Cardiofaciocutaneous syndrome
Cardiofaciocutaneous syndrome is a rare genetic disorder affecting the heart, facial features, and skin, often accompanied by developmental delays and intellectual disability.
Overview
Cardiofaciocutaneous syndrome is a disorder that affects many parts of the body, particularly the heart (cardio-), facial features (facio-), and the skin and hair (cutaneous). People with this condition also have delayed development and intellectual disability, usually ranging from moderate to severe.
Symptoms
- Heart defects: Most commonly pulmonic stenosis, holes between the upper heart chambers, and hypertrophic cardiomyopathy.
- Distinctive facial features: High forehead, widely spaced eyes, downward-slanting eyes, droopy eyelids, a depressed nasal bridge, and low-set ears.
- Skin and hair abnormalities: Dry, rough skin; dark-colored moles; wrinkled palms and soles; and keratosis pilaris. Hair is typically thin, dry, and curly, with sparse eyelashes and eyebrows.
- Developmental and physical issues: Weak muscle tone (hypotonia), feeding difficulties, failure to thrive, unusually large head (macrocephaly), short stature, vision problems, and seizures.
Causes & Risk Factors
The syndrome is caused by variants in several genes that provide instructions for the RAS/MAPK signaling pathway, which is essential for cell growth, division, and differentiation:
- BRAF: Accounts for 75 to 80 percent of cases.
- MAP2K1 and MAP2K2: Account for 10 to 15 percent of cases.
- KRAS: Accounts for fewer than 5 percent of cases.
These variants lead to overactive proteins that interfere with normal development. The condition is part of a group of related disorders known as RASopathies.
Inheritance
Cardiofaciocutaneous syndrome is an autosomal dominant condition, meaning one copy of an altered gene is sufficient to cause the disorder. It usually results from a new (de novo) mutation in people with no family history of the condition.