Cardiofaciocutaneous syndrome

Alternate names

CFC syndrome; Congenital heart defects characteristic facial appearance ectodermal abnormalities and growth failure; Cardio-facio-cutaneous syndrome

Definition

Cardiofaciocutaneous syndrome is a disorder that affects many parts of the body, particularly the heart (cardio-), facial features (facio-), and the skin and hair (cutaneous). People with this condition also have delayed development and intellectual disability, usually ranging from moderate to severe.

Epidemiology

Cardiofaciocutaneous syndrome is a very rare condition whose incidence is unknown. Researchers estimate that 200 to 300 people worldwide have this condition.

Cause

Cardiofaciocutaneous syndrome can be caused by mutations in several genes. Mutations in the BRAF gene are most common, accounting for 75 to 80 percent of all cases. Another 10 to 15 percent of cases result from mutations in one of two similar genes, MAP2K1 and MAP2K2. Fewer than 5 percent of cases are caused by mutations in the KRAS gene. The BRAF, MAP2K1, MAP2K2, and KRAS genes provide instructions for making proteins that work together to transmit chemical signals from outside the cell to the cell's nucleus. This chemical signaling pathway, known as the RAS/MAPK pathway, is essential for normal development before birth. It helps control the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement, and the self-destruction of cells (apoptosis).

Gene muatations

• Mutations in any of these genes can result in the characteristic features of cardiofaciocutaneous syndrome.
• The protein made from the mutated gene is overactive, which alters tightly regulated chemical signaling during development.
• The altered signaling interferes with the development of many organs and tissues, leading to the signs and symptoms of cardiofaciocutaneous syndrome.
• Some people with the signs and symptoms of cardiofaciocutaneous syndrome do not have an identified mutation in the BRAF, MAP2K1, MAP2K2, or KRAS gene.
• In these cases, affected individuals may actually have Costello syndrome or Noonan syndrome, which are also caused by mutations in genes involved in RAS/MAPK signaling.
• The proteins produced from these genes are all part of the same chemical signaling pathway, which helps explain why mutations in different genes can cause conditions with such similar signs and symptoms.
• The group of related conditions that includes cardiofaciocutaneous syndrome, Costello syndrome, and Noonan syndrome is often called the RASopathies.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

Cardiofaciocutaneous syndrome is considered to be an autosomal dominant condition, which means one copy of an altered gene in each cell is sufficient to cause the disorder. Cardiofaciocutaneous syndrome usually results from new gene mutations and occurs in people with no history of the disorder in their family. In a few reported cases, an affected person has inherited the condition from an affected parent.

Signs and symptoms

• People with this condition also have developmental delay and intellectual disability, usually ranging from moderate to severe.
• The signs and symptoms of CFC syndrome overlap significantly with those of two other conditions, Costello syndrome and Noonan syndrome.
• These syndromes belong to a group of related conditions called the RASopathies, which are distinguished by their genetic causes and specific pattern of features.
• It can sometimes be hard to tell these conditions apart in infancy.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Abnormal heart valve morphology
• Abnormality of vision(Abnormality of sight)
• Anteverted nares(Nasal tip, upturned)
• Aplasia/Hypoplasia of the eyebrow(Absence of eyebrow)
• Atrial septal defect(Hole in heart wall separating two upper heart chambers)
• Brittle hair
• Coarse facial features(Coarse facial appearance)
• Dry skin
• Excessive wrinkled skin
• Failure to thrive in infancy(Faltering weight in infancy)
• Feeding difficulties in infancy
• Fine hair(Fine hair shaft)
• Full cheeks(Apple cheeks)
• Global developmental delay
• Intellectual disability(Mental retardation)
• Long face(Elongation of face)
• Long palpebral fissure(Broad opening between the eyelids)
• Muscular hypotonia(Low or weak muscle tone)
• Palmoplantar keratoderma(Thickening of palms and soles)
• Pulmonic stenosis(Narrowing of pulmonic valve)
• Short stature(Decreased body height)
• Thickened helices
• Underdeveloped supraorbital ridges(Flattened bony protrusion above eyes)

30%-79% of people have these symptoms

• Abnormality of the ulna
• Biparietal narrowing
• Cavernous hemangioma(Collection of dilated blood vessels that forms mass)
• Cryptorchidism(Undescended testes)
• Deep palmar crease(Deep palm line)
• Depressed nasal bridge(Flat nasal bridge)
• Downslanted palpebral fissures(Downward slanting of the opening between the eyelids)
• Dystrophic fingernails(Poor fingernail formation)
• EEG abnormality
• Epicanthus(Eye folds)
• Frontal bossing
• Generalized hyperpigmentation
• High forehead
• High palate(Elevated palate)
• Hyperextensible skin(Hyperelastic skin)
• Hypertelorism(Widely spaced eyes)
• Hypoplasia of the zygomatic bone(Cheekbone underdevelopment)
• Ichthyosis
• Long philtrum
• Low posterior hairline(Low hairline at back of neck)
• Low-set, posteriorly rotated ears
• Macrocephaly(Large head)
• Macrotia(Large ears)
• Multiple cafe-au-lait spots
• Multiple lentigines
• Myopia(Close sighted)
• Nystagmus(Involuntary, rapid, rhythmic eye movements)
• Pectus excavatum(Funnel chest)
• Premature birth(Premature delivery of affected infants)
• Ptosis(Drooping upper eyelid)
• Scoliosis
• Short neck(Decreased length of neck)
• Short nose(Decreased length of nose)
• Slow-growing hair(Slow growing hair)
• Sparse hair
• Sparse or absent eyelashes
• Strabismus(Squint eyes)
• Webbed neck(Neck webbing)

Diagnosis

The diagnosis of CFC syndrome is suspected by clinical findings and confirmed on molecular genetic testing.[1].

Treatment

• Care by a multidisciplinary team
• Management of cardiac structural defects, hypertrophic cardiomyopathy, and arrhythmias as in the general population
• Increased ambient humidity or hydrating lotions for xerosis and pruritus I
• Increased caloric intake and a nasogastric tube or gastrostomy for severe feeding problems
• Surgical intervention for severe gastroesophageal reflux
• Routine management of growth hormone deficiency, ocular abnormalities
• Management of seizures may require polytherapy
• Occupational therapy
• Physical therapy, and speech therapy as needed.
• Consensus medical management guidelines have been published.[2].

NIH genetic and rare disease info

• NIH info on Cardiofaciocutaneous syndrome

Cardiofaciocutaneous syndrome is a rare disease.

Cardiofaciocutaneous syndrome Resources
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