Overview

Cardiofaciocutaneous syndrome (CFCS)  is a congenital condition characterised by dysmorphic craniofacial (face and skull) traits, cardiac issues, skin and hair irregularities, eye abnormalities, hypotonia, gastrointestinal dysfunction, seizures and varying degrees of neurocognitive delay.¹ Additionally, there could be fast-growing or dystrophic brittle nails and sparse hair. Many individuals suffer from poor growth as a result of hypotonia (decreased muscle tone) and gastrointestinal dysfunction. The gastrointestinal challenges require a nasogastric tube for feeding during the neonatal period.² Good nutrition and gastrointestinal care are essential for a better lived experience for people with CFCS. Caregivers and healthcare professionals must understand the feeding and digestive challenges associated with the condition. Adequate care strategies must be provided. Therefore, this article aims to provide a concise and useful summary of the dietary and gastrointestinal requirements of people with CFCS.

Understanding cardiofaciocutaneous syndrome

CFCS is a multisystematic disorder affecting 1 in 800,000 newborns.³ CFCS belongs to a group of syndromes known as “RASopathies”, which are caused by germline mutations in one of the genes encoding components of the RAS-MAPK signal induction pathway. RAS-MAPK is a pathway that plays a role in the normal cellular processes, including cell growth, proliferation, survival, differentiation, metabolism, and migration.³ The pathway is composed of the RAS proteins, RAS guanine nucleotide exchange factors (GEFs), RAS GTPase-activating proteins (GAPs), RAS effector proteins and their targets, and other pathway modulators.⁴ CFC syndrome is a rare RASopathy inherited in an autosomal-dominant manner and is caused by germline pathogenic variants in BRAF (75%), MAP2K1 (which encodes MEK1), and MAP2K2 (which encodes MEK2) or KRAS.⁴ People with CFC syndrome have congenital (present from birth) cardiac anomalies, fine, curly, and fragile hair, sparse eyebrows and eyelashes, hyperkeratotic (thickened) skin, and frequent hemangiomas (non-cancerous tumours).⁴ People with CFC syndrome have small stature and failure to thrive due to oral aversion and gastrointestinal reflux.

Nutritional challenges in cardiofaciocutaneous syndrome

CFC syndrome patients could encounter considerable nutritional problems, particularly during early life. Feeding and eating challenges are prevalent issues in individuals with CFC syndrome and are some of the first challenges a caregiver could face when trying to address a CFC diagnosis. Hypersensitivity of the oral cavity can make the introduction of solid foods difficult. From a gastrointestinal perspective, gastroesophageal reflux disease (GERD), recurrent vomiting, nausea, and aerophagia (excessive swallowing of air) have been documented in both infant and adult CFC syndrome patients.⁵ Delayed gastric emptying can further complicate this. In the most severe instances, these conditions necessitate artificial internal nutrition through either a nasogastric tube or, more rarely, a gastrostomy tubes.⁵ 

Intestinal dysmotility-related constipation could occur during infancy and persist throughout life, irrespective of genetics.⁵ Puberty could be delayed in individuals with CFCS. Many patients of CFCS suffer from hypotonia.² Hypotonia causes a decrease in muscle tone, which affects the strength and coordination of muscles used for sucking, chewing and swallowing. Infants often struggle with breastfeeding or bottle feeding due to weak motor control. The overall inability to feed effectively leads to development issues and failure to thrive. It's important that patients suffering from CFCS are given adequate treatment to promote good nutrition and growth. 

Nutritional assessment and management strategies

Correct assessments and monitoring of CFCS patients are important to establish the extent of the disease; this will allow a tailored treatment plan for each individual. A complete physical exam with precise measurements of growth parameters is required, including the weight, height and head circumference. When monitoring for GERD,  the risk of aspiration (food or liquid entering the airway) should be evaluated, and a swallowing study conducted.¹ It is important to note the possibility of intestinal malrotation (intestines do not rotate during fetal development) and check for signs of constipation.¹ Additionally, a nutritional intake evaluation should be conducted. 

In CFCS, failure to thrive and inadequate growth throughout infancy are prevalent. The swallowing difficulties are reflected early by prenatal polyhydramnios (too much amniotic fluid surrounding the baby in the womb);⁶ this subsequently leads to challenges in sustaining adequate calorie intake postnatally. Treatment can include prolonged supplemental feedings via nasogastric tube feedings or gastrostomy tube placement. These treatments are fairly common, amounting to (40% to 50%).⁶ Many CFCS patients still require assistance in feeding towards their late childhood. Feeding therapy is something that should be conducted at the first signs of oral aversion. Proton pump inhibitors could treat gastrointestinal reflux in CFCS patients.⁶

Different feeding techniques can be used for infants and children. Children with gastrointestinal reflux are increasingly being treated with thickened feeds.⁷ Thickened feeds have been driven largely by the baby food industry. Studies show that although thickened formulas don’t seem to reduce measurable reflux, they may reduce vomiting.⁷ Trophic feeding (enteral nutrition) is a practice commonly used for infants with congenital heart disease.⁷ Although this feeding method can be used to support the feeding difficulties of a CFCS patient. It involves giving very small volumes of milk or formula to infants in order to stimulate the infant's immature digestive system; this prepares the infant's body for full enteral feeding. It could be beneficial to gradually increase enteral feeds in infants up to 40-60 ml/kg/day.⁷             

Role of a multidisciplinary care team

There is no cure for CFC syndrome. However, supportive care can maximise quality of life, improve function, and reduce complications. Other benefits of multidisciplinary care teams include improved health outcomes, enhanced patient satisfaction, and increased efficiency in service delivery. A multidisciplinary team ensures that every aspect of a child's health and well-being is addressed by specialists in relevant fields. Paediatricians will be required for the patient's overall medical management, including growth monitoring, development, seizures, vision, and cardiac status.¹ For patients with delayed development, occupational and speech therapists are recommended for evaluation of swallowing, feeding, and oral motor issues.⁸ Registered dietitians are recommended to support nutritional adjustments when feeding difficulties arise. Geneticists are essential for diagnosis, family counseling, and family education. A cardiologist would be expected to conduct standard treatments for cardiovascular defects. Additionally, it could be beneficial for CFCS patients to regularly be seen by an endocrinologist to manage hormones or delayed puberty.¹ Aside from the specialists, families should be involved in the planning and implementation of their children's care. Families can offer vital information about a child's different needs and strengths to create a nurturing environment where families receive medical management education; this covers the use of care equipment and practices. 

Summary

Cardiofactiocauteus syndrome is a condition in which patients show multiple congenital anomalies. It is characterised by dysmorphic craniofacial features, cardiac issues, skin and hair abnormalities, eye abnormalities, hypotonia, gastrointestinal dysfunction, seizures, and different degrees of neurocognitive delay.¹ A germline mutation in one of the genes within the  RAS-MAPK pathway causes the condition; this pathway is responsible for normal cellular processes within the body, such as cell growth and proliferation.

Patients with CFC syndrome frequently experience complex nutritional and gastrointestinal challenges beginning in early childhood. Some of these challenges include gastroesophageal reflux (GERD), constipation, delayed gastric emptying, and poor oral motor skills. The inability to feed adequately leads to poor growth and development. Many CFCS patients, particularly children, require specialised treatment strategies in order to feed adequately; this includes different feeding techniques such as “thickened feeds” or trophic feeding for infants. To guarantee proper nutrition in more difficult situations, enteral feeding via a nasogastric tube might be necessary.

Management of these complications involves help from a multidisciplinary team, including paediatricians, registered dietitians, geneticists, cardiologists, and speech and occupational therapists. Furthermore, dietary interventions could relieve constipation. The early and ongoing engagement of this care team, together with family and educational support, is crucial for addressing feeding challenges, enhancing growth, and improving the quality of life for individuals with CFC syndrome.