• It is a multisystemic disease characterized by skin lesions, bone lesions and specific tumors. NF-1 is more common.
Etiology
• NF-1 is inherited in an autosomal dominant manner and its gene is on chromosome 17. It is a protein-neurofibroma. Neurofibromatosis Type 2 (NF-2) also shows an autosomal dominant inheritance. Its gene is on chromosome 22. The protein is merlin/schwhannomin.
Pathophysiology
• Neural crest cells have a migration disorder during embryonic development.
• It causes abnormal growth in Schwann cells or peripheral nerves, cranial nerves and nerve roots and the formation of tumors including the peripheral and autonomic nervous system. Tumors in the nerve roots cause spinal cord compression. Plexiform neurofibromas are typically localized in the orbit or temporal region of the face.
• In addition to central nervous system tumors, Wilms tumor, hematological malignancy (leukemia), rhabdomyosarcoma, pheochromocytoma increase.
NF-1 Diagnostic Criteria
1) Six or more cafe-au-lait spots larger than 5 mm in prepubertal individuals and greater than 15 mm in postpubertal individuals (this finding is present in all patients)
2) Freckling in the axillary and inguinal region
3) Presence of two or more Lisch nodules (iris hamartoma)
4) Two or more neurofibromas or 1 plexiform neurofibroma
5) Bone lesions {sphenoidal dysplasia, cortical examinations in long bones such as tibia)
6) Optic gliomas
7) Positive NF-1 history in first-degree relatives Two of these findings are required to be positive for diagnosis.
NF-2 Diagnostic Criteria
Diagnosis is made with 1 of the following 4 criteria.
1) Bilateral 8th nerve tumor {acoustic neuroma) (schwannoma) (has 90-9% of patients)
2) Positive NF-2 history in first-degree relatives + at least 2 of unilateral acoustic neuroma or meningioma, schwannoma, glioma, neurofibroma, posterior subcapsular lens opacities
3) At least 2 of unilateral acoustic neuroma + meningioma, schwannoma, glioma, neurofibroma, posterior subcapsular lens opacities
4) Multiple meningiomas (2 or more) + unilateral vestibular schwannoma or schwannoma, glioma, neurofibroma, at least 2 of them cataracts, cafe-au-lait spots and skin neurofibromas are more rare in NF-2.
Hypertension is common in patients with neurofibromatosis because of the frequent incidence of mental retardation and renal artery stenosis.
Lab
• There is no specific laboratory finding.
• On radiological radiographs: Developmental disorder of sphenoid wings, enlargement of cranial nerve foramina, J-sella. Enlargement of intervertebral foramina on spinal radiographs, anterior meningocele. Scoliosis on vertebral radiography, decreased density in long bones.
• MRI: It is the most sensitive method for demonstrating spinal cord, brain tumors, optic glioma and acoustic nerve schwannoma. It should be repeated every 1-3 years.
• Renal artery stenosis can be demonstrated with renal vascular imaging methods. (The cause of hypertension in NF-1 is renal artery stenosis or pheochromocytoma). Renal imaging methods should be repeated every 1-3 years.
Neurofibromatous complications
1. Learning difficulties (most common)
2. Seizures
3. Moya moya
4. Transient ischemic attack (TIA) + hemiparesis
5. Cognitive defect
6. Malignant neoplasms
7. Scoliosis
Treatment
• Removal of acoustic neuromas and tumors originating from the spinal cord is the basis of treatment.
• If there is renal artery stenosis, it should be corrected.