Cornelia De Lange Syndrome Presenting As Hydrops Fetalis Due to Intestinal Atresia.

Cornelia de Lange Syndrome (CdLS) is characterized by growth retardation, severe mental retardation, short stature, a low-pitched growling cry, brachycephaly, low-set and/or posteriorly rotated ears, webbed neck, carp mouth, depressed nasal bridge, hirsute forehead, bushy eyebrows meeting at the midline, hirsutism, malformations of the hands, and structural malformations that mainly involve the genitourinary, cardiac, gastrointestinal, and central nervous systems [Qiao et al., Front Genet 2021; 12: 628890; Mutlu et al., Clin Dysmorphol 2010; 19: 161–163; Li et al., Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021; 38: 1132–1135]. The first description of CdLS was by a Dutch pediatrician, who observed it in two children in 1933 [De Lange, Arch Med Enfants 1933; 36: 713–719]. CdLS is a rare, clinically and genetically heterogeneous, multisystem developmental disorder, diagnosed on the basis of clinical observations. Although almost any organ system can be affected, the neurodevelopmental, craniofacial, gastrointestinal, and musculoskeletal systems are the most commonly involved [Holthusen et al., Tidsskr Nor Laegeforen 1998; 118: 1559–1560; Yuan et al., J Clin Invest 2015; 125: 636–651; Li et al., Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021; 38: 1132–1135; Peng et al., Front Genet 2021; 12: 699894]. The mutations in the SMC1A, SMC3, NIPBL, RAD21 and HDAC8 genes have been identified as responsible for CdLS in some of the cases [Krantz et al., Nat Genet 2004; 36: 631–635; Tonkin et al., Nat Genet 2004; 36: 636–641; Musio et al., Nat Genet 2004; 38: 528–530; Deardorff et al., Am J Hum Genet 2007; 80: 485–494; Deardorff et al., Am J Hum Genet 2012; 90: 1014–1027; Deardorff et al., Nature 2012; 489: 313–317]. The genetic cause underlying is unknown in approximately 30% of CdLS cases. The diagnosis of CdLS is usually made according to the clinical signs after birth. Prenatal diagnosis of CdLS can be made if there are abnormalities such as congenital diaphragmatic hernia, characteristic extremity abnormalities, and facial profile detected by fetal ultrasound. However, routine prenatal ultrasonography is diagnostically unsuccessful in more than two-thirds of CdLS cases with major malformations [Peng et al., Front Genet 2021; 12: 699894; Selicorni et al., Genes (Basel) 2021; 12: 1075]. We present a CdLS case who had non-immune hydrops fetalis (NIHF), which has not been ever reported in the literature.