Phakomatosis are diagnosed based on clinical signs and imaging findings that help not only to accurate the diagnose but also to guide the treatment and the follow-up.

Neurofibromatosis type one (NF-I): 

NF-I, also named von Recklinghausen's disease, is the most common hereditary neurocutaneous and tumoral syndrome inherited by a mutation in the gene that encodes the protein neurofibromin, a negative regulator of the proto-oncogene RAS ₁. 

In neuroradiology, the characteristic features of NF-I include:

• Optic nerve gliomas: Gliomas can affect anywhere of the optic pathway, more commonly the nerve. They are slow-growing tumor found as an enlargement of the nerve that enhance after contrast administration. Bilateral involvement of both optic nerves is a pathognomonic finding. They cause progressive loss of vision [figure 1] _{1, 2, 3}.

• Plexiform neurofibromas: They are the hallmark of the disease appearing as tumors arising from the sheath of the nerve with a diffuse or nodular shape. They may be multiple along the spine with an hourglass appearance expanding the foramina. They can malignize [figure 2] _1,2,3.

• Focal areas of signal intensity: They affect the white matter of the brainstem, basal ganglia, cerebellum, and thalamus. They are seen as hyperintense foci with no mass effect in T2 sequences and no enhancement after contrast administration. They decrease over the years and are uncommon in adults [figure 3] _1,2.

• Other less common findings include dural ectasia (scalloping of the posterior aspect of the vertebra that causes an increased dural cavity) or vascular abnormalities (arterial occlusion, stenosis or moyamoya disease) [figure 3] _1,2.

Cutaneous signs of patients with NF-I include freckles on the skinfolds, café ou lait spots (the earliest sign) or lisch nodules in the iris ₂. 

Tuberous sclerosis complex (TS):

TS, also known as Bourneville disease, is the second most common phakomatosis characterized by the formation of multiple hamartomas. 

It affects the genes TSC1 and TSC2 that encode the proteins hamartin and tuberin, tumor suppressor proteins of the mTOR cascade.

TS usually affects young adults with a triad of seizures, mental retardation and facial angiofibromas _{1, 2, 4}.

Radiologically, TS has specific features:

• Subependymal nodules: They are the best diagnostic clue, found lining the ependymal surface of the lateral ventricles as small hypointense nodules in T2 sequences that enhance after contrast. They calcify with time, so CT is useful to detect them [figure 4] _{2, 4}.

• Subependymal giant cell astrocytoma (SGCA): they grow from subependymal nodules usually located near the foramen of Monro. They appear iso-hypointense in T1 and iso-hyperintense in T2 sequences with strong enhancement after contrast administration. They also calcified [figure 4]_{2, 4}.

• Cortical tubers: Focal areas of cortical hyperintensity are best seen in the T2 or FLAIR sequences as tumefactive cortex and enlarged gyres, mostly in the frontal and parietal lobes. The more in number, the more the epileptic activity [figure 4] _{2, 4}.

• Radial migration lines of the white matter: they represent the heterotopic glia and abnormal neuronal migration that extent from the ventricles to the cortex, usually associated with cortical tubers ₄.

Other non-neurological anomalies include renal angiomyolipomas, cardiac rhabdomyoma, subungual fibromas or leiomyomas, among others ₂.

Neurofibromatosis type two (NF-II): 

Third in frequency, NF-II is an inherited disorder with a mutation in the gen NF2 encoding the protein Merlin _{2, 5}. 

Even though its name, NF-II does not usually present with neurofibromas or skin manifestations, but it is identified by multiple schwannomas, meningiomas and, ependymomas ₅.

• The distinctive lesions of the NF-II are the presence of bilateral vestibular schwannomas, masses located in the pontocerebellar angle that enter into the internal auditory canal [figure 5]. They might be asynchronous, making it difficult to differentiate from sporadic schwannomas ₂. 

• Countless schwannomas in other locations such as head, neck or spine might be found affecting spinal nerve roots or peripheral nerves. They appear as dumbbell-shaped enhancing masses that expand the neural foramina. They do not have a malignant or infiltration potential, which facilitates its total resection [figura 6]₂. 

• Moreover, meningiomas are found mostly in the extra-axial supratentorial compartment. In MRI they appear isointense to the parenchyma in T1 and T2 sequences with a dural base and homogeneous enhancement [figure 5]₅.

• Finally, multiple ependymomas are observed as intramedullary enhancing masses centrally located in the cord, isointense in T1 and hyperintense in T2 sequences [figure 7] ₂.

Von-Hippel Lindau syndrome (VHL):

VHL is a hereditary syndrome that follows a mutation in the VHL tumor suppressor gene that leads to uncontrolled angiogenesis and tumor formation ₆.

It is identified by the development of multiple tumors in different systems, with the hemangioblastoma (HB) being the prototype tumor ₆.

HB can be found in the retina where the role of MRI is limited, occasionally found as a tiny enhancing nodule. In the CNS, HB occurs most frequently in the cerebellum, spinal cord and brainstem as a cyst with a mural nodule hypointense in T1 and hyperintense in T2 sequences with strong enhancement. Because of the rapid growth of the cystic component, it causes mass effect leading to gait ataxia, dysmetria or diplopia [figure 8] ₆.

VHL presents tumors outside the SNC ( pancreatic and renal cysts, neuroendocrine tumors, clear-cell renal carcinoma, pheochromocytoma or papillary cystadenomas ) that help distinguish them from entities such as pilocytic astrocytoma, medulloblastoma or metastases ₆. 

Sturge-Weber syndrome (SW):

SW is a sporadic neurocutaneous disease caused by a mutation in the GNAC gene that causes dysregulation of the vascular system. It is characterized by facial port-wine stains, ocular hemangiomas and leptomeningeal angiomatosis ₇.

The angiomatosis is seen on MRI images as a typical pial enhancement after gadolinium administration. Other brain abnormalities include cerebral atrophy with calvarial thickening, subcortical calcifications with a tram-track appearance and enlarged choroid plexus [figure 9] _{2, 7}.

Lhermitte-Duclos syndrome (LDS):

LDS is a rare hamartomatous disorder associated with the Cowden syndrome, an autosomal dominant disorder with a mutation in the PTEN gene ₈.

LDS or dysplastic gangliocytoma presents with a slow-growing cerebellar tumor with a characteristic tigroid appearance on MRI, presenting with striations hypointense in T1 and hyperintense in T2 sequences [figure 10] _2,8. 

Due to its growing nature, the lesion causes a progressively mass effect, compressing the fourth ventricle and leading to hydrocephalus.  As a result, patients present with long term symptoms such as headache, ataxia or blurred vision that help differentiate it from acute entities (infarcts or cerebellar encephalitis) _2,8.