Introduction to phacomatoses (neurocutaneous disorders) in childhood

Area of Science:

• Genetics and Molecular Biology
• Dermatology
• Neurology
• Ophthalmology

Background:

• Phacomatoses, historically termed neurocutaneous syndromes, are heterogeneous genetic disorders.
• These conditions are characterized by congenital abnormalities primarily affecting the skin, central and peripheral nervous systems, and eyes.
• The historical evolution of terminology reflects a growing understanding of their complex nature and underlying pathogenesis.

Purpose of the Study:

• To provide a comprehensive review of phacomatoses, encompassing their historical context and modern understanding.
• To detail the classification, genomics, clinical manifestations, diagnostic criteria, surveillance, and therapeutic strategies for various phacomatoses.
• To elucidate the molecular pathways implicated in the pathogenesis and phenotypic variability of these disorders.

Main Methods:

• Literature review focusing on the history, classification, genomics, clinical features, diagnostics, surveillance, and therapies of phacomatoses.
• Analysis of historical terminology and proposed classifications.
• Discussion of implicated molecular signaling pathways (e.g., RAS, MAPK/MEK, ERK, mTOR, RHOA, PI3K/AKT, PTEN, GNAQ, GNA11).

Main Results:

• Phacomatoses are classified into groups based on predominant features: tumor predisposition, vascular malformations, vascular tumors, pigmentary/connective tissue mosaicism, dermal dysplasia, and twin spotting.
• Key signaling pathways are identified as crucial in the pathogenesis, explaining phenotypic diversity and overlap.
• The review synthesizes information on diagnosis, management, and surveillance protocols for various phacomatoses.

Conclusions:

• Phacomatoses represent a complex group of genetic disorders with significant clinical heterogeneity.
• Understanding the underlying molecular pathways is essential for accurate diagnosis, targeted therapy, and improved patient outcomes.
• This review provides a framework for current knowledge and future research directions in the field of phacomatoses.