What is the prevalence of neurofibromatosis (NF) in the Philippines?

Prevalence of Neurofibromatosis in the Philippines

Neurofibromatosis type 1 (NF1) affects approximately 1 in 3,000 individuals worldwide, making it one of the most common genetic disorders globally, though specific prevalence data for the Philippines is not available. 1

Epidemiology of Neurofibromatosis

• NF1 is the most common type of neurofibromatosis, affecting 1 in 2,000-3,000 people worldwide, with no known variation in prevalence specific to the Philippines 1
• NF2 is much rarer, affecting approximately 1 in 25,000-33,000 individuals globally 1, 2
• Both conditions are autosomal dominant disorders, with about 50% of cases being new mutations (sporadic cases) and 50% being inherited from an affected parent 3
• There is no documented ethnic or geographical variation in NF1 prevalence that would suggest a different rate in the Philippines compared to global statistics 1

Types of Neurofibromatosis

Neurofibromatosis Type 1 (NF1)

• Caused by mutations in the NF1 gene on chromosome 17, which encodes neurofibromin, a negative regulator of the RAS-MAPK pathway 2
• Characterized by café-au-lait macules, neurofibromas, intertriginous freckling, and Lisch nodules 4
• Optic pathway gliomas occur in 15-20% of NF1 patients, typically in young children 1
• Plexiform neurofibromas are often congenital but grow during the first two decades of life 2

Neurofibromatosis Type 2 (NF2)

• Caused by mutations in the NF2 gene on chromosome 22, which encodes merlin (schwannomin) 2
• Defined by bilateral vestibular schwannomas on the eighth cranial nerves 2, 1
• Multiple meningiomas and other central nervous system tumors are common features 2

Clinical Impact and Mortality

• NF1 is associated with an 8-15 year reduction in average life expectancy, primarily due to malignant neoplasms and cardiovascular causes 1
• The risk of malignant peripheral nerve sheath tumors (MPNST) in NF1 patients is 8.5% by age 30,12.3% by age 50, and 15.8% by age 85 1, 5
• High-grade MPNSTs are usually fatal and contribute significantly to NF1 mortality 1, 5
• Chronic pain is a common but underrecognized problem in NF1 patients 6

Diagnostic Approach

• The American College of Medical Genetics and Genomics recommends evaluation by and care coordination with a specialized NF clinic 5
• Diagnosis is primarily clinical, based on established criteria including café-au-lait macules, neurofibromas, and other characteristic findings 4
• Genetic testing can confirm diagnosis in uncertain cases 1

Management Recommendations

• Annual general medical evaluation is recommended, including assessment for signs of MPNST, pheochromocytoma, neuropathy, depression, and chronic pain 5
• Women with NF1 should begin annual mammograms at age 30 and consider breast MRI with contrast between ages 30-50 5
• Baseline MRI of known or suspected non-superficial plexiform neurofibromas should be considered 5
• Pregnant women with NF1 should be referred to a high-risk obstetrician 5

Clinical Pitfalls and Special Considerations

• NF1 is often progressive, with new manifestations appearing over time 4
• The condition shows extreme variability in expression, even within families 4
• NF1 should not be underestimated as a "mere cosmetic problem" due to the increased risk of malignant tumors 3
• Metabolic bone disease is common; many patients are frankly osteopenic, which complicates treatment of orthopedic manifestations 7