Clinical phenotype and genetic analysis of 7 neonates with CHARGE syndrome caused by CHD7 gene variants

To study the clinical manifestations and genetic characteristics of CHARGE syndrome (CS) in neonates with CHD7 gene variants.

A retrospective analysis was performed on 7 neonates with CS who were diagnosed and treated at Anhui Provincial Children's Hospital from March 2019 to August 2025. Genetic sequencing was conducted on the neonates and their parents.

All 7 neonates presented within 2 days of birth. Five presented with respiratory distress as the primary complaint; six had patent ductus arteriosus (PDA); and all 7 had an atrial septal defect (ASD), dysphagia, and external ear malformations. Three exhibited ocular abnormalities, including congenital cataracts, optic nerve hypoplasia, and optic disc hypoplasia. Five neonates died during the neonatal period; one died at 1 year 9 months of age from severe pneumonia; one was followed up to 4 months of age and remained unable to feed orally, relying entirely on nasogastric tube feeding. All 7 neonates harbored de novo heterozygous CHD7 variants, including five novel variants not previously reported: c.5608-1G>A, c.687del, c.481C>T, c.3378G>C, and an 8q12.1-q12.3 deletion (950.29 kb).

CS presents with complex and diverse clinical features. Neonates exhibiting multisystem abnormalities such as feeding difficulties, respiratory distress, and external ear deformities warrant suspicion of CS. Early genetic testing facilitates identification of causative variants and provides essential information for genetic counseling. The novel CHD7 variants identified in this study expand the mutation spectrum of CS in China.