Neurofibromatosis Type 1 – Symptoms and Causes
Overview
Neurofibromatosis type 1 (NF1) is a rare genetic disorder affecting about 1 in 2,500 people. It causes distinctive skin changes and nerve tissue tumors.
People with NF1 often develop light brown spots on their skin and freckles in the armpits and groin areas.
The condition can cause tumors to grow on nerves throughout the body, including the brain and spinal cord. Most of these tumors are benign (non-cancerous), but they can sometimes become malignant.
Many people experience mild symptoms, but NF1 can lead to various complications.
Common complications include:
- Learning difficulties
- Heart and blood vessel problems
- Vision impairment
- Chronic pain
Treatment for NF1 typically focuses on:
- Supporting healthy development in children
- Managing complications early
- Surgical removal of problematic tumors
- Medication therapy
Medical advances have brought new treatment options, including a recently approved medication for children with NF1-related tumors. Research continues to develop additional treatments for this condition.
Signs and Symptoms
People with neurofibromatosis type 1 (NF1) usually show signs early in life. Most symptoms appear by age 10, with many present at birth or shortly after.
The severity varies from person to person, but symptoms are typically mild to moderate.
Common signs include light brown spots on the skin called cafe au lait spots. Having more than six of these spots may suggest NF1.
These harmless marks often appear at birth or during early childhood, and new spots stop developing after childhood.
Freckle clusters in the armpits or groin area typically develop between ages 3 and 5. These freckles are smaller than cafe au lait spots and gather in skin folds.
Small bumps called Lisch nodules may form on the iris (colored part of the eye). These don’t harm vision and are hard to see without special equipment.
Skin Growths
- Soft, pea-sized bumps (neurofibromas) on or under the skin
- Plexiform neurofibromas that involve multiple nerves
- Facial growths that may cause disfigurement
- Number of growths may increase with age
Bone development can be affected, leading to irregular formation, curved spine (scoliosis), or bowed lower legs. People with NF1 often have low bone mineral density.
Children with NF1 might develop optic pathway gliomasโtumors on the nerve connecting the eye to the brain. These typically appear by age 3 and rarely develop in teenagers or adults.
Learning difficulties are common with NF1. Children may have specific learning disabilities affecting reading or math skills. ADHD and delayed speech development also frequently occur alongside NF1.
Physical characteristics often include a larger than average head size due to increased brain volume and below-average height.
When to Seek Medical Help
Contact a healthcare provider if you notice signs of NF1 in your child.
While most tumors associated with this condition grow slowly and aren’t cancerous, early diagnosis allows for better management of complications. Medical treatments are available for certain types of growths, including plexiform neurofibromas.
Regular checkups help monitor the condition and address any new developments promptly.
Causes
Neurofibromatosis type 1 stems from changes in the NF1 gene found on chromosome 17. This genetic alteration can be:
- Inherited from a parent
- Formed during early development (spontaneous mutation)
The NF1 gene normally makes neurofibromin, a protein that helps control cell growth. When the gene changes, the body produces less neurofibromin or none at all.
This lack of regulation allows cells to grow uncontrollably, leading to tumors and other features of the condition.
Risk Factors
The main risk factor for neurofibromatosis type 1 (NF1) is family history. About 50% of NF1 cases are inherited from a parent who has the condition.
The other half of cases come from new genetic changes with no family history of the disease.
NF1 follows an autosomal dominant inheritance pattern. This means:
- Only one parent needs to have the altered gene to pass it on
- Each child of an affected parent has a 50% chance of inheriting NF1
- The condition affects males and females equally
People with no family history of NF1 who develop the condition typically have a new genetic mutation that occurred spontaneously.
Complications
NF1 complications can vary greatly among individuals, even within families. Problems often arise when tumors affect nerves or press against organs.
People with NF1 may experience learning difficulties or cognitive challenges as common neurological issues. Less frequently, they might develop epilepsy or excess fluid in the brain.
The visible signs of NF1 can impact self-esteem. Brown spots on the skin and multiple facial tumors might cause emotional distress for some patients, even when these symptoms don’t pose serious health risks.
Bone-related problems include leg bowing and fractures that heal poorly. Scoliosis (spine curvature) may require braces or surgery. People with NF1 also have lower bone density, increasing their osteoporosis risk.
Vision changes can occur if tumors called optic pathway gliomas develop on the optic nerve. These growths can interfere with normal sight.
During hormonal changes like puberty or pregnancy, symptoms may worsen with more neurofibromas appearing. Most pregnancies proceed normally for NF1 patients, but specialist monitoring is recommended.
Heart and blood vessel issues are more common in NF1 patients, including high blood pressure and vascular conditions.
In rare cases, breathing difficulties happen when tumors press on airways.
Cancer risk increases with NF1. Tumors can become malignant, particularly those under the skin or plexiform neurofibromas. Other cancers occur more frequently in NF1 patients:
| Cancer Type | Notes |
|---|---|
| Breast cancer | Screening should start at age 30 (earlier than general population) |
| Leukemia | Blood cancer |
| Colorectal cancer | Intestinal cancer |
| Brain tumors | Various types |
| Soft tissue cancers | Several varieties |
Noncancerous tumors of the adrenal gland called pheochromocytomas can develop. These growths release hormones that raise blood pressure and typically require surgical removal.
