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Neurofibromatosis Type 1

Summary

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  • Autosomal dominant genetic disorder characterised by café-au-lait spots, neurofibromas, and Lisch nodules
  • Caused by mutations in the NF1 gene, leading to uncontrolled cell growth and tumour formation
  • Imaging plays a crucial role in diagnosis, monitoring, and management of associated complications

Pathophysiology

  • Mutation in the NF1 gene on chromosome 17q11.2
  • NF1 gene encodes neurofibromin, a tumour suppressor protein
  • Loss of neurofibromin function leads to:
    • Increased Ras signalling
    • Uncontrolled cell proliferation
    • Formation of benign and malignant tumours

Demographics

  • Incidence: 1 in 2,500 to 3,000 live births
  • No ethnic or gender predilection
  • 50% of cases are familial, 50% are due to de novo mutations
  • Complete penetrance with variable expressivity

Diagnosis

  • Clinical diagnosis based on NIH diagnostic criteria :
    • Six or more café-au-lait macules (>5 mm in prepubertal individuals, >15 mm in postpubertal individuals)
    • Two or more neurofibromas or one plexiform neurofibroma
    • Axillary or inguinal freckling
    • Optic glioma
    • Two or more Lisch nodules
    • Distinctive osseous lesion (sphenoid dysplasia or tibial pseudarthrosis)
    • First-degree relative with NF1
  • Genetic testing for NF1 gene mutations

Imaging

  • MRI:
    • Brain:
    • Unidentified bright objects (UBOs) in basal ganglia, thalamus, and cerebellum
    • Optic pathway gliomas
    • Plexiform neurofibromas
    • Spine:
    • Dural ectasia
    • Spinal neurofibromas
  • CT:
    • Skeletal abnormalities:
    • Sphenoid wing dysplasia
    • Tibial pseudarthrosis
    • Scoliosis
  • Ultrasound:
    • Superficial plexiform neurofibromas
    • Screening for renal artery stenosis

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  • A 20-year-old patient presented after a seizure.
  • MRI showed bilateral vestibular schwannomas and many meningiomas (optic nerve sheath [red arrow], anterior falx and left parietal region).

Treatment

  • Multidisciplinary approach
  • Regular clinical and imaging follow-up
  • Surgical management:
    • Symptomatic or rapidly growing neurofibromas
    • Optic pathway gliomas causing visual impairment
  • Medical management:
    • Selumetinib for inoperable plexiform neurofibromas
    • Pain management
    • Treatment of associated conditions (e.g., hypertension, epilepsy)
  • Genetic counselling
  • Psychosocial support

Differential diagnosis

Differential Diagnosis Distinguishing Feature
Legius syndrome Absence of neurofibromas and optic gliomas
McCune-Albright syndrome Café-au-lait spots with irregular borders ("coast of Maine")
Multiple endocrine neoplasia type 2B Presence of medullary thyroid carcinoma and mucosal neuromas
Tuberous sclerosis Presence of ash-leaf spots and facial angiofibromas
Proteus syndrome Asymmetric overgrowth and vascular malformations
Klippel-Trenaunay syndrome Vascular malformations and limb hypertrophy
Bannayan-Riley-Ruvalcaba syndrome Macrocephaly and intestinal polyposis
LEOPARD syndrome Presence of lentigines and cardiac abnormalities
Noonan syndrome Distinctive facial features and congenital heart defects
Mosaic neurofibromatosis Localised or segmental distribution of neurofibromas