Trait Document

Neurofibromatosis type 1 (NF1) is a genetic condition characterized by multiple café-au-lait (i.e., coffee-colored) spots, freckling typically found in the armpit and/or the groin areas, Lisch nodules (i.e., dark pigmentation found within the iris of the eye that does not affect vision, and can only be detected by a special eye exam), and cutaneous neurofibromas (i.e., noncancerous growths or tumors that appear on the skin, usually first appearing on the chest, stomach, and back).

Many of the features observed in individuals with NF1 occur later in life; approximately 50% of children with NF1 who have no family history of the condition, meet the clinical criteria for a diagnosis of NF1 by age 1, but by age 8, almost all do. Multiple café-au-lait spots are often the first clinical feature of NF1 with approximately 80% of individuals having more than 5 café-au-lait spots by age 1. Optic pathway gliomas (i.e., a type of brain tumor that arises around the optic nerve – the nerve that connects the eye to brain) can be seen in a minority of children with NF1. Cutaneous neurofibromas typically begin appearing in adolescence and continue to develop throughout adulthood. They tend to increase in size during puberty and pregnancy. Scoliosis and high blood pressure are also often seen in individuals with NF1. Varying degrees of learning disabilities are often seen in individuals with NF1.

NF1 can be diagnosed either by meeting certain clinical criteria or by genetic testing for a change or mutation in a gene called NF1. This gene makes the neurofibromin protein. It is not entirely clear how mutations in the NF1 gene cause the features (e.g., café-au-lait spots and freckling) seen in NF1. However, it is know that the neurofibromin protein keeps cells from growing in an uncontrolled way. Mutations in the NF1 gene are thought to interfere with this process.

Management and surveillance of NF1 often includes regular physical exams, eye exams, and blood pressure monitoring. While optic pathway gliomas do not usually cause any symptoms, in some children, they can result in vision loss, growth problems or early puberty.

NF1 is inherited in an autosomal dominant pattern. This means inheriting one NF1 mutation is enough for an individual to be affected and show signs of NF1. The mutation can be inherited from an affected parent or it can occur brand new (de novo) in an affected child.

The risk to family members depends on whether or not the individual with NF1 has a parent affected with NF1. If a parent also has NF1, the risk of having a child with NF1 is 50% with each pregnancy. If a parent does not have NF1, the risk of future pregnancies being affected is very low.

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