Abstract:

Objective To analyze the clinical features and gene variation characteristics of 5 children diagnosed with neonatal CHARGE syndrome, and to identify the genetic etiology of the deaths. Methods The clinical data of 5 children were collected. High-throughput sequencing technology was used to detect 5 children with suspected CHARGE syndrome, and Sanger sequencing technology was used to verify the suspicious loci and core family members. Results Clinical features of 5 cases: structural deformity combined with feeding difficulties (both excluded posterior nasal atresia), 2 children with crooked mouth crying, 3 children with nasal cavity stenosis or upper airway collapse syndrome who, due to poor treatment effect, could not be removed from the ventilator and eventually died, 1 patient's family members gave up treatment and died at home; 1 patient is currently being followed up. Family 1 had a frameshift variant of the CHD7 gene c.478del (Y160Tfs*51), family 2 had a nonsense variant of the CHD7 gene c.5428C>T (P.R1810*), and family 3 had a nonsense variant of the CHD7 gene c.6292C>T (P. R2098*), family 4 had a frameshift variant of the CHD7 gene c.4317delA (p.Q1440S fs*3), family 5 had a nonsense variant of the CHD7 gene c.469C>T (P.R157*). The parents of the 5 families did not carry the corresponding variats, and the varians were all de novo. The c.4317delA in family 4 was previously unreported. Conclusion The CHD7 gene mutation may be the pathogenic cause of 5 cases. The genetic cause of death in 4 cases may be system malformation caused by CHD7 gene mutation; for the clinical diagnosis of children with similar multiple malformations, the genetic testing should be actively improved to make the diagnosis clear, so as to improve the clinician's understanding of the disease.

Key words: CHARGE syndrome, CHD7 gene, newborn