Cardio-facio-cutaneous syndrome (CFC) is a multiple congenital anomaly disorder characterized by craniofacial dysmorphia, ectodermal abnormalities, congenital heart defects, and developmental and growth delay. Neurological complications associated with CFC remain to be clearly defined. Recent discovery of causative mutations in genes of the MAPK pathway (BRAF, MEK1, and MEK2) now permit accurate molecular diagnosis of CFC. The aim of the study was to characterize neurological features of participants with molecularly-confirmed CFC. Medical records, and laboratory and imaging data were reviewed for 39 mutation-positive individuals with CFC. Participants with a clinical diagnosis of CFC but a negative result on mutation screening of the BRAF, MEK1, and MEK2 genes were excluded from the study. Mean age of participants was 9 years 4 months (range 18mo-24y); there were 24 females and 15 males. Mutations in B RA F were present in 32 participants, MEK1 in five, and MEK2 in two participants. Hypotonia, motor delay, speech delay, and learning disability were universally present in this cohort. Macrocephaly was present in 13 participants, ptosis in 11, strabismus in 14, and nystagmus in 11 of the 22 participants who underwent a neurological exam. Corticospinal tract findings were present in seven participants. Ventriculomegaly or hydrocephalus was present in 14 of 32 participants who underwent brain imaging. Other findings on magnetic resonance imaging included prominent Virchow-Robin spaces (n=6), abnormal myelination (n=4), and structural anomalies (n=5). Seizures were present in 15 participants. No specific genotype-phenotype correlation was observed.
Mitogen-activated protein kinase
Neurofibromatosis type 1