An Unusual Presentation of Cardiofaciocutaneous Syndrome Diagnosed Through Whole Genome Sequencing: A Case Report

Cardiofaciocutaneous syndrome is a rare, sporadic disease caused by germline mutations in the Ras/MAPK (mitogen-activated protein kinase) pathway. Patients usually present with craniofacial anomalies, cardiac defects, and neurocutaneous abnormalities. The features of cardiofaciocutaneous syndrome overlap with two other syndromes known as Noonan’s syndrome and Costello’s syndrome. Similarly, those two syndromes are caused by mutations in the Ras/MAPK pathway. The diagnosis of cardiofaciocutaneous syndrome is suspected based on the clinical presentation and confirmed by genetic analysis. We report a case of a seven-month-old boy who presented with complaints of developmental delay, poor weight gain, and seizures. Physical examination revealed several dysmorphic features, including coarse facies, long philtrum, thin upper lip, a broad forehead, and long toes. Neurological examination showed hypotonia in all four limbs, with normal power and reflexes. However, the infant did not have any remarkable cutaneous abnormalities. Whole-exome sequencing picked up a BRAF gene mutation, and the patient was diagnosed with cardiofaciocutaneous syndrome. On follow-up, the patient developed findings suggestive of autoimmune hepatitis. Cardiofaciocutaneous syndrome remains a challenging diagnosis that requires a detailed assessment of the patient, as well as qualified centers with genetic analysis for diagnosis confirmation. Management of cardiofaciocutaneous patients requires a multidisciplinary team approach in order to improve the outcomes. Further exploration is required into atypical presentations of the disease as well as autoimmune disease associated with RASopathies.