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Neurocutaneous syndromes

Last updated: July 20, 2021

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Neurocutaneous syndromes (phakomatoses) are a diverse class of congenital disorders that affect organs of ectodermal origin, especially the skin, the central nervous system, and the eyes. The disorders most typically included in this class are neurofibromatosis type 1 (NF type 1, von Recklinghausen syndrome), neurofibromatosis type 2 (NF type 2), tuberous sclerosis, von Hippel-Lindau syndrome, Sturge-Weber syndrome, and ataxia telangiectasia. With the exception of Sturge-Weber syndrome, which is caused by a noninherited developmental anomaly of neural crest derivatives, and ataxia telangiectasia, which follows an autosomal recessive inheritance pattern, neurocutaneous syndromes disorders follow an autosomal dominant inheritance pattern, although spontaneous mutations are also possible. Characteristic features include neurofibromas, café au lait spots, axillary freckling, pheochromocytoma, optic glioma, and Lisch nodules (NF 1); bilateral vestibular schwannomas, meningiomas, ependymomas, and bilateral cataracts (NF 2); adenoma sebaceum, ash-leaf spots, shagreen patch, giant cell astrocytoma, cardiac rhabdomyoma, and renal angiomyolipoma (tuberous sclerosis); hemangioblastoma, angiomatosis, bilateral renal cell carcinoma, pheochromocytoma (von Hippel-Lindau syndrome); Port-wine stain and leptomeningeal angioma (Sturge-Weber syndrome); spider angioma, lymphoma, leukemia, gastric carcinoma, and ocular telangiectasia (ataxia telangiectasia). Diagnosis is based on clinical findings and is confirmed by genetic testing. Since there is no curative treatment, the management of neurocutaneous syndromes is symptom-oriented.

Epidemiology

Etiology

Pathophysiology

Clinical features

Neurofibromatosis type 1 (von Recklinghausen syndrome) [3]

Think CAFE SPOTS to remember features of NF type 1: Café au lait spots, Axillary freckling, neuroFibromas, nodules in the Eye, Skeletal abnormalities (e.g., Scoliosis), high blood Pressure, Optic Tumor, Stature (usually Short).

Neurofibromatosis type 2 [6]

In NF Type 2, the mutation is in chromosome Twenty-2 and the clinical findings (schwannoma and cataracts) manifest on 2 sides.

Diagnostics

Differential diagnosis

Treatment

Prognosis

Epidemiology

Etiology

Pathophysiology

Clinical features [13][14]

Infantile spasms occur in children < 3 years of age. They can consist of head bobbing, flexor spasms, extensor spasms, or movements that mimic the startle response. They may be associated with psychomotor regression or behavioral changes.

HAMAARTOMASS: Hamartomas, Ash leaf spots, Mind (intellectual disability), Adenoma sebaceum, renal Angiomyolipoma, Rhabdomyoma, Tumor suppressor genes (TSC1 gene and TSC2 gene), autosomal dOminant, Mitral regurgitation, Astrocytomas, Seizures, and Shagreen patches.

Diagnostics [16]

Differential diagnosis

Treatment [16]

Prognosis [17]

  • Renal disease and epilepsy are the most common causes of death.
  • Life expectancy depends on severity of disease but can be normal if symptoms are mild and complications are treated accordingly.

Epidemiology

Etiology

Pathophysiology

Clinical features [19][20]

Characterized by the development of numerous benign and malignant tumors

Von HIPPEL-Lindau syndrome: Hemangioblastoma, Increased risk of renal cell carcinoma, Pheochromocytoma, Pancreatic lesions (cysts, cystadenomas, and neuroendocrine tumors), Eye Lesions (retinal angiomas or hemangioblastomas).

Diagnostics [20]

Differential diagnosis

Treatment [21]

Mainly consists of regular surveillance and, if necessary, surgical treatment of tumors

Prognosis [22]

Epidemiology

Etiology

Pathophysiology

Clinical features [24]

Vascular malformations involving the following:

SSTURGGE-Weber: Sporadic, port-wine Stain, Tram-Track calcifications, Unilateral, Recurrent strokes or seizures, Glaucoma, GNAQ gene, Epilepsy.

Diagnostics

Differential diagnosis

Treatment

Prognosis [27][28]

Epidemiology

Etiology

Pathophysiology

Clinical features [30]

The 4 A's of ataxia telangiectasia: ATM gene, Ataxia, spider Angiomas, and IgA deficiency.

Avoid x-ray exposure because of high sensitivity to radiation and increased risk of malignancy.

Diagnostics

Differential diagnosis [30]

Treatment

Prognosis

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