From the Guidelines
CHARGE syndrome is a genetic disorder caused by mutations in the CHD7 gene on chromosome 8, as identified in the most recent study 1. The CHD7 gene provides instructions for making a protein involved in regulating gene expression during early embryonic development. Mutations in this gene disrupt normal development of various body systems, leading to the characteristic features of CHARGE syndrome, including coloboma, heart defects, atresia of nasal choanae, retardation of growth and development, genitourinary anomalies, and ear anomalies. Some key points to consider in the diagnosis and management of CHARGE syndrome include:
- Genetic testing, such as chromosomal microarray or CHD7 gene sequencing, can confirm the diagnosis, as noted in 1.
- Prenatal testing is possible if a familial mutation has been identified.
- Genetic counseling is recommended for affected individuals and their families to understand inheritance patterns and recurrence risks.
- While there is no cure for CHARGE syndrome, early diagnosis through genetic testing allows for proactive management of associated medical issues and developmental support.
- Treatment is focused on addressing individual symptoms and may involve a multidisciplinary team of specialists. Understanding the genetic basis of CHARGE syndrome is crucial for accurate diagnosis, appropriate medical management, and family planning considerations, as highlighted in 1 and supported by earlier studies such as 1.
The genetic basis of CHARGE syndrome is well-established, with mutations in the CHD7 gene being the primary cause, as stated in 1. This knowledge is essential for providing appropriate care and support to individuals with CHARGE syndrome.
In terms of specific genetic details, the CHD7 gene is located on chromosome 8 and provides instructions for making a protein involved in regulating gene expression during early embryonic development, as noted in 1. Mutations in this gene can disrupt normal development of various body systems, leading to the characteristic features of CHARGE syndrome.
Overall, the genetic basis of CHARGE syndrome is a critical aspect of understanding and managing this complex condition, and genetic testing and counseling are essential components of care for individuals with CHARGE syndrome, as emphasized in 1.
From the Research
Genetic Basis of CHARGE Syndrome
The genetic basis of CHARGE syndrome is attributed to mutations in the CHD7 gene, which encodes for the chromodomain helicase DNA-binding protein 7 2, 3, 4, 5.
- Mutations in the CHD7 gene are found in approximately 60% of individuals with CHARGE syndrome 2.
- The CHD7 gene is located on chromosome 8q12.1 and is responsible for a wide range of tissues and systems affected in CHARGE syndrome 5.
- The majority of mutations in the CHD7 gene predict premature truncation of the protein, leading to haploinsufficiency 3, 4.
- Novel variants in the CHD7 gene have been discovered, expanding the mutational spectrum of the gene and the phenotype of CHARGE syndrome 5.
Mutation Distribution and Phenotypic Correlation
- Mutations are distributed throughout the coding exons and conserved splice sites of CHD7 4.
- The mutation-positive group is more likely to exhibit cardiovascular malformations, coloboma of the eye, and facial asymmetry 4.
- There may be a positive correlation between exon location and phenotype 5.
- The expression of Chd7 in the outflow tract of the heart, optic vesicle, facio-acoustic preganglion complex, brain, olfactory pit, and mandibular component of the first branchial arch has been shown in mouse embryo whole-mount and section in situ hybridization 4.
Genetic Testing and Diagnosis
- Molecular diagnostic testing for CHD7 mutation has been available in a clinical setting since 2005 3.
- Genetic testing helps clarify the phenotypic and genotypic spectrum to facilitate diagnosis, thus promoting optimal follow-up, treatment, and appropriate genetic counselling 2.
- Whole Exome Sequencing (WES) can be used to investigate new variants in the CHD7 gene 5.