The eye - the window to the soul of the diagnosis: CHARGE Syndrome, a case report

Abstract

The modality of inheritance in CHARGE syndrome is autosomal dominant, classically triggered by mutations in the chromo-domain helicase DNA binding protein-7 (CHD7) gene. CHARGE syndrome is characterized by the variable occurrence of coloboma, heart defects, atresia of the choanae, retarded growth and development, genital hypoplasia, ear anomalies and deafness. In this report, we describe an infant with a typical phenotype characterized by severe psychomotor retardation, facial asymmetry, coloboma, cortical blindness, unilateral choanal atresia, congenital heart anomalies, genital hypoplasia, cranial nerve IX/X dysfunction and global developmental delay that was diagnosed clinically. Following clinical diagnosis a complete sequencing of the CHD7 gene was carried out at the Institute for Medical Diagnostics GmbH in Ingelheim, Germany. Genomic DNA was screened for mutations in the CD7 gene (OMMIM 608892) on chromosome 8q12.1 The codon exon 2-38 and the respective exon-intron boundaries were amplified by polymerase chain reaction and analysed by direct sequencing. Resulting sequence data were compared with the reference sequence NM_017880.3 No mutation in CHD7 gene was detected as a genetic cause for the clinical phenotype of the patient. The MPLA multiplex ligation-dependent probe amplification analysis showed no copy number variation in the CHD7 gene. This case report underscores the importance of a detailed family history and physical examination in the diagnosis of CHARGE syndrome. Additionally, it provides valuable insight into the pathogenesis and clinical presentation of the syndrome as well as highlighting the benefits of a multidisciplinary approach. With supportive nurturing care, children with CHARGE syndrome can overcome the associated disabilities and develop necessary motor skills and a life-style enhancing level of fitness.