Neurofibromatosis Type 1 (NF1)
Description
● Introduction:
• The most prevalent autosomal dominant condition, with an incidence of 1:2000–1:3500.
• NF1 is a tumour suppressor gene found on 17q11.2.
50% of mutations are de novo, and 50% are familial.
• By age five, penetration is 100%, although expressiveness varies greatly.
• No racial or gender domination.
● Clinical characteristics:
➣ Cutaneous
• Café au lait spots (at least six macules, smooth edges, chocolate to yellow-brown).
• Crowe's sign, or intertriginous freckling.
• Localised plexiform cutaneous neurofibromas Ophthalmic
• Iris Lisch nodules.
➣ Gliomas of the optic pathway.
•Bone mineral density, scoliosis, pseudoarthrosis, and sphenoid wings are examples of skeletal osseous dysplasia. Neurological/CNS:
•Learning deficit, cognitive impairment.
• Headaches and epilepsy.
➣ Vascular:
• Cerebrovascular anomalies, renal artery stenosis Additional early cutaneous indicators in infancy and early childhood:
• Nevus anemicus and juvenile xanthogranulomas.
● Craniofacial and Oral Manifestations
➣ Soft tissue of the mouth
50% of the lingual papillae are prominent.
• Neurofibromas of the mucosa and gingiva (25%): tongue > buccal mucosa > lips/gingiva.
• Macroglossia, which is caused by plexiform neurofibroma.
• Neurofibroma-induced gingivitis and periodontitis.
Gingival melanin pigmentation is uncommon.
➣ Craniofacial
• Exophthalmia due to orbital/sphenoidal wing dysplasia.
• Enlarged foramina and mandibular canal widening.
• Retrognathia due to mandibular, condyle, and maxillary hyperplasia.
• Radiolucent jaw lesions, or intra-osseous neurofibromas.
• Rare involvement of TMJ.
➣ Dental issues include agenesis, hyperdontia, and retained or misplaced teeth.
• Defects in enamel (molar-incisor hypomineralization, opacities, and hypoplasia).
Caries risk: debatable.
● Histopathology:
• Schwann cells, perineurial cells, and fibroblasts are mixed together in neurofibroma.
• Schwann cells: 40–80%, sharp corners, wavy nuclei.
S100, type IV collagen, CD34, and neurofilament (TUBB3) are examples of IHC markers.
● The diagnosis:
➣ The 1988 NIH criteria: ≥2 characteristics
• ≥6 macules of café au lait (≥5 mm prepubescent, ≥15 mm postpubescent).
• One plexiform neurofibroma or at least two neurofibromas.
• Inguinal/axial freckling.
• Glioma optica.
• Two or more Lisch nodules.
• A distinctive osseous lesion (pseudoarthrosis or sphenoid dysplasia).
• An NF1 first-degree relative.
➣ For mosaic forms, distinction from Legius syndrome (SPRED1 mutation), and other rasopathies, molecular testing is crucial.
● Case Report Highlight:
➣ 51-year-old male with oral and cutaneous neurofibromas since puberty, cutaneous café au lait spots from infancy.
➣ Gingival nodules on the vestibular maxilla are intraoral lesions (biopsy → confirmed NF).
➣ History: many skin excisions, denosumab treatment for osteoporosis Infection of tooth 48 unrelated to NF1
➣ After 11 years, there has been no return of oral lesions.
Protocol
● Administration:
• Multidisciplinary, yearly surveillance (oncology, neurology, ophthalmology, dentistry, and dermatology).
• Surgery: for cancer, functional impairment, or deformity. There is a risk of bleeding.
➣ Drug treatment:
•Selumetinib (MEK inhibitor) is FDA-approved for treating children's symptomatic plexiform neurofibromas (68% shrinkage).
➣ Paediatric focus: severe deformity or organ impairment can be avoided with early management.
➣ Dental treatment includes rigorous recurrence monitoring and the removal of symptomatic oral neurofibromas to enable cleanliness.
● Particular Care:
➣ Neurofibromas of the skin
• Usually benign, treated for practical or aesthetic purposes.
• Radiofrequency ablation, CO2 laser, electrosurgery, or excision.
• Risk: scarring, bleeding, and recurrence.
➣ The Neurofibromas of Plexiform
• Surgery is frequently challenging because of vascularity and infiltration if there is disfigurement, compression of important tissues, or a suspected malignant alteration.
•Medical option: → FDA-approved selumetinib (MEK inhibitor) for children with plexiform NF that is symptomatic but incurable; response: ~68% shrinking in clinical studies.
➣ Oral Lesions
• Removal of intraoral neurofibromas that cause symptoms (gingival, tongue, buccal mucosa).
• Assists with dental health and function and lowers the chance of recurrence.
• Keep an eye out for malignant alterations, which are uncommon but possible in oral locations.
➣ Gliomas in the Optical Pathway
•Asymptomatic observation.
•If vision loss or progression occurs, intervention (chemotherapy, seldom radiation or surgery) may be necessary.
➣ Anomalies of the Skeletal System
• Bone dysplasia, pseudoarthrosis, and scoliosis can be treated orthopaedically with bracing, surgery, or physical therapy as necessary.
➣ Developmental and Cognitive Problems
• Early neuropsychological assessment.
Notes
For more information 10.3390/dermatopathology8010003
