“A Rare presentation of Cardiofaciocutaneous syndrome: clinical and genetic insights”


Dr.Joepaul Joy, Dr.Sajitha Nair,Dr.SheelaNampoothiri(Genetics), Dr. C Jayakumar,
AIMS, Kochi

Seven year old female child , third child of NCM, term ba, BW of 3.5kg with global development delay and hypertrophic cardiomyopathy on multidisciplinary follow up, history of recurrent cough and wheeze since past five years and was on MDI Budesonide and salbutamol came to the OPD with complaints of cough, running nose since past two weeks and low grade fever and breathing difficulty since one day. 

At admission child was afebrile, conscious, tachypneic with lower chest indrawing. Systemic examination revealed dysmorphic child with Noonan phenotype having multiple lentigines over the body which is more in the upper chest and neck. 
Chest examination showed bilateral rhonchi and crackles . There was no jaundice or organomegaly. 
Differentials of Noonan syndrome, Cardio-facio cutaneous syndrome were considered. 

Counts showed neutrophilic leucocytosis with negative CRP. 
IgE wa >2500IU/mL. 
CXR showed hyperinflated lung fields with cardiothoracic ratio of 0.52. 
LFT/RFT/TFT were normal. 
She was started on antibiotics and nebulized bronchodilators and other supportive measures. 
Peripheral smear showed relative neutrophilia. Echo done showed asymmetric LVH mainly involving IVS, mild AML prolapse, trivial MR with good biventricular function. 
USG Abdomen showed hepatosplenomegaly with altered hepatic echotexture, findings suggestive of extrahepatic porto systemic shunt(Abernathy malformation type Ib) with bilateral nephromegaly. 
S.Ammonia levels was 76.3umol/L and there was mild coagulopathy. She was started on Lactulose and Inj Vit K. 
CECT Abdomen showed hepatosplenomegaly, Abernathy malformation(type Ib), bilateral nephromegaly and incidental intussusception involving small bowel loop on left, likely transient. 
As no active intervention was possible with the anatomy of the vessels at present. 
Intussusception was managed with bowel rest and soft diet since the child was asymptomatic. 
Ophthalmology examination did not reveal any uveitis/maculopathy or cataract. 
VEP and BERA were normal. Genetics consultation sought, 
WES was sent and report showed heterozygous mutation in BRAF gene suggestive of CFC syndrome. Blood culture was sterile. IV antibiotics was given for 7 days. Mother and caregivers were counselled about the child’s condition and the need for regular follow up. 

Cardiofaciocutaneous (CFC) syndrome is one of the RASopathies and is a rare genetic disorder is typically characterized unusually sparse, brittle, curly hair; relatively large head (relative macrocephaly); a prominent forehead and abnormal narrowing of the sides of the forehead (bi-temporal narrowing); intellectual disability; failure to thrive; heart defects that are present at birth (congenital) or acquired later; short stature and skin abnormalities. CFC syndrome is a dominant disorder often caused de novo mutations in one of four genes called BRAF, MAP2K1 (MEK1), MAP2K2 (MEK2), and KRAS. Some affected individuals do not have a mutation in one of these genes, suggesting that other genes are also associated with CFC syndrome