SNP Shot: Genomic Insights

Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by changes in skin pigmentation and the development of tumors along nerves in various parts of the body, including the skin and brain. The symptoms and severity of NF1 can vary significantly from person to person.

A hallmark of NF1, appearing in nearly all affected children, is the presence of multiple café-au-lait spots. These are flat, hyperpigmented patches of skin that are darker than the surrounding area. These spots tend to increase in both size and number as the child grows. Additionally, freckling in the underarms and groin area commonly develops during childhood.

Most adults with NF1 will develop neurofibromas, which are benign (non-cancerous) tumors typically found on or just beneath the skin's surface. These tumors can also occur along nerves near the spinal cord or in other areas of the body. In some individuals with NF1, malignant peripheral nerve sheath tumors, which are cancerous tumors, may develop along nerves, often appearing during adolescence or adulthood. Furthermore, individuals with NF1 have a higher risk of developing other cancers, such as brain tumors and leukemia (cancer of the blood-forming tissue).

During childhood, benign growths called Lisch nodules frequently appear in the iris (the colored part of the eye). These nodules generally do not affect vision. Some individuals with NF1 may also develop optic gliomas, which are tumors that grow along the optic nerve (the nerve connecting the eye to the brain). Optic gliomas can potentially lead to reduced vision or complete vision loss, although in some instances, they may have no impact on vision.

Other signs and symptoms of NF1 can vary and may include high blood pressure (hypertension), short stature, an unusually large head (macrocephaly), and skeletal problems like scoliosis (an abnormal curvature of the spine). While most individuals with NF1 have normal intelligence, learning disabilities and attention-deficit/hyperactivity disorder (ADHD) are frequently observed.

Inheritance:

NF1 follows an autosomal dominant inheritance pattern. This means that individuals with NF1 are born with one mutated copy of the NF1 gene in each cell. In approximately half of the cases, this altered gene is inherited from a parent who also has NF1. The remaining cases arise from new mutations in the NF1 gene, occurring in individuals with no family history of the disorder. Unlike many other autosomal dominant conditions where a single altered gene copy is sufficient to cause the disorder, the development of tumors in NF1 requires mutations in both copies of the NF1 gene. The second NF1 gene mutation occurs during an individual's lifetime within specialized cells surrounding nerves. Consequently, nearly all individuals born with one NF1 mutation will eventually acquire a second mutation in many cells, leading to the development of the tumors characteristic of NF1.