Dermatological manifestations, management, and care in RASopathies

Area of Science:

• Genetics
• Dermatology
• Molecular Biology

Background:

• RASopathies are a group of rare genetic disorders stemming from pathogenic variants in the RAS/MAPK signaling pathway.
• This pathway is crucial for regulating cell proliferation, differentiation, survival, and death.
• Dysfunction leads to syndromes with overlapping clinical features, notably skin and adnexal lesions.

Purpose of the Study:

• To highlight the dermatological diagnosis, management, and care of non-NF1 RASopathies.
• To emphasize the role of skin manifestations in the differential diagnosis of RASopathies.
• To provide an overview of the less-known RASopathies beyond neurofibromatosis type 1 (NF1).

Main Methods:

• Review of clinical features and diagnostic criteria for non-NF1 RASopathies.
• Analysis of dermatological manifestations including pigmented lesions, hyperkeratosis, and hyperplasia.
• Focus on differential diagnosis based on skin findings.

Main Results:

• Dermatological signs are key diagnostic indicators for differentiating between various RASopathies.
• Manifestations include pigmented lesions (nevi, lentigines, café-au-lait spots), hyperkeratosis (keratosis pilaris, palmoplantar keratosis), and hyperplasia.
• While malignancy links are rare, skin lesions significantly impact patient quality of life.

Conclusions:

• Dermatological assessment is critical for the early and accurate diagnosis of non-NF1 RASopathies.
• Understanding diverse skin manifestations aids in distinguishing between these complex genetic disorders.
• Management should address skin lesions to improve the quality of life for affected individuals.