Systematic ophthalmologic evaluation in cardio-facio-cutaneous syndrome: A genotype-endophenotype correlation

Area of Science:

• Genetics
• Ophthalmology
• Developmental Biology

Background:

• Cardio-facio-cutaneous syndrome (CFCS) is a rare genetic disorder within the RASopathies, characterized by upregulated RAS/MAPK signaling.
• Key clinical features include distinctive facial features, ectodermal and cardiac anomalies, growth deficits, intellectual disability, and musculoskeletal issues.
• Ocular abnormalities like visual impairment and refractive errors are anecdotally reported in CFCS patients.

Purpose of the Study:

• To determine the prevalence of ophthalmologic abnormalities in a large cohort of individuals with CFCS.
• To investigate potential genotype-endophenotype correlations related to ocular findings in CFCS.

Main Methods:

• Retrospective analysis of ophthalmologic data from a monocentric cohort of CFCS patients.
• Correlation of specific gene mutations (KRAS, BRAF, MAP2K1, MAP2K2) with observed ophthalmologic phenotypes.

Main Results:

• BRAF mutations were linked to higher rates of anisometropia (>3D) and high astigmatism.
• Mutations in other CFCS-associated genes correlated with a higher prevalence of high myopia (>6D).
• Pale optic discs were associated with inferior oblique muscle overaction and less frequently with ptosis, often co-occurring with exotropia and nystagmus.

Conclusions:

• CFCS patients exhibit a significant prevalence of ophthalmologic abnormalities, necessitating thorough eye evaluations.
• Specific genotypes correlate with distinct ocular findings, aiding in risk stratification.
• Earlier ophthalmologic referral is crucial for CFCS patients, especially those with BRAF mutations, to mitigate the risk of amblyopia.