5 Interesting Facts of Cardiofaciocutaneous syndrome
- Most commonly caused by heterozygous mutation involving the BRAF gene
- Also may be caused by gain-of-function mutations in KRAS, MEK1, or MEK2 genes
- Some phenotypic manifestations closely resemble Noonan phenotype, such as dysmorphic facial features, cardiac defects (pulmonic stenosis, septal defects, hypertrophic cardiomyopathy), and intellectual disability
- Some subtle phenotypic differences in manifestations:
- Blue eyes are more common in patients with Noonan syndrome; broader longer face; coarser facial features; rounder, more bulbous nasal tip and wider nasal base are more suggestive of cardiofaciocutaneous syndrome
- Florid, severe cutaneous findings (eg, follicular keratosis; sparse eyebrows and lashes; ichthyosis) are more suggestive of cardiofaciocutaneous syndrome
- Most infants with cardiofaciocutaneous syndrome have severe and often long-lasting feeding difficulties, whereas infants who have Noonan syndrome have self-limited feeding difficulties
- Central nervous system structural abnormalities are much more common in patients with cardiofaciocutaneous syndrome
- Bleeding diathesis is rare in patients with cardiofaciocutaneous syndrome, but common in patients with Noonan syndrome
- Most patients with cardiofaciocutaneous syndrome develop moderate intellectual disability as opposed to mild or minimal intellectual disability noted in patients with Noonan syndrome
- Differentiate by clinical presentation, clinical diagnostic criteria, and lack of pathogenic genetic variant associated with Noonan syndrome
- Diagnosis is largely based on clinical criteria; mutation analysis identifying distinct pathogenic variants associated with cardiofaciocutaneous syndrome may assist in definitive diagnosis
