CFC International Conference

July 28-30, 2011Rosemont, Illinois

Giovanni Neri and Giorgia MancanoInstitute of Medical GeneticsCatholic University School of

MedicineRome, Italy

History of CFC History of CFC SyndromeSyndrome

19861986

CFC patients (Reynolds et al., 1986)CFC patients (Reynolds et al., 1986)

Montana, Fall of 1983

19911991

19991999

CCaring, FFacilitating

& CConnecting

20002000

FIRST INTERNATIONAL CFC CONFERENCE SALT LAKE FIRST INTERNATIONAL CFC CONFERENCE SALT LAKE CITY CITY

20012001

20032003

20062006

20062006

2009

20092009

4hpf 12hpf 24hpf 48hpf

uninjected

BRAF wt

BRAF Q257R

20112011

+/+ +/LSLV600E

20??20??

discovery of a cure for CFC syndrome

CI1040 PD0325901

Rauen et al, AJMG Part C, 2011

Natural History of Natural History of CFCSCFCS

polyhydramnios (62-69%) prematurity (49-52%) macrosomia (34-35%) hypotonia (79-86%) congenital heart defect:

pulmonic stenosis (37-50%) ASD (18-28%) VSD (11-19%)

cryptorchidism (36-66%)

Perinatal PeriodPerinatal Period

percentages obtained from Allanson et al., AJMG Part C, 2011percentages obtained from Allanson et al., AJMG Part C, 2011

failure to thrive (78-83%)

feeding difficulties (40-54%)

hypertrophic cardiomyopathy (24-38%)

skin involvement:

curly/sparse hair (77-93%)

absent/sparse eyebrows (78-

81%)

keratosis pilaris (48-67%)

hyperkeratosis (43-46%)

nevi (36-42%)

deep palmar creases (38-47%)

Infancy & Childhood-1Infancy & Childhood-1

percentages obtained from Allanson et al., AJMG Part C, 2011

Infancy & Childhood-2Infancy & Childhood-2

seizures (31-32%) tactile defensiveness (80%) musculoskeletal defects:

scoliosis (33-34%) kyphosis (17-26%) pectus deformities (44-63%)

developmental delay: short stature (63%) absolute macrocephaly (20-

35%) relative macrocephaly (67-69%) intellectual disability (93-100%)percentages obtained from Allanson et al., AJMG Part C, 2011

No evidence of higher incidence of tumorsNo evidence of higher incidence of tumors

Adolcescence & AdulthoodAdolcescence & Adulthood

no information about puberal

development

worsening of musculo-skeletal

manifestations?

premature aging?

Old AgeOld Age

nothing known so far

urgent need to gather

information

Genotype-Phenotype CorrelationsGenotype-Phenotype Correlations

BRAF MEK P-value

pulmonic stenosis 50% 37% 0.000363

curly / sparse hair 93% 77% 0.014

cryptorchidism 30% 66% 0.04

hydrocephalus 27% 0% > 0.05

intellectual disability

100% 93% > 0.05

pectus deformity 44% 63% > 0.05

Data obtained from Allanson et al., AJMG Part C, 2011