What is Cardiofaciocutaneous Syndrome (CFC)?
CFC syndrome is a rare genetic condition that typically affects the heart (cardio-), facial features (facio-) and skin (cutaneous). It is seen with equal frequency in males and females and across all ethnic groups. Children with CFC syndrome may have certain features that suggest the diagnosis, such as relatively large head size, down-slanting eyes, sparse eyebrows, curly hair, areas of thickened or scaly skin, and small stature. Most will also have a heart defect.
While there is a wide spectrum of severity in CFC syndrome, most individuals will have some degree of learning difficulty and developmental delay. There are several characteristic facial features that are evident in CFC syndrome that may overlap with other conditions, particularly Noonan Syndrome (NS) and Costello Syndrome (CS). Therefore, accurate diagnosis is essential for proper medical management.
How common is CFC?
There are over 100 individuals reported in the literature. It is estimated that there are perhaps 200-300 individuals worldwide.
What are the features of the condition?
There are a wide range of features of CFC syndrome including:
Craniofacial features
Large forehead, relative macrocephaly (large head), bitemporal narrowing, down-slanting palpebral fissures (eyes) with epicanthic folds, ptosis (droopy eyelid), depressed nasal bridge, posteriorly rotated ears, high arched palate.
Heart Defects
Pulmonic stenosis, atrial septal defects, ventricular septal defects, hypertrophic cardiomyopathy, heart valve anomalies and rhythm disturbances. These defects may be identified at birth or diagnosed later by the presence of a heart murmur. Some individuals may have normal hearts.
Ectodermal manifestations
SKIN: Dry, hyperkeratotic (thickened), ichthyotic (scaly), keratosis pilaris (small, goose flesh), eczema (extreme dryness of skin and itchiness), hemangiomas, café-au-lait spots (flat, dark spots), erythema (redness to the skin), moles (very dark freckles).
HAIR: sparse, curly, fine or thick, wooly or brittle hair; eyelashes and eyebrows may be absent or normal.
NAILS: nail dystrophy and/or flat broad nails.
Ocular findings
Most common eye findings are hypertelorism (wide spaced eyes), strabismus, nystagmus, astigmatism, myopia, hyperopia, optic nerve hypoplasia, cortical blindness and cataracts. Individuals may also have epicanthal folds and ptosis. Any combination of these features might result in decreased vision and acuity. Rare individuals may not have ocular abnormalities.
Feeding/Gastrointestinal (GI) problems
Severe feeding problems may be associated with gastroesophageal reflux, vomiting, oral aversion; intestinal malrotation, hernia and constipation. Most individuals have failure to thrive.
Growth delays
The feeding problems play a significant role in their growth retardation. Growth failure may manifest as normal birth weight and length, but during early infancy weight and length may drop to below the 5th percentile while head size remains on the growth curve (relative macrocephaly). Some individuals may have growth hormone deficiency.
Neurologic findings
Hypotonia (low muscle tone), seizure disorders, abnormal EEG (slow and dysrrhythmic), hydrocephalus, cortical atrophy, ventriculomegaly, frontal lobe hypoplasia, agenesis of the corpus callosum, Chiari malformation, pachygyria, microcephaly, cognitive impairment (ranging from mild to severe).
Management of the child with CFC syndrome should include the following evaluations:
- Neurologic evaluation
- MRI of the brain to detect any structural changes of the brain
- Electroencephalogram (EEG) if seizures are suspected
- Growth and psychomotor developmental monitoring
- Endocrine evaluation for short stature
- Regular ophthalmology (eye) examinations
- Regular audiologic (hearing) examinations
- Regular cardiac (heart) evaluations
- Nutrition and feeding evaluation
- Enrollment in early intervention therapies to promote growth, motor, and intellectual development – such as occupational therapy (OT), physical therapy (PT), or speech therapy.
- Health care team (individual treated based on symptoms)
What causes CFC?
CFC syndrome is caused by a mutation (change) in one of our genes. Genes are the instructions which tell our body how to develop and function properly. If there is a change in one of our genes, it can affect how the gene is supposed to function and how the body develops.
Recently, three different genes have been found to be associated with CFC syndrome (BRAF, MEK1, MEK2). Most individuals with CFC syndrome (87%) have a mutation in the BRAF gene and 13% have a mutation in MEK1/2. Molecular genetic (DNA) testing for mutations in all of these genes is clinically available.
How is it diagnosed?
In the past, the diagnosis of CFC was based on the clinical features, medical, and developmental history of the child. However with the recent discovery of genes that cause CFC, we are now able to offer genetic testing for any individual suspected of having the diagnosis. There are still some individuals with CFC syndrome who do not have a mutation in one of these genes, which suggests that there may be other genes associated with CFC syndrome that have not yet been identified.
What are the chances of having another child with CFC?
All cases of CFC syndrome have been sporadic, meaning that only one person in the family has CFC syndrome. As of yet, there have been no documented cases of CFC syndrome occurring in siblings or of a parent passing CFC on to a child. If neither parent has CFC syndrome nor a mutation in one of the genes, then the chance of having another child with CFC syndrome is very low (
Currently, there is no cure to treat all of the symptoms of CFC syndrome. However, with proper management and early intervention, much can be done to improve the health of children with CFC syndrome. At present, treatment ultimately depends on the unique characteristics of each individual. These can include heart surgery to repair a structural defect, medications and lotions for the skin problems, or eye surgeries or corrective lenses to improve vision.
Source: cfcsyndrome.org