Smith–Magenis syndrome: Report of morphological and new functional cardiac findings with review of the literature

Abstract

Smith–Magenis syndrome (SMS) is a genetic disorder characterized by multiple congenital anomalies, sleep disturbance, behavioral impairment, and intellectual disability. Its genetic cause has been defined as an alteration in the Retinoic Acid‐Induced 1 gene. Cardiac anomalies have been reported since the first description of this condition in patients with 17p11.2 deletion. Variable cardiac defects, including ventricular septal defects, atrial septal defects, tricuspid stenosis, mitral stenosis, tricuspid and mitral regurgitation, aortic stenosis, pulmonary stenosis, mitral valve prolapse, tetralogy of Fallot, and total anomalous pulmonary venous connection, have been anecdotally reported and systematic case series are still lacking. Herein, we define the spectrum of the cardiac phenotype and describe for the first time the cardiac function in a large cohort of pediatric patients with SMS. Revision of the literature and correlations between genotype and cardiac phenotype was performed.

Smith Magenis syndrome: First case of congenital heart defect in a patient with Rai1 mutation

“…Recurrent cardiac anomalies in patients affected by SMS are ventricular and atrial septal defects, tetralogy of Fallot, anomalous pulmonary venous connection, and valvular disease (Lei et al, 2016). Pulmonary valve stenosis is less common than other cardiac malformations; it can occur as isolated or in association with other cardiac defects and the severe form of stenosis requires correction within the first year of life (Greenberg et al, 1996; Lei et al, 2016; Onesimo et al, 2021; Rive Le Gouard et al, 2021).…”

“…Patients affected by SMS exhibit a complex clinical phenotype characterized by neurological and behavioral impairment, growth retardation, sleep disturbance, childhood onset obesity, craniofacial skeletal abnormalities, and multiple congenital defects, including a wide spectrum of congenital heart diseases (Elsea & Girirajan, 2008). On this regard, in individuals diagnosed with SMS the cardiac features most frequently detected are septal defects, Tetralogy of Fallot, valvular abnormalities, and anomalous pulmonary venous connection, even though cardiac involvement can occur as isolated systolic and/or diastolic dysfunction of both ventricles in the absence of evident structural malformations (Onesimo et al, 2021). To date, cardiac anomalies have been detected only in patients with 17p11.2 deletion, whereas no heart defects have been described in patients carrying RAI1 variants so far (Edelman et al, 2007).…”

Smith-Magenis Syndrome—Clinical Review, Biological Background and Related Disorders

“…Cardiovascular. The frequency of congenital heart defects (CHDs) varies from 25% [ 34 ] to 45% [ 28 ]. The most frequent CHDs are atrial septal defects, ventricular septal defects, tetralogy of Fallot, valvular abnormalities, and total anomalous pulmonary venous connection [ 34 ].…”

“…The frequency of congenital heart defects (CHDs) varies from 25% [ 34 ] to 45% [ 28 ]. The most frequent CHDs are atrial septal defects, ventricular septal defects, tetralogy of Fallot, valvular abnormalities, and total anomalous pulmonary venous connection [ 34 ]. Arrhythmias and conduction disorders are present in 12% of subjects and include right conduction delay and ventricular pre-excitation [ 9 , 34 ].…”

“…The most frequent CHDs are atrial septal defects, ventricular septal defects, tetralogy of Fallot, valvular abnormalities, and total anomalous pulmonary venous connection [ 34 ]. Arrhythmias and conduction disorders are present in 12% of subjects and include right conduction delay and ventricular pre-excitation [ 9 , 34 ]. Importantly, echographic signs of dysfunction of both the right and the left ventricle have been detected in all the patients of a cohort of 24 SMS individuals, raising concerns about the possible occurrence of heart failure [ 34 ].…”