Neurofibromatosis type 1 is a congenital condition caused by a mutation in the NF1 gene.

Genes function by providing genetic “blue-prints” that instruct the development, function, multiplication and eventually death of cells. When the genetic material contained in the nucleus is altered, the cell may fail to undergo programmed cell death (apoptosis) and instead survives when it would not normally do so. These abnormal cells then go on to multiply uncontrollably and give rise to lumps or tumors.

The NF1 gene, which is found on chromosome 17, normally produces a special protein that regulates and promotes the growth of nerve tissue. This protein can “switch off” growth once the tissue has developed to a certain degree. When the gene is mutated, however, this protein fails to exert this control over the growth, which continues to occur in an uncontrolled manner, giving rise to a tumor.

The condition is inherited in an autosomal dominant manner, meaning only one parent needs to possess the faulty gene for the child to be at risk of developing the condition. In around 50% of cases, the gene is inherited from one of the parents and the remaining cases are caused by sporadic development of the mutation in people with no family history of the condition.

The severity of the condition is not inherited and the child of a parent with a severe form of neurofibromatosis 1 may have only mild symptoms, for example. Patients who have no family history of the condition and develop the mutation sporadically are also capable of passing the illness on to their offspring.

Diagnosis

Neurofibromatosis type 1 is commonly diagnosed based on typical clinical features of the condition. A diagnosis can be confirmed when two or more of the following symptoms are present:

1. Six or more pale brown “café au lait” spots of more than 5 mm diameter in children or more than 15 mm in adults. Freckles in the armpits or groin.
2. The presence of two or more neurofibromas (lumps that form beneath or on the surface of the skin) or the presence of one plexiform neurofibroma – a growth that forms at a point where multiple nerve branches meet.
3. Tumors of the optic nerve. An optic glioma does not necessarily affect sight.
4. Two or more small brown spots in the iris called Lisch nodules.
5. Bone abnormalities such as bowing of the leg.
6. A family history of NF1.

Diagnosis

Imaging studies such as X-rays and MRI scans may be performed to check bone development and look for tumors. An electroencephalogram (EEG) of the brain may be recommended if the patient has experienced seizures. A skin biopsy may be carried out to check for cancerous cells. In unconfirmed cases, genetic testing may be performed to check whether the NF1 gene is mutated.