The course of NF-1 varies considerably in various patients, but the majority have a benign course of the disease without developing major complications. In fact, diagnosis is usually made in middle-age or later in life. The variability in presentation appears to be at least partially genetically determined and is unrelated to the unaffected allele. Patients with NF-1 may present with the following[3][4]:

• Cafe-au-lait macules: Sharply defined light brown patches that vary in size from 0.5 cm to 50 cm, the majority are ten cm or less in size. They are the first feature of the disease and appear in all children affected by the disease. They increase in size and number during the first decade of life.
• Neurofibromas: These are soft iliac-pink tumors, mostly sessile and dome-shaped while some are pedunculated. Mostly found on trunk and limbs ranging from few millimeters to several centimeters in diameter. In females, they are prominent on the areola of the breast. The plexiform neuroma is a diffuse elongated neuroma along the course of the nerve, frequently trigeminal and cervical nerves are involved, and they usually present during the first two years of life. On palpation, they have a characteristic "bag of worms" sensation.
• Freckling: Axillary freckling in patients is usually pathognomonic for NF-1, and it is known as Crow's sign. It is present in around 70% of the individuals and appears later than cafe-au-lait spots. Freckling may also be present in other intertriginous areas like the groin.
• Lisch-nodules: They appear as dome-shaped lesions around the iris on slit-lamp-examination. They are present in over 90% of the affected individuals and are also known as pigmented iris hamartomas. They are usually asymptomatic but used as an aid to confirm the diagnosis.
• Oral lesions: Papillomatous neurofibromas of the hard palate, tongue, etc. are present in only 5% to 10% of cases.
• Skeletal abnormalities: Kyphoscoliosis occurs in 2% of the affected individuals, and high-level lesions may lead to respiratory difficulties. Pseudoarthrosis of tibia or radius occurs in about 1% of the cases. Sphenoid wing dysplasia is a characteristic abnormality in NF-1.
• Malignancies: Neurological tumors consist of optic nerve glioma, astrocytoma, and schwannomas. Intracranial tumors can cause seizures. Other malignancies reported to have associated with the disease are Wilms tumor, rhabdomyosarcoma, leukemia, retinoblastoma, and malignant melanoma.

The diagnosis of NF-1 is mainly clinical, based upon agreed clinical criteria which require two or more of the following conditions to be fulfilled[5]:

• Cafe-au-lait spots: six or more with the greatest dimension of 5-15mm.
• Neurofibromas: two or more of any type or one plexiform neurofibroma
• Freckling: axillary or inguinal
• Optic Gliomas
• Lisch nodules: two or more
• Bony lesions: sphenoid dysplasia and others
• Family history: a first-degree relative with the disease.

 There is no definitive treatment for NF-1 as being a genetic disorder and having multiple manifestations.[1][6][7][8] Treatment is mainly symptomatic for various NF-1 manifestations, for example:

• Carbon dioxide laser is used to excise most disfiguring neurofibromas, but hypertrophic or atrophic scars may result from the treatment.
• Surgery is indicated when patients present with pain and an increase in the size of a tumor.
• Seizures or epilepsy should thoroughly be investigated as a neurosurgical intervention is sometimes very beneficial for the patient.
• Follow-up every 12 months to assess different complications of the disease.
• All infants are screened with cranial MRI to look for neurological abnormalities.[9][10][11]
• Genetic counseling is very important in disease management. Informing the patients about the different complications of the disease is very important. And it should be made very clear to the patients regarding their children that 50% are likely to be affected, and the disease may be severe. First-degree relatives who have no disease manifestations are unlikely to carry the gene, and the risk for their offspring is small but not absent.

• Ataxia telangiectasia
• Klippel-Trenauney-Weber syndrome
• Legius syndrome
• Lipomatosis
• McCune-Albright syndrome
• Neurofibromatosis type 2
• Noonan syndrome
• Piebaldism
• Schwannomatosis
• Tuberous sclerosis

The outlook for patients with NF-1 is guarded and depends on the severity of the disease, presence of malignancy, and extent of the deformity. Those with mild disease can have a reasonable life expectancy, but those with moderate to severe disease have a poor quality of life.[12]

• Tibial and orbital dysplasia
• Plexiform neurofibromas
• Short stature and scoliosis
• Learning disabilities and attention deficit hyperactivity disorder
• Optic pathway glioma
• Systemic hypertension
• Moya Moya disease
• Malignant peripheral nerve sheath tumors
• Gastrointestinal stromal tumor
• Multiple endocrine neoplasia

The patient and parents should be aware of the prognosis and the possible complications that can develop. Genetic counseling should be offered prior to conception.

All genetic disorders are rare, and they are thought to be associated with extreme worrisome for the families. The main aim is to ensure proper diagnosis of the disease and genetic counseling of the affected families to prevent their children from the disease.

The presentation of patients with NF-1 is extremely variable and because the disorder affects many organs, it is best managed by an interprofessional team including nurse practitioners. While the disorder is benign, it is vital that healthcare workers closely monitor patients because many organ systems are involved. To improve patient outcomes, it is important to remember that a few patients may develop neurological tumors. Other malignancies reported to have associated with the disease are Wilms tumor, rhabdomyosarcoma, leukemia, retinoblastoma, and malignant melanoma. A thorough exam and serial imaging studies are the only way to identify the presence of these lesions.