What Is Neurofibromatosis Type 1

Introduction

Definition of neurofibromatosis type I (NF1)

Neurofibromatosis 1 (NF1) is a genetic condition that you are born with. It causes the growth of tumours along your nerves. Usually, these tumours are non-cancerous (benign) but they cause a wide range of symptoms.¹ 

Importance of understanding NF1 for individuals and families

For half of cases, NF1 can be passed from an affected parent to their child.¹ Therefore, it is important for individuals with the condition and for their families to understand NF1 well. 

This article will introduce the causes, symptoms, diagnosis, and the treatment and management of NF1. 

What causes NF1?

NF1 is a genetic condition that is passed through families.¹ This section will explain how NF1 is caused.

Genetic mutation explanation

Your DNA is a sequence of code that provides the building blocks for the structure and characteristics of your body. A gene is a short segment of DNA. 

Mutations occur when aspects of DNA are altered. This may result in changes in your genes and alterations in the characteristics of your body.²

The NF1 gene is highly complex and encodes a protein called neurofibromin. Neurofibromin is an important regulator of cell signalling pathways controlling various aspects of cellular processes.³ Therefore, changes, or mutations, in the NF1 gene result in wide and varied clinical symptoms.⁴

Inheritance patterns

Genes can be passed, or inherited, through families in different ways. These include autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, and mitochondrial inheritance.⁵ For the purpose of this article we will only cover autosomal dominant inheritance, however further information on the other inheritance patterns can be found on the NHS website. 

Autosomal dominant inheritance

NF1 is passed through families in an autosomal dominant manner.³ This means that it is passed through every generation of a family and every person who has the condition has an affected parent.⁵

Sporadic cases

Occasionally, NF1 may occur spontaneously, or sporadically, when the affected individual does not have a family history of the condition.⁶ 

Signs and symptoms of NF1

Due to the complexity of the NF1 gene, mutations cause wide and varied symptoms in affected individuals.⁴ In this section we will provide an overview of well-characterised signs and symptoms of NF1. 

Café-au-lait spots

Café-au-lait spots are birthmarks that can be found anywhere on the body. They look like light or dark brown patches that can vary in size. Whilst café-au-lait spots can be observed in anyone, NF1 is characterised by the presence of six or more café-au-lait spots.¹

Neurofibromas

Neurofibromas are soft, benign tumours that can be found under or on the skin, or along your nerves.¹ They can vary in size.¹ 

Lisch nodules

Lisch nodules are dome-shaped lesions found in the eye. They usually don’t cause any problems but are used to confirm the diagnosis of NF1.¹ 

Other symptoms

Learning disabilities

Many individuals with NF1 will have learning disabilities.¹ This may include:

• autism spectrum disorder 
• attention deficit hyperactivity disorder (ADHD) 
• developmental delay 

Bone deformities

Individuals with NF1 may also have bone deformities, for example scoliosis. 

Tumours along the optic nerve

Occasionally, individuals with NF1 may develop tumours along the optic nerve which may cause headaches or seizures. Other tumours may also be associated with NF1.¹ 

Freckling 

Individuals with NF1 may have clusters of freckles in unusual places. For example, under the breast, in the groin, or under the armpits.¹ 

Diagnosis of NF1

NF1 is diagnosed by a clinical examination and genetic testing. 

Clinical evaluation

Physical examination

In older children and adults, NF1 may be diagnosed by checking for the typical symptoms as listed above. Some babies will show symptoms from birth, however, some symptoms can take years to develop making it harder to form a firm diagnosis.⁷ 

Family history

Since NF1 is a genetic condition, in suspected cases a family history will be taken to determine any previous occurrences of the condition in the family.⁷ 

Genetic testing

If the diagnosis is not clear from physical examination and family history, individuals may be offered a blood test to determine the presence of the faulty NF1 gene. However, this test is not that reliable and some children who test negative for the faulty gene will still go on to develop the condition.⁷ 

Treatment and management of NF1

Treatment for NF1 is usually managed by a multidisciplinary team of healthcare professionals. Since there is no cure and individuals with NF1 will live with the condition their whole lives, treatment focuses mainly on symptomatic relief and monitoring.⁸ 

Multidisciplinary approach

A multidisciplinary approach to treatment means a team of different healthcare professionals work together to manage the symptoms of individuals living with NF1.^1,8 Professionals who may be part of your multidisciplinary team managing your NF1 include:

Neurologists

Neurologists are specialist doctors who treat conditions affecting the brain and spinal cord. 

Dermatologists

Dermatologists are specialist doctors who treat conditions affecting the skin. 

Ophthalmologists

Ophthalmologists are specialist doctors who treat conditions affecting the eyes. 

Other specialists

Other specialists involved with the management of your NF1 may include geneticists, paediatricians and nurses, among many others.^1,8 

Symptomatic treatment

Symptomatic treatment in NF1 means treating the symptoms associated with the condition. These may include pain management and surgical options.⁸ 

Medications for pain management

You may be prescribed medications to help control any pain associated with the symptoms of NF1.⁸ 

Surgical options

Surgery may be required in NF1 for bone problems and tumours. Further information on surgery for NF1 can be found on the NHS website. 

Regular monitoring and surveillance

Individuals living with NF1 require regular monitoring for progression of their condition and symptoms.⁸ 

For children with NF1, this will look like a comprehensive examination each year which consists of a skin examination, vision test, bone assessment, behavioural testing, measurement of physical development, blood pressure testing, and assessment of their progress at school.⁸ 

For adults with NF1, monitoring will still ideally take place each year. This will look like a skin examination, bone assessment, blood pressure testing, neurological assessment, and checking in with emotional well-being and learning difficulties.⁸

Further information on monitoring of NF1 can be found on the NHS website. 

Living with NF1

Since there is no cure for NF1, affected individuals will live with the condition their whole lives.

Educational resources

Educational resources can be found at:

• NHS website 
• Brain Charity website 
• Nerve Tumours UK website 

Support groups

Part of your multidisciplinary team for the management of your NF1 may include a social worker. This individual will be able to provide you with support for living with the condition. 

Various support groups can also be found for individuals living with NF1, for example on the NHS website, the Brain Charity website, and the Nerve Tumours UK website.

Lifestyle adjustments

Various lifestyle adjustments may be recommended for managing your NF1. These include, but are not limited to: 

Physical activity

Being physically active and participating in exercise. 

Sun protection

Using sun protection to protect from sun damage. 

Family planning considerations

Since NF1 is a genetic condition, when considering a family it is important to understand the genetic inheritance of NF1. If you, or your partner, have a family history of NF1 you may want to consider a genetic counsellor prior to having a baby. Options may include: 

• Using a donor egg or sperm to have a baby
• Considering adoption
• Testing during pregnancy to determine if your baby will have NF1, e.g., by amniocentesis or chorionic villus sampling 
• Genetic testing prior to implantation of the egg in a laboratory

The NHS provides further information on family planning in NF1. 

Summary

NF1 is a genetic condition that is passed through families in an autosomal dominant manner. It causes a wide variety of signs and symptoms in affected individuals, including café-au-lait spots, neurofibromas, Lisch nodules, and learning difficulties. NF1 is diagnosed through a physical examination, family history and genetic testing.

Since there is no cure for NF1, management is by a multidisciplinary team who will help support treatment of the symptoms of the condition. Regular monitoring is important for individuals with NF1. Support and education are available for individuals with NF1, however, if you are concerned, speak to your healthcare professional.