Exploring the clinical complexity of cardio-facio-cutaneous syndrome: insights from a pediatric case series.

BACKGROUND

Cardio-Facio-Cutaneous syndrome (CFCS) is a rare autosomal dominant genetic disorder primarily caused by BRAF gene mutations, posing diagnostic challenges due to its multifaceted clinical presentation.

OBJECTIVE

To elucidate the clinical characteristics of pediatric CFCS patients, expanding the phenotypic spectrum to enhance early diagnostic capabilities, while also presenting the relationship between genotye and corresponding phenotype severity.

METHODS

From January 2015 to March 2022, four children diagnosed with CFCS in Children's Hospital of Chongqing Medical University were included for analysis. Whole exome sequencing (WES) was conducted to identify the types and locations of possible gene mutations. Neurological development was assessed using electroencephalography (EEG), magnetic resonance imaging (MRI) and Gesell developmental evaluation.

RESULTS

All four CFCS patients exhibited gene mutations, manifesting with cardiac malformations, distinctive facial features, skin and hair changes, and neurological abnormalities. WES revealed that the specific mutations were closely linked to their clinical severity. Three patients displayed milder symptoms (case 1-3, genotype I or II), demonstrating stability or slight improvement, whereas one patient (case 4, genotype III) suffered from a severe phenotype characterized by profound neurological and digestive system impairments, leading to a significantly reduced quality of life and a grim prognosis.

CONCLUSION

In CFCS patients, severe developmental delay and seizures are predominant neurological features, possibly accompanied by continuous spike-and-wave during sleep (CSWS) and severe sleep disturbances. CFCS generally carries a poor prognosis, underscoring the importance of disease awareness and early genetic testing.