Neurofibromatosis type 1

Overview

Board takeaway: Refer changing oral or facial masses promptly and check blood pressure; unexplained hypertension changes epinephrine and anesthesia planning.

Café-au-lait macules and neurofibromas are recognition clues.

How does Neurofibromatosis type 1 affect dental management?

• Changing lesions: Biopsy or refer for a growing, painful or changing lesion (malignant transformation)
• Blood pressure: check before care; unexplained hypertension needs medical workup. Renal artery stenosis and pheochromocytoma are possible causes; ask about pheochromocytoma before epinephrine or GA.
• Oral lesions: remove neurofibromas that interfere with function or hygiene; recurrence is common.
• Communication: adapt teaching to learning difficulties.

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New pain, rapid growth, or neurologic change raises concern for malignant transformation and needs imaging and biopsy through specialist care. Stable lesions are managed from their functional and hygiene effects.

Exam pearl

What is Neurofibromatosis type 1?

An autosomal dominant NF1-related condition with pigmentary changes and tumors along nerves, with variable skeletal, neurologic, and learning manifestations.

What are the main systemic features of Neurofibromatosis type 1?

• Genetics: NF1 (neurofibromin, a RAS regulator) mutation; autosomal dominant, ~50% de novo; ~1 in 3,000
• Pigmentary criteria: 6 or more café-au-lait macules over 5 mm before puberty or over 15 mm after puberty, and axillary/inguinal freckling
• Other criteria: 2 or more neurofibromas or 1 plexiform neurofibroma; optic pathway glioma; 2 or more iris Lisch nodules on slit-lamp examination or 2 or more choroidal abnormalities on OCT/near-infrared imaging; a characteristic osseous lesion; or a heterozygous pathogenic NF1 variant at 50% variant allele fraction in apparently normal tissue. Molecular findings with a lower allele fraction need assessment for mosaic NF1.
• Diagnostic threshold: at least 2 criteria without an affected parent; at least 1 for a child of a parent meeting NF1 criteria.
• Pigmentary-only findings: also consider Legius syndrome; at least one of the two pigmentary findings should be bilateral. Sphenoid wing dysplasia does not count separately when an ipsilateral orbital plexiform neurofibroma is present. These are the 2021 consensus criteria.
• Development and skeleton: Learning disability and ADHD common; scoliosis, short stature
• Blood pressure: hypertension from renal artery stenosis or pheochromocytoma
• Tumor risk: malignant peripheral nerve sheath tumor in plexiform lesions

What oral findings occur in Neurofibromatosis type 1?

• Oral involvement in many patients; the tongue is the most common site of oral neurofibroma
• Enlarged fungiform papillae; gingival or palatal neurofibromas
• Radiograph: enlarged mandibular foramen and canal, widened inferior alveolar canal, coronoid notch deformity
• Plexiform neurofibroma causing facial and jaw asymmetry, displaced or impacted teeth

For Neurofibromatosis type 1, what do rapid growth and pain in an oral neurofibroma require?

• Malignant peripheral nerve sheath tumor suspected
• Urgent referral for imaging and biopsy

A child has six café-au-lait macules and axillary freckling. What is the likely diagnosis and inheritance?

• Leading diagnosis: NF1; autosomal dominant, with about half of cases arising de novo.
• Confirm macule size: over 5 mm before puberty or over 15 mm after puberty. At least one of the two pigmentary findings should be bilateral.
• Interpret cautiously: these are two NF1 diagnostic criteria, but pigmentary-only disease can also be Legius syndrome.
• Refer: genetics/pediatric assessment; do not treat the skin pattern alone as proof of NF1. Current criteria also include molecular and ophthalmologic findings beyond the classic clinical signs.

Sources

• Supplemental diagnostic criteria: International consensus (2021): Revised diagnostic criteria for NF1 and Legius syndrome
• Supplemental systemic features: MedlinePlus Genetics: neurofibromatosis type 1
• Supplemental study guide: Pediatric Dental Study Guide: Neurofibromatosis
• Management of Dental Patients with Special Health Care Needs
• Management Considerations for Pediatric Oral Pathology