To the Editor:
RASopathies, a class of developmental disorders, are caused by mutations in genes that encode protein components of the RAS/mitogen-activated protein kinase (MAPK) pathway. Each syndrome exhibits its phenotypic features; however, because all of them cause dysregulation of the RAS/MAPK pathway, there are numerous overlapping phenotypic features between the syndromes including cardiac defects, cutaneous abnormalities, characteristic facial features, neurocognitive impairment, and increased risk for developing some neoplastic disorders.
Cardiofaciocutaneous (CFC) syndrome is a RASopathy and is a genetic sporadic disease characterized by multiple congenital anomalies associated with mental retardation. It has a complex dermatological phenotype with many cutaneous features that can be helpful to differentiate CFC syndrome from Noonan and Costello syndromes, which also are classified as RASopathies.
A 3-year-old girl presented with skin xerosis and follicular hyperkeratosis of the face, neck, trunk, and limbs (Figure 1). Facial follicular hyperkeratotic papules on an erythematous base were associated with alopecia of the eyebrows (ulerythema ophryogenes). Hair was sparse and curly (Figure 2A). Facial dysmorphic features included a prominent forehead with bitemporal constriction, bilateral ptosis, a broad nasal base, lip contour in a Cupid’s bow, low-set earlobes with creases (Figure 2B), and a short and webbed neck.
Figure 1. Follicular hyperkeratosis of the limbs (A and B) and trunk (C).
Figure 2. Sparse and curly hair (A) and low-set earlobes with creases (B).
Congenital heart disease, hypothyroidism, bilateral hydronephrosis, delayed motor development, and seizures were noted for the first 2 years. Brain computed tomography detected a dilated ventricular system with hydrocephalus. There was no family history of consanguinity.
Pregnancy was complicated by polyhydramnios and preeclampsia. The neonate was delivered at full-term and was readmitted at 6 days of age due to respiratory failure secondary to congenital chylothorax. Cardiac malformation was diagnosed as the ostium secundum atrial septal defect and interventricular and atrioventricular septal defects. Up to this point she was being treated for Turner syndrome.