Neurofibromatosis (NF) is a genetic disorder that impacts the nervous system, leading to tumor growth on nerves and skin. The term “NF skin” refers to the characteristic skin changes that are frequently the first noticeable indicators of this condition. Recognizing these skin manifestations is important as they often serve as early clues, prompting further medical investigation.
Primary Skin Manifestations
Neurofibromatosis type 1 (NF1), the most common form of the disorder, presents with several distinct skin manifestations. These signs are often present from birth or appear during early childhood and are a significant factor in diagnosis.
Café-au-lait spots are flat, light brown patches resembling coffee with milk. While one or two are common, six or more spots larger than 5 millimeters in children or 15 millimeters in adults strongly indicate NF1. These spots can appear anywhere on the body and are often present before five years of age.
Neurofibromas are benign tumors arising from nerve tissue. They appear as soft, flesh-colored bumps varying in size from small pea-sized lumps to larger growths. Neurofibromas become more numerous and increase in size during teenage years and early adulthood, developing on or just under the skin.
Axillary and inguinal freckling, also known as Crowe’s sign, are small, dark freckles found in the armpits and groin folds. These freckles are smaller than café-au-lait spots and often appear by ages three to five years. Less common are plexiform neurofibromas, which are larger, often deeper, benign tumors that can involve multiple nerves and cause disfigurement, especially if located on the face.
Beyond the Skin: Other Signs of Neurofibromatosis
While skin manifestations are frequently the first and most apparent signs of NF1, the condition is systemic and affects various other parts of the body. Recognizing these skin changes is important, as they often lead to further medical evaluation for internal manifestations.
One common ocular finding is Lisch nodules, which are benign, yellow-brown raised dots on the iris. These small freckles do not typically affect vision and are often identified during an eye examination, usually appearing by puberty. Bone abnormalities are also associated with NF1, including scoliosis or bowing of the long bones in the legs. Changes in bone development and lower bone mineral density can contribute to these irregular bone formations.
Optic pathway gliomas are tumors that can affect the nerve connecting the eye to the brain, potentially leading to reduced vision or total vision loss. These tumors usually appear by age three. Beyond physical symptoms, NF1 can also have cognitive impacts; learning disabilities are common in children with NF1, as are attention-deficit/hyperactivity disorder (ADHD) and speech delays. Other potential signs include an unusually large head size (macrocephaly) and shorter than average height.
Diagnosis and Management
The diagnosis of Neurofibromatosis type 1 is primarily based on clinical criteria, with skin signs playing a significant role. The National Institutes of Health (NIH) established diagnostic criteria, and a diagnosis is often made if an individual meets two or more of these established criteria.
Genetic testing for the NF1 gene mutation on chromosome 17 can confirm the diagnosis but is not always necessary for routine clinical diagnosis. It is often reserved for atypical cases or for family planning, particularly when clinical signs are not fully developed in young children. Approximately half of NF1 cases arise from new genetic mutations, while the other half are inherited.
Management of NF1 is multidisciplinary, focusing on ongoing monitoring for potential complications and addressing symptoms as they arise. Regular check-ups, typically at least once a year, monitor symptom progression and detect changes early. This includes annual blood pressure measurements, visual acuity checks, and examinations of the skin for new or growing neurofibromas. Screenings for potential internal tumors or complications, such as annual eye exams to check for optic nerve lesions, are also part of routine care.
Symptomatic treatment for skin issues may involve surgical removal of bothersome neurofibromas, either for cosmetic reasons or to alleviate discomfort. In some cases, medication such as MEK inhibitors like selumetinib has been approved for treating symptomatic plexiform neurofibromas that are not suitable for complete surgical removal.