Introduction

-Neurofibromatosis (NF) is a multisystem, autosomal dominant disorder 

-The most common forms are NF1 and NF2.

-NF-1 is associated with gene mutations on chromosome 17 and NF-2 on chromosome 22.

-These mutations result in loss of function of neurofibromin, which leads to increased protooncogene ras activity in neurocutaneous tissues, culminating in tumorigenesis. 

Symptoms & Signs 

Manifestations of NF Type 1 

Neurologic: peripheral and spinal neurofibromas 

Ophthalmologic: optic gliomas and iris hamartomas such as Lisch nodules

Dermatologic: Café au lait spots: well-circumscribed, light to dark brown macules with smooth borders); freckling in the axillary or inguinal regions; glomus tumors in the tips of the fingers and toes

Skeletal: Sphenoid wing dysplasia, scoliosis, macrocephaly, short stature, and pseudoarthrosis 

Vascular: Stenoses of renal and intracranial arteries

Endocrine: Pheochromocytoma, carcinoid tumors, and precocious puberty)

Manifestations of NF2 Type 2 

Otolaryngeal: Bilateral vestibular schwannomas (acoustic neuromas) leading to deafness, tinnitus, or vertigo

Neurologic: cranial meningiomas, spinal tumors, Distal, symmetric, sensorimotor neuropathy 

Dermatologic: Café-au-lait spots (less common than NF1)

Muscular: Muscular weakness or wasting

Diagnosis 

-Diagnosis is typically made during childhood based on the characteristic clinical features 

-Genetic testing for couples considering having children 

-CT or magnetic resonance imaging is useful for the diagnosis of optic glioma 

-Slit-lamp examination is useful for the diagnosis of Lisch nodules 

-Patients with NF2, as well as their family members, should undergo complete audiological testing to assess the level of hearing

Treatment 

-Café-au-lait spots and freckling: lasers, intense pulsed radiofrequency 

-Neurofibromas: Surgical excision, Carbon dioxide laser 

-Scoliosis, long bone dysplasia: Orthopedic interventions 

-Optic gliomas: chemotherapy with vincristine, cisplatin 

Prognosis 

NF1 patients have an increased risk of developing gastrointestinal stromal tumors.Plexiform neurofibromas can transform into malignant peripheral nerve sheath tumors; in contrast, malignant transformation of superficial neurofibromas is extremely rare