cardiofaciocutaneous syndrome 3

Cardiofaciocutaneous syndrome 3 (CFC3) is a multisystem condition that affects the heart, facial appearance, skin, and skeleton. It results from changes in the MAP2K1 gene, which encodes a signaling protein involved in cell growth and development. Features usually become apparent in infancy or early childhood, but the exact age of diagnosis can vary. Because published case numbers are small, the true frequency in the population is not well established. Severity and symptoms vary widely between individuals.

Several findings are considered characteristic of CFC3. Nearly all affected individuals have distinctive curly hair, increased sweating, thickened patches of skin known as hyperkeratosis, and difficulty tolerating heat. A sunken chest wall (pectus excavatum) and low muscle tone (hypotonia) are also consistently reported and often prompt early medical attention. Neurological features can include developmental delays related to hypotonia and, in some children, seizures. As children grow, orthopedic issues such as scoliosis or reduced bone mineral density may emerge and benefit from ongoing monitoring. Not all individuals experience all features, and the type and severity of manifestations can change over time.

CFC3 is caused by pathogenic variants in the MAP2K1 gene. MAP2K1 produces a protein kinase that helps relay signals within cells, guiding how tissues grow, differentiate, and respond to external cues. Disruption of this signaling pathway alters development in multiple organ systems, leading to the blend of cardiac, craniofacial, cutaneous, and skeletal findings seen in the syndrome. The condition follows an autosomal dominant inheritance pattern, meaning a single altered copy of MAP2K1 is sufficient to cause disease. An affected individual has a 50 percent chance of passing the variant to each child, while parents who do not carry the variant have a very low likelihood of having another affected child. Genetic counseling is recommended for families to understand testing options and reproductive considerations.

Currently, management focuses on supportive care tailored to each person’s needs, and there are no therapies specifically approved for CFC3. A multidisciplinary team approach is important, often involving cardiology, neurology, dermatology, orthopedics, physical and occupational therapy, and genetics specialists. Seizures, when present, are treated with standard antiseizure medications chosen by a neurologist. Physical therapy can help address hypotonia and improve motor development, while dermatologic treatments may relieve skin discomfort caused by hyperkeratosis or excessive sweating. Regular surveillance is an essential part of long-term care, with periodic evaluations for cardiac health, spinal alignment, bone density, and developmental progress so that emerging complications are detected early and managed promptly. Families should work closely with their healthcare team to determine an individualized monitoring schedule and to explore supportive resources.

Long-term outcomes for individuals with CFC3 range from mild to significant medical and developmental challenges. Many children achieve important developmental milestones with appropriate therapies, although some may require ongoing support into adulthood. Potential complications such as progressive scoliosis or refractory seizures can influence overall health, underscoring the value of consistent follow-up. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with expert centers and genetic counselors who can coordinate care, provide up-to-date information, and facilitate access to community and educational resources.