Smith-Magenis syndrome is a microdeletion syndrome associated with a clinically recognizable behavioral and physical phenotype due to an interstitial deletion of 17p11.2. Recent evidence suggests that haploinsufficiency of the retinoic acid induced 1 gene (RAI1) is probably responsible for the behavioral, neurological, otolaryngological, and craniofacial aspects of SMS, whereas more variable features such as heart and renal defects are probably due to hemizygosity of other genes in the 17p11.2 region [Slager et al., 2003].
Neurobehavioral manifestations typical of this syndrome include mental retardation, sleep dysfunction with inverted circadian rhythm of melatonin, hyperactivity, stereotypy, selfhugging behavior, and self-injurious behaviors [Chen et al., 1996; Smith et al., 2002a]. Common physical manifestations include short stature, brachycephaly, broad face, midface hypoplasia, bowed or tented upper lip, ocular abnormalities, middle ear and laryngeal abnormalities, hoarse voice, scoliosis, hearing loss, signs of peripheral neuropathy, and hypercholesterolemia [Chen et al., 1996; Smith et al., 2002a,b]. Cleft palate, renal, or urinary tract anomalies, thyroid dysfunction, immune system dysfunction, seizures, and congenital heart defects occur in a significant minority of patients [Chen et al., 1996; Smith et al., 2002a]. Greenberg et al. [1996] found structural heart defects by echocardiography in nine of 27 patients studied (33%). A variety of cardiac defects, including septal defects, valvular abnormalities, and tetralogy of Fallot have been described in patients with Smith-Magenis syndrome (Table I). In addition to the patients with documented structural heart defects listed in Table I, two patients reported by Slager et al. [2003] were noted to have cardiovascular anomalies (individual SMS126 with a typical deletion and individual HOU142-540 with a small deletion), but no details were provided. Also, six patients with murmurs suggestive of congenital heart defects but without confirmatory imaging were described in the early literature [Stallard et al., 1984;Smith et al., 1986;Stratton et al., 1986]. We are aware of no previous reports of total anomalous pulmonary venous return in patients with Smith-Magenis syndrome.
Two of our patients with Smith-Magenis syndrome have congenital heart defects including total anomalous pulmonary venous return. The first is a 15-year-old boy with subdiaphragmatic total anomalous pulmonary venous return that was diagnosed and repaired in the neonatal period. In addition to the cardiovascular abnormality, he had a cleft palate that was