Cardio-facio-cutaneous, syndrome

[MIM 115 150615 278615 279615 280]

Extremely rare. This syndrome is phenotypically close to the  Noonan and Costello syndromes (see these terms) and is part of the family of the RASopathies (see this term). A sporadic mutation of one of the following genes causes this syndrome: BRAF (> 80 %), MEK1 (MAP2K1) or 2 (MAP2K2), or KRAS.


Clinical picture:

-         facial anomalies: relative macrocephaly with a broad forehead, hypertelorism, ptosis, abnormalities of the outer ear, down-  or backslanting palpebral fissures

-         heart defects (75%): pulmonary stenosis (40%); ASD, VSD, hypertrophic cardiomyopathy (40%)

-         skin abnormalities: hyperkeratosis with sometimes ichthyosis; eczematous lesions; rare or even eyelashes and eyebrows;  absent, sparse and curly hair

-         mental retardation

-         neonatal period: polyhydramnios, prematurity, hyponatremia, feeding difficulties, systemic hypertension, respiratory difficulties


but also:

-         nystagmus or strabismus, small optic nerve

-         short hands with deep skin creases

-         hypotonia, hydrocephalus, convulsions; sometimes Arnold-Chiari malformation (see this term)

-         severe feeding difficulties resulting in a failure to thrive (sometimes < 5 percentile)

-         intestinal malrotation

-         gastro-esophageal reflux

-         tendency to develop benign (giant cell tumors) or malignant (hepatoblastoma, lymphoma, acute lymphoblastic leukemia) tumors


Anesthetic implications: 

echocardiography, blood formula; mental retardation, small stature; caution in mobilizing the occipital-cervical junction if there is an Arnold-Chiari malformation.


References : 

-         Verloes A, Cave H. Syndrome de Noonan et RASopathies apparentées, 
In Syndromes dysmorphiques, édité par D Lacombe et N Philip, Série Progrès en Pédiatrie, Doin 2013, p 13-26.

-         Ramsey KNW, Loichinger MH, Slavin T, Kuo S, Seaver LH. 
The perinatal presentation of craniofaciocutaneous syndrome. 
Am J Med Genet Part A 2014; 164A: 2036-42.

-        Lam H, Dare S, Nguyen T, Austin T. 
Anesthesia for a pediatric patient with cardiofaciocutaneous syndrome. 
A&A Case Reports 2015; 4: 95-6


Updated: November 2019