Cardiofaciocutaneous syndrome – a longitudinal study of a case over 33 years: case report and review of the literature

Abstract

Cardiofaciocutaneous (CFC) syndrome [Online Mendelian Inheritance in Man (OMIM) #115150] is characterized by craniofacial dysmorphism, heart malformation, ectodermal abnormalities, neuromotor delay and intellectual disability. It is not a frequent disease, about 300 cases have been reported in the medical literature. We describe the case of a 34-year-old patient presenting with CFC syndrome phenotype, monitored since the age of 1 1/2 years. Clinical findings included craniofacial dysmorphism, development delay, heart malformation and severe intellectual disability. The evolution was with progressive intellectual disability, hypogonadism, hypertrophic cardiomyopathy, wrinkled palms and soles. Molecular analysis showed a heterozygous variant in the B-Raf proto-oncogene, serine/threonine kinase (BRAF) gene (7q34): NM_001354609.2:c.1502A>G, with pathogenic significance. We report this case, observed along a period of 33 years, for illustration of clinical evolutive particularities, and for difficulties in establishing the positive diagnosis.

"A Rare Presentation of Multiple Eruptive Melanocytic Nevi in a Pediatric Patient with Cardiofaciocutaneous Syndrome Type 4"

“…This pathway is composed of proteins that govern cell differentiation, proliferation, migration, and apoptosis. Mutations in this pathway can lead to dysregulation of these processes, resulting in uncontrolled cell proliferation and ultimately cancer [1][2][3][4][5]9]. CFC is caused by germline mutations along the Ras/MAPK cell signaling pathway.…”

“…Similarly, to Noonan Syndrome, and others, it's considered one the RASopathies, with germline mutations along the Ras/MAPK cell signaling pathway. This signaling pathway is involved in the regulation of cell differentiation, proliferation, migration, and apoptosis [1][2][3][4][5]. Its phenotypic diversity can take on a multitude of forms, with patients exhibiting a subset or all of the traits; hence, not all of the physical findings must be present for a diagnosis.…”

“…Approximately 300 cases have been described in the literature. 5 In addition, the reported prevalence in Japan is 1/810,000 people [2].…”

Analysis of the Oral Microbiome in a Patient with Cardiofaciocutaneous Syndrome and Severe Periodontal Disease: Impact of Systemic Antibiotic Therapy

“…In the context of RASopathies, CFCS has several manifestations that can determine its dental management such as heart defects, seizures, and intellectual disability. Although this patient presented no congenital heart disease, heart problems in certain cases can appear later (e.g., hypertrophic cardiomyopathy) [ 24 ]. Neurodevelopment disorders and particularly intellectual disabilities have a prevalence greater than 80% among patients with CFCS [ 25 ], which can limit, as in the present case, the patient’s level of cooperation in the dental setting.…”

Exome sequencing in a child with neurodevelopmental disorder and epilepsy: Variant analysis of the AHNAK2 gene

“…It is a very rare syndrome and only 300 cases are reported in the literature but the real incidence is still unidentified probably because mildly affected individuals may go undiagnosed. All known cases are due to autosomal dominant mutations in four different genes: BRAF (7q34) is present in about 75% of cases, MEK1 (15q22.1‐q22.33) and MEK2 (19p13.3) are both present in about 25% of the cases, and KRAS (12p12.1) is present in less than 2% of the cases, all these genes are implicated in KRAS signaling pathways (Jurcă et al, 2021 ).…”