Phakomatoses: Bullet Points

Phakomatoses, also known as neurocutaneous disorders, are a broad group of diseases that involve the central nervous system, skin, and retina.

• Neurofibromatosis type 1
  • Also known as peripheral neurofibromatosis or von Recklinghausen syndrome.
  • Most common of the phakomatoses.
  • Plexiform neurofibromas
  • CNS: Optic pathway gliomas (typically juvenile pilocytic astrocytoma) that can involve any part of the optic pathway: optic nerve, optic chiasm, optic tracts, lateral geniculate bodies, and optic radiations. Astrocytomas can also occur elsewhere in brain. Unidentified bright objects on T2-weighted images in dentate nuclei of cerebellum, brainstem, basal ganglia, and thalami, less commonly in cerebrum. These are not visible on T1-weighted images and don't enhance.
  • Chest: Focal thoracic scoliosis, posterior vertebral scalloping, dumbbell-shaped neurofibromas expanding the neural foramina. Weakness of meninges in the spine leads to arachnoid cysts or lateral meningoceles.
  • MSK: Anterolateral bowing of the tibia with or without a hypoplastic fibula, often with focal narrowing and intramedullary sclerosis or cystic change at the apex of the angulation. Characteristic rib abnormalities due to bone dysplasia or erosion from adjacent neurofibroma ("ribbon ribs"). Sphenoid wing dysplasia (can lead to pulsatile exophthalmos and herniation of the temporal lobe). Uncommon: Subperiosteal hemorrhage of the tibia.
  • Vascular: Intracranial aneurysms, stenosis, and moyamoya syndrome
  • 10% risk of development of malignant peripheral nerve sheath tumors
• Neurofibromatosis type 2
  • Also known as central neurofibromatosis, or MISME (Multiple Inherited Schwannomas, Meningiomas, and Ependymomas) syndrome. Radiologists like this because definitive diagnosis, unlike neurofibromatosis type 1, requires imaging.
  • CNS/PNS: Bilateral vestibular schwannomas, meningiomas, gliomas, ependymomas (intramedullary mass in spine), and congenital cataracts. Schwannomas can involve multiple cranial nerves, spinal nerve roots, peripheral nerve sheaths. Intraspinal schwannomas also dumbbell-shaped and expand neural foramina (most commonly intradural/extramedullary but may be extradural or both).
• Tuberous sclerosis:
  • Also known as Bourneville syndrome
  • Classic triad of epilepsy, mental retardation, and facial angiofibroma (adenoma sebaceum is misnomer) uncommonly seen
  • CNS: Hamartomas: Retinal hamartomas; Cortical or subependymal tubers (may calcify), subependymal nodules, and subependymal giant cell astrocytomas (SEGA, not generally seen >~20 years). White-matter abnormalities: "migration lines" seen as bands of myelination defect or gliosis.
  • Chest: Pulmonary lymphangioleiomyomatosis, multifocal micronodular pneumocyte hyperplasia, cardiac rhabdomyoma.
  • Abdomen: Multiple renal cysts, renal angiomyolipoma.
  • MSK: Periungal fibroma
• Sturge-Weber-Dimitri:
  • Also known as encephalo-trigeminal angiomatosis.
  • MSK: Cutaneous capillary angioma (port-wine stain) typically in V1 distribution.
  • CNS: Intracranial leptomeningeal angiomatosis ("tram-track" calcification of cortex), congenital glaucoma and choroidal angioma on same side as port wine stain. Imaging may show an enlarged globe from glaucoma (possibly related to the choroidal angioma).
• von Hippel-Lindau:
  • Also known as retino-cerebellar hemangioblastoma.
  • CNS: Retinal and central nervous system hemangioblastomas and endolymphatic sac tumors. Retinal hemangioblastomas (also known as retinal angiomas) may lead to retinal detachment.
  • Abdomen: renal cysts and tumors, pancreatic cysts and tumors (neuroendocrine tumors and serous cystadenoma), pheochromocytomas, and epididymal cystadenomas.

Practical points

• In NF1 all nerve sheath tumors are neurofibromas. In NF2, almost all are schwannomas or mixed tumors.
• Dumbbell-shaped lesions: If Solitary, think Schwannoma, which occurs more commonly in the Sensory root. If Multiple, think Neurofibroma.

References

• Akpinar E. The tram-track sign: cortical calcifications. Radiology. 2004 May;231(2):515-6.
• Cheema JI, Grissom LE, Harcke HT. Radiographic characteristics of lower-extremity bowing in children. Radiographics. 2003 Jul-Aug;23(4):871-80.
• Jones J, Brenner C, Chinn R, Bunker CB. Radiological associations with dermatological disease. Br J Radiol. 2005 Jul;78(931):662-71.
• Leung RS, Biswas SV, Duncan M, Rankin S. Imaging features of von Hippel-Lindau disease. Radiographics. 2008 Jan-Feb;28(1):65-79;
• Lin DD, Barker PB. Neuroimaging of phakomatoses.Semin Pediatr Neurol. 2006 Mar;13(1):48-62.
• Umeoka S, Koyama T, Miki Y, Akai M, Tsutsui K, Togashi K. Pictorial review of tuberous sclerosis in various organs. Radiographics. 2008 Nov-Dec;28(7):e32.