CHARGE: an association or a syndrome?

INTRODUCTION: CHARGE "association" is a rare clinical entity with multiple congenital anomalies that necessitates a multidisciplinary approach. Its diagnosis is important not only for the pediatric surgery practice but also for the otorhinolaryngology practice as it complicates with a number of major surgical anomalies. The aim of this paper is to present the latest evidences on the genetic basis of the disease.

MATERIALS AND METHODS: In order to evaluate, a computed literature review was undertaken using PubMed and OMIM databases.

RESULTS: Heterozygous mutations within the chromodomain helicase DNA binding protein 7 (CHD7) were reported in every two of three CHARGE patients. CHD protein family is located on chromosome 8q11.2 and is known to regulate chromatin remodeling which plays an essential role in the developmental gene expression. That is why the haploinsufficiency of CHD7 gene due to heterozygous mutations results in not only the postnatal but also the prenatal developmental regulation errors. The wide expression of this gene in the prenatal period overlaps with the broad spectrum of the phenotypic symptoms of the disease.

CONCLUSION: CHD7 gene haploinsufficiency is expected to be the underlying basis of CHARGE. Even though the genetic basis is unsolved in one-third of the patients, the current evidence supports the term "syndrome" rather than an "association" should be more appropriate for CHARGE.