Char Syndrome

Char syndrome is a genetic disorder that is characterized by 3 key features: abnormal facial appearance, a defective heart called patent ductus arteriosus and abnormalities of the hand. It is caused by mutations in the TFAP2B gene that hinders the development of the heart, face and limbs. It is a rare genetic condition and only a handful of families have been identified with this syndrome globally.

Char syndrome is inherited in the autosomal dominant manner. Individuals affected by Char syndrome pose a 50% risk of passing the gene mutation and the disorder on to each of their children. However, new mutations in this gene can cause Char syndrome in people with no family history of this condition.

Signs and Symptoms of Char Syndrome

People with Char syndrome have distinctive facial features such as:

Flat nasal bridge and cheek bones
Wide eyes with droopy eyelids and the corners of eyes point downward
The tip of the nose appears broad and flat.
The distance between the nose and upper lip is shorter than normal
The mouth is triangular in shape with thick, prominent lips.

Hand abnormalities related to Char syndrome include missing or shortened middle portion of the fifth finger. Some abnormal features of the feet have been found, but are rare.

The abnormal heart condition seen in people with Char syndrome is called patent ductus arteriosus and is common in most newborns with Char syndrome. The ductus arteriosus forms a link between the aorta and the pulmonary artery before birth.

In normal babies, this link closes right after birth, but in the case of babies with this syndrome, this connection remains open. In the absence of medical intervention, babies with this heart defect suffer from poor feeding and weight gain as well as rapid breathing. Severe cases of patent ductus arteriosus result in heart failure. This defect also makes people more prone to infection.

Char syndrome also has some less common features including:

Hypodontia or missing second / third molars
Hearing abnormalities
Impaired vision
Delayed development
Parasomnia or abnormal behavior during sleep.

Diagnosis and Treatment

Char syndrome is diagnosed by examining clinical features and establishing the presence of abnormal facial appearance, patent ductus arteriosus, and absent or shortened middle section of the fifth finger. This condition can also be detected by genetic testing, as TFAP2B is the only gene whose mutation causes Char syndrome. Analysis of the TFAP2B gene sequence is found to detect mutations in nearly 50% of patients.

Treatment of heart defects in newborns involves surgical ligation of the connection between two arteries. Other symptoms such as vision problems, hearing impairment and developmental delay are treated using routine methods.

Genetic counseling is offered to families identified with this specific mutation and they are encouraged to go through prenatal testing for pregnancies that are at risk of transferring the mutation to the child.

Genetics of Char Syndrome

Char syndrome is caused by mutations in the TFAP2B gene, which codes for a protein called transcription factor AP-2β. Transcription factors are proteins that bind to specific DNA regions and help regulate the expression of specific genes. Transcription factor AP-2β controls the expression of genes involved in prenatal development. This factor plays a key role in the structural formation of heart, face and limbs.

Mutations in the TFAP2B gene leads to changes in the structure of transcription factor AP-2β. Some type of mutations prevents the binding of the factor to the DNA, while others render it unfit to control gene activity. In the absence of a functional transcription factor AP-2β, the normal development of body parts before birth is disrupted, leading to the abnormal facial and limb features.