Parents

CHD5 encodes for a component of a protein complex involved in regulation of chromatin conformation and DNA accessibility. CHD5 is mainly expressed in the brain, where it regulates several processes important for brain development.

Main clinical features
Patients with a genetic variant in CHD5 have variable manifestations, some of which appear early on in life (delays in acquiring developmental milestones such as language and walking) and other which are revealed later on during childhood or adolescence. These symptoms include intellectual disability, autism, obsessive-compulsive disorder, epilepsy, and decreased muscular tone.

Prevalence
CHD5-related disorders are likely very rare. Less than 20 individuals have been described so far worldwide but it is possible that this disorder is underdiagnosed because of its clinical variability.

Inheritance
Humans present with 23 pairs of chromosomes. One chromosome of each pair is inherited from the mother and the other from the father. As a consequence, there are two copies of each gene.

CHD5-related disorders follow autosomal dominant inheritance, meaning that the disruption of a single copy of the gene is sufficient to cause the disease. In most cases, the disease-causing mutations arise during or after fertilization and are therefore not found in the parents. In these cases, the recurrence risk for future pregnancies in the family is considered low (probably <1%).

Few familial cases have been reported, where the disease-causing CHD5 variants had been inherited from mildly affected or unaffected parents. In these cases, the recurrence risk for future pregnancies in the family is 50%.