Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

CHARGE Syndrome (Hall-Hittner Syndrome) [Q87.8]

OMIM numbers: 214800, 608892 (CHD7)

Dr. med. Imma Rost, Dr. rer. nat. Christoph Marschall

Scientific Background

CHARGE syndrome (Hall-Hittner syndrome) is a disorder with autosomal dominant inheritance although it mostly occurs sporadically with a frequency of 1 in 10,000. The acronym CHARGE stands for coloboma, heart defects, choanal atresia, retarded growth and development, genital abnormalities and ear anomalies. According to Verloes (2005) major criteria are coloboma, choanal atresia and hypoplasia of the semicircular canals. Minor criteria are rhombecephalic dysfunction (brainstem and cranial nerve III to XII anomalies, including sensorineural deafness), hypothalamo-hypophyseal dysfunction (including GH and gonadotropin defects) malformation of the ear (internal or external), malformation of mediastinal organs (heart, esophagus) and intellectual disability. Diagnosis is confirmed if three major criteria are present or two major and two minor criteria. Clinical variability is extensive. Life expectancy depends on the severity of the malformations. Up to one-third of affected patients die within the first six months of life. Most of the time a psychomotor developmental delay is present but occasionally intelligence lies within the normal range.  

Mutations in the CHD7 gene can be identified in 60-70% of the patients (CHD: chromodomain helicase DNA-binding protein 7). CHD proteins belong to the chromatin remodeling factors and influence chromatin structure and gene expression. Therefore, they play a significant role in embryonic development. The mutations are spread through the whole coding region of the CHD7 gene (exon 2-38). Truncating mutations which lead to an early stop of protein synthesis are found in the majority of cases. Deletions are rare. There is no genotype-phenotype correlation. A germline mosaicism was detected in at least one case. This means that a low risk of recurrence cannot totally be excluded even if no mutation was found in both parents.