cardiofaciocutaneous syndrome
MIM.115150 7q34
Cardiofaciocutaneous (CFC) syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation.
The cardiofaciocutaneous (CFC) syndrome can be caused by gain of function mutations in 1 of 4 different genes: KRAS (MIM.190070), BRAF (MIM.164757), MEK1 (MIM.176872), or MEK2 (MIM.601263). The protein products of these genes interact in a common RAS/ERK pathway that regulates cell differentiation, proliferation, and apoptosis.
It phenotypically overlaps with Noonan and Costello syndrome, which are caused by mutations in PTPN11 and HRAS, respectively.
Synopsis
hydrocephalus
olygohydramnios
normal stature
pyloric stenosis
cutaneous syndactyly of toes
bilateral transverse palmar creases
postnatal short stature
failure to thrive
relative macrocephaly
dolichocephaly
prominent forehead
bitemporal narrowing
shallow orbital ridges
prominent philtrum
coarse facial features
micrognathia
posteriorly rotated ears
earlobe creases
hearing loss
ptosis
nystagmus
strabismus
down-slanting palpebral fissures
hypertelorism
exophthalmos
epicanthal folds
myopia
loss of visual acuity
absence of eyebrows and eyelashes
nose
short upturned nose
bulbous nasal tip
depressed nasal bridge
submucous cleft palate
high-arched palate
atrial septal defects
pulmonic stenosis
hypertrophic cardiomyopathy
splenomegaly
poor feeding in neonatal period
delayed bone age
osteopenia
hyperextensible fingers
multiple palmar creases
multiple plantar creases
severe atopic dermatitis
ichthyosis
hyperkeratosis (especially extensor surfaces)
cavernous hemangioma
multiple palmar creases
sparse hair
curly hair
slow-growing hair
absence of eyebrows and eyelashes
nild to moderate mental retardation
seizures
hypotonia
hypertonia
hydrocephalus
cortical atrophy
frontal lobe hypoplasia
hypoplasia or absence of the corpus callosum
brain stem atrophy
Etiology
germline heterozygous mutations
Differential diagnosis
Noonan syndrome (PTPN11 germline mutations)
Costello syndrome (HRAS germline mutations)
CFC-like phenotype and the same deletion of chromosome region 12q21.2q22 (12749059)
See also
dysregulation of the RAS-RAF-ERK pathway
References
Schubbert S, Shannon K, Bollag G. Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer. 2007 Apr;7(4):295-308. PMID: 17384584
Niihori T, Aoki Y, Narumi Y, Neri G, Cave H, Verloes A, Okamoto N, Hennekam RC, Gillessen-Kaesbach G, Wieczorek D, Kavamura MI, Kurosawa K, Ohashi H, Wilson L, Heron D, Bonneau D, Corona G, Kaname T, Naritomi K, Baumann C, Matsumoto N, Kato K, Kure S, Matsubara Y. Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. Nat Genet. 2006 Feb 12; PMID: 16474404
Kavamura MI, Zollino M, Lecce R, Murdolo M, Brunoni D, Alchorne MM, Opitz JM, Neri G. Absence of 12q21.2q22 deletions and subtelomeric rearrangements in cardiofaciocutaneous (CFC) syndrome patients. Am J Med Genet A. 2003 Jun 1;119(2):177-9. PMID: 12749059