Phakomatoses: Overview
Phakomatoses are a group of rare genetic disorders that primarily affect tissues derived from the ectoderm, including the skin, eyes, and central nervous system. They are typically caused by mutations in genes involved in cellular growth and proliferation.
Common Types
- Neurofibromatosis Type 1 (NF1): The most common type, characterized by café-au-lait spots, neurofibromas, and other skin and neurological manifestations.
- Neurofibromatosis Type 2 (NF2): Primarily affects the nervous system, causing bilateral vestibular schwannomas, meningiomas, and other tumors.
- Tuberous Sclerosis Complex (TSC): A multisystem disorder that involves the brain, kidneys, skin, and other organs, leading to seizures, kidney cysts, and tumors.
- Sturge-Weber Syndrome: Characterized by a facial "port-wine stain" birthmark, glaucoma, and leptomeningeal angioma (a brain abnormality).
- Von Hippel-Lindau Syndrome (VHL): An autosomal dominant condition causing the development of benign and malignant tumors, including hemangioblastomas in the brain and retina, renal cell carcinomas, and pheochromocytomas.
Genetics
Most phakomatoses are single-gene disorders, inherited in an autosomal dominant, recessive, or X-linked manner. Mosaicism, where only a portion of the body's cells carry the mutation, can lead to variable presentations.
Diagnosis
Established diagnostic criteria exist for several phakomatoses, while genetic testing can confirm a diagnosis in others. However, clinical judgment is crucial due to the possibility of false negatives.
Treatment
Treatment varies depending on the specific phakomatoses. Surveillance is essential to detect new manifestations. Some treatments address underlying genetic causes, such as mTOR inhibitors for TSC.
Multidisciplinary Care
Due to the multisystemic nature of phakomatoses, a multidisciplinary approach to care is preferred. Integrated clinics may include specialists in genetics, neurology, ophthalmology, and other fields to provide comprehensive care over the lifespan.