.34–36 Nevertheless, the spectrum of CHDs in this syndrome is wide because conotruncal anomalies, ventricular or atrial septal defects, pulmonary valve stenosis, and patent ductus arteriosus have been also reported36 (see Table 77.4) Genetic Defect The syndrome is due to deletion of the distal part of chromosome 8p.35,37 A cluster of genes affecting heart differentiation is located on the distal chromosome 8p GATA4 is considered a candidate gene for heart defects because it affects the initial steps of cardiac morphogenesis and is found to be deleted in majority of patients with deletion 8p and CHD.38 Nevertheless, it is unclear at present if a single gene or several genes in this region have a role in heart differentiation, and positional effects cannot be excluded.36 Microchromosomal Anomalies Deletion 22q11.2 (Digeorge/Velocardiofacial Syndrome) Clinical Features Clinical characteristics of deletion 22q11.2 include CHD, palatal malformations, neonatal hypocalcemia, immune deficit, speech and learning disabilities, facial anomalies such as hypertelorism, “hooded eyelids,” tubular nose, small mouth or micrognathia, auricular abnormalities, and asymmetric crying facies (Fig 77.4 and Table 77.5).39–41 Palatal abnormalities are represented by cleft palate, velopharyngeal incompetence, submucosal cleft palate, bifid uvula, and functional problems such as hypotonia of the velopharyngeal musculature Immunodeficiency occurs as a result of thymic hypoplasia In fact, impaired Tcell production is the primary defect because the role of the thymus is to support the maturation of T cells Hypocalcemia is typically most relevant in the neonatal period and is secondary to hypoparathyroidism However, it may recur in adulthood, especially concomitantly with biologic stress such as fever or surgery Developmental delay is expressed as speech delay, intellectual disability, and learning difficulties in specific areas Psychiatric illness and predisposition to schizophrenia are the most common group of late-onset conditions in adolescent and adult patients.42,43