Von Recklinghausen disease is also called neurofibromatosis type 1 and is marked by:
Pathophysiology
syndrome secondary to genetic defect marked by benign neural tumors and characteristic skin changes
Signs and Symptoms of Von Recklinghausen disease
1) multiple neurofibromas 2) positive “button hole” sign (tumors invaginate into skin with pressure) 3) six or more cafe-au-lait spots greater than 1.5 cm 4) freckles in nonexposed skin areas, such as axillary and inguinal areas 5) scoliosis 6) pseudoarthrosis of tibia 7) peripheral nerve sheath tumors (Schwannomas) 8) CNS tumors (neurofibrosarcoma, glioma, malignant Schwannoma) 9) Lisch’s nodules (pigmented iris hamartomas) 10) infiltrative lung disease
Histology/Gross Pathology
1) cafe-au-lait spots in Von Recklinghausen disease are flat and uniformly light brown in color 2) benign neurofibroma may convert to malignant peripheral nerve sheath tumors
Associated Conditions
1) mental retardation 2) hydrocephalus 3) epilepsy 4) hypertension 5) short stature 6) increased tumor susceptibility 7) increased upper GI carcinoid tumors, especially in the ampulla of Vater
Biochemistry
1) gene defect that causes Von Recklinghausen disease is on chromosome 17 and causes lack of GTPase-activating protein 2) this causes overexpression of the ras oncogene (i.e., gene remains in “turned on” condition)
Inheritance and Epidemiology
1) autosomal dominant 2) defect is on chromosome 17q11.2 3) affects 1/4000
Treatment
1) daily alpha-interferon 2) some experts are trying antiangiogenic medications
Tips for USMLE
1) neurofibromatosis type 2 – marked by acoustic neuromas and meningiomas; caused by defect on 22q12 (missing merlin protein) 2) if patient has multiple large brown flat freckles, freckles in their axilla, and multiple rubbery soft tissue masses, think von Recklinghausen disease 3) if a patient has a carcinoid tumor in the ampulla of Vater, think von Recklinghausen’s 4) recurrent meningiomas 5) pigmented lesions in iris
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