Further delineation of cardio-facio-cutaneous syndrome: clinical features of 38 individuals with proven mutations.
BACKGROUND
Cardio-facio-cutaneous syndrome (CFC) is a multiple congenital anomaly/mental retardation syndrome named because of a characteristic facies, cardiac anomalies, and ectodermal abnormalities. While considerable literature describes the main features, few studies have documented the frequencies of less common features allowing a greater appreciation of the full phenotype.


METHODS
We have analysed clinical data on 38 individuals with CFC and a confirmed mutation in one of the genes known to cause the condition. We provide data on well-established features, and those that are less often described.


RESULTS
Polyhydramnios (77%) and prematurity (49%) were common perinatal issues. 71% of individuals had a cardiac anomaly, the most common being pulmonary valve stenosis (42%), hypertrophic cardiomyopathy (39%), and atrial septal defect (28%). Hair anomalies were also typical: 92% had curly hair, 84% sparse hair, and 86% absent or sparse eyebrows. The most frequent cutaneous features were keratosis pilaris (73%), hyperkeratosis (61%) and nevi (76%). Significant and long lived gastrointestinal dysmotility (71%), seizures (49%), optic nerve hypoplasia (30%) and renal anomalies, chiefly hydronephrosis (20%), were among the less well known issues reported.


CONCLUSIONS
This study reports a broad range of clinical issues in a large cohort of individuals with molecular confirmation of CFC.
C M
CM
Armour
J E
JE
Allanson
D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D019465:Craniofacial Abnormalities / Q000235:genetics*; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005260:Female; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics; D048369:MAP Kinase Kinase 1 / Q000235:genetics; D048370:MAP Kinase Kinase 2 / Q000235:genetics; D008297:Male; D009154:Mutation; D010641:Phenotype; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D013577:Syndrome; D018631:ras Proteins / Q000235:genetics
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482128:MAP2K2 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins