Cornelia de Lange Syndrome Caused by an Intragenic Heterozygous Deletion in RAD21 Detected through Very-High-Resolution Chromosomal Microarray Analysis

Cornelia de Lange syndrome is a genetic and clinically heterogeneous entity, caused by at least five genes. It is characterized by short stature, gestalt facies, microcephaly, neurodevelopmental disorders, and other anomalies. In this report, we present a 13-year-old female patient with microcephaly, cleft palate, polydactyly, short stature, triangular facies, frontal bossing, a bulbous nose, an overfolded helix, limited pronosupination, and an anomalous uterus. No neurodevelopmental disorders were reported. A chromosomal microarray analysis of 6.5 million markers was performed in the proband and her parents. The results showed a de novo heterozygous microdeletion of exons 9-14 within , which confirmed the diagnosis of Cornelia de Lange syndrome type 4. Our patient did not show any neurologic phenotype (until the time of diagnosis), although neurodevelopmental disorders are frequently present in patients with Cornelia de Lange syndrome type 4, and despite carrying a deletion that was larger than previously reported. Therefore, unknown genetic modifiers or intrinsic mechanisms of variants may exist and should be studied.