Char Syndrome

Clinical characteristics: Char syndrome is characterized by the triad of typical facial features, patent ductus arteriosus, and aplasia or hypoplasia of the middle phalanges of the fifth fingers. Typical facial features are depressed nasal bridge and broad flat nasal tip, widely spaced eyes, downslanted palpebral fissures, mild ptosis, short philtrum with prominent philtral ridges with an upward pointing vermilion border resulting in a triangular mouth, and thickened (patulous) everted lips. Less common findings include other types of congenital heart defects, other hand and foot anomalies, hypodontia, hearing loss, myopia and/or strabismus, polythelia, parasomnia, craniosynostosis (involving either the metopic or sagittal suture), and short stature.

Diagnosis/testing: The diagnosis of Char syndrome is established in a proband with suggestive clinical findings and/or a heterozygous pathogenic variant in TFAP2B identified by molecular genetic testing.

Management: Treatment of manifestations: Management of patent ductus arteriosus after the immediate newborn period is determined by the degree of shunting from the aorta to the pulmonary artery; options are surgical ligation or ductal occlusion at catheterization. Hypodontia/tooth anomalies, vision problems, hearing loss, other hand/foot anomalies, parasomnias, and craniosynostosis are treated in a routine manner.

Surveillance: Assessment for signs and symptoms of sleep problems at each visit; monitoring of head shape and size at each visit during the first year of life; vision and hearing screening annually or as clinically indicated; dental evaluations every six months starting at age three years.

Genetic counseling: Char syndrome is inherited in an autosomal dominant manner. The proportion of cases caused by a de novo pathogenic variant is unknown. If a parent of the proband is affected, the risk to the sibs is 50%. When the parents are clinically unaffected, the risk to the sibs of a proband appears to be low. Each child of an individual with Char syndrome has a 50% chance of inheriting the pathogenic variant and having the disorder. If the pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.