Neurofibromatosis (NF1) Symptoms and Diagnosis: What to Look for and How to Get Tested

By Dr. Anaita Udwadia Hegde

Neurofibromatosis 1 (NF1) is a rare genetic disorder that affects the nervous system, causing tumours to form on nerves throughout the body. It is also known as Von Recklinghausen disease, named after the German physician who first described it in 1882. The condition is usually diagnosed in childhood, and symptoms can present in infancy or early childhood. In fact, it is estimated that a small percentage of cases of NF1 are diagnosed by the age of 1, and over 95% are diagnosed by the age of 8¹.

What is NF-1 and why does it happen? How does it present?

NF1 is caused by a mutation in the NF1 gene, which provides instructions for making a protein called neurofibromin. This protein helps regulate cell growth and division. When the NF1 gene is mutated, it can’t produce enough neurofibromin, which leads to the growth of tumours called neurofibromas.

These tumours can develop anywhere in the body, including on the skin, nerves, brain, spinal cord, and other organs. They are usually non-cancerous (benign), but in rare cases, they can become cancerous (malignant).

NF1 also affects other parts of the body, including the bones, eyes, and endocrine system. People with NF1 may have distinctive physical features, such as freckles in unusual places, brown skin patches, lumps under the skin, and skeletal abnormalities ^[1].

Who is at risk?

NF1 affects about 1 in 3,000 people worldwide². It can affect both males and females of all ethnicities. The condition is usually inherited from a parent, but in about half of all cases, it occurs spontaneously due to a new mutation in the NF1 gene.

What are the symptoms to look out for, and how is it diagnosed?

The average age of diagnosis for NF1 is 8 years old even though they may have symptoms since birth. ^[4] The symptoms of NF1 can vary widely from person to person. Some people may have only a few symptoms, while others may have many.

The most common symptoms of NF1 include:

• Multiple neurofibromas (lumps on or under the skin). In the case of Plexiform Neurofibroma, these symptoms may vary and could present differently. A plexiform neurofibroma may include a visible lump or bump under the skin that can grow rapidly, pain, and functional impairment if the tumour grows near a nerve or vital organ
• Cafe-au-lait spots (light brown spots on the skin)
• Freckles in unusual places (such as the groin or armpit)
• Skeletal abnormalities (such as scoliosis or bowed legs)
• Optic nerve glioma (a tumour on the nerve that connects the eye to the brain)
• Two or more Lisch nodules (tiny, harmless tumours on the iris of the eye).
• Bone abnormalities, such as abnormal curving or bowing of the long bones.
• Learning disabilities or attention deficit hyperactivity disorder (ADHD)

If a person meets two or more of these criteria, they can be diagnosed with NF1.

Diagnosing NF1 usually involves a physical exam, a medical history, and genetic testing. Genetic testing can also be done to confirm the diagnosis and to identify whether the NF1 gene mutation was inherited or occurred spontaneously. Further, a doctor may also order imaging tests, such as an MRI or CT scan, to look for tumours in the brain or spinal cord.

In the case of children, it is essential to note that not all children with NF1 will have all of these symptoms. Some may have only a few café-au-lait macules or mild bone abnormalities, while others may have multiple neurofibromas and significant learning disabilities.

What are the treatment options for this condition?

There is no cure for NF1, and treatment is focused on managing the symptoms and complications of the condition. Incidentally, people with NF1 have a 15-fold increased risk of developing optic nerve glioma compared to the general population³. Treatment options may include:

• Surgery to remove tumours or correct skeletal abnormalities
• Medications to manage pain or other symptoms
• Monitoring and treatment for complications such as high blood pressure or optic nerve glioma
• Education and support for learning disabilities or ADHD

Latest treatment options:

Since there is no cure for NF1, treatment aims to manage the symptoms and complications of the condition. Treatment options may include:

• Surgery to remove neurofibromas or plexiform neurofibromas that are causing disfigurement, functional impairment, or pain.
• Medications to control seizures or other neurological symptoms, such as headaches.
• Radiation therapy or chemotherapy for malignant peripheral nerve sheath tumours (MPNSTs) or optic pathway gliomas.
• Regular monitoring for complications, such as high blood pressure, scoliosis, or learning disabilities.

In recent years, there has been increasing interest in developing targeted therapies for NF1 that specifically address the underlying genetic defect.

Prognosis

The outlook for people with NF1 varies widely depending on the severity of their symptoms and the complications they experience. Some people with NF1 have mild symptoms and live normal, healthy lives. Others may experience significant complications that can affect their quality of life or even be life-threatening. Regular monitoring and treatment can help manage the symptoms and complications of NF1 and improve the prognosis for people with this condition.

Management of NF1 in children:

NF1 is a lifelong condition that requires ongoing management. Children with NF1 should have regular check-ups with a healthcare provider who is familiar with the condition. Regular monitoring can help identify and manage any complications of NF1, such as tumours, bone abnormalities, or learning disabilities.

(The author is Director of Neurosciences – SRCC Narayana Children’s Hospital, Hon. Consultant – Wadia Children’s Hospital- Jaslok Hospital & Research Center. Views expressed are personal and do not reflect the official position or policy of the FinancialExpress.com.)