Neurofibromatosis type 1 historical perspective

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Moises Romo M.D.

Neurofibromatosis type 1 was fully described in1882 by German pathologyst Friedrich von Recklinghausen, for which the disorder was eponymously named after him (von Recklinghausen disease), although the recognition of individuals with this phenotype probably dates back from the Hellenistic era.

• The first description of inviduals with Neurofibromatosis type 1 phenotype dates back from the XIV century, and probably even the Hellenistic era, made by Madigan, Schaw, and Masello, described as a “monstruous disease“.^[1][2]
• In 1785, English physician Mark Akensidi presents major reports about a patient, café au lait spots, rubbery lesions, cognitive imapirment, and a big head, which he named “wart man”.^[3]
• In 1830, Prusian anatomist and physician, Theodor Schwann described the nerve sheath cover that later was appreciated as the predominant cell type in neurofibromatosis.^[4]
• In 1847, Prusian pathologist, Rudolf Virchow stated that connective tissue tumors that contained nerves, should be classified apart from those that do not contain nerves, naming them “fibroma molluscum” or “elephantiasis molluscum”.^[5]
• In 1873, German ophtalmologist, Julius von Michel first reported the case of a patient with optic glioma.^[3][6]
• In 1882, German pathologist, Friedrich von Recklinghause systemically described neurofibromatosis type 1 with the presentation of two of his patients, recognizing it as a nosologic entity in his treatise “Über die multiplen Fibrome der Haut und ihre Beziehung zu den multiplen Neuromen“.^[1][4]
• In 1900, English physician A. Thomson describes Neurofibromatosis as an hereditary entity.^[4][3]
• In 1909, Suzuki was the first to describe an association between pheochromocytoma and neurofibromatosis type 1.^[4][3]
• In 1987, gene linkage studies localised the NF1 gene in chromosome 17.^[7]
• In 1987 this condition was uniformly recognized and clasified thanks to the National Institutes of Health (NIH) Consensus Development Conference.^[1]
• NF1 was cloned in 1990,^[8] and its gene product neurofibromin was identified in 1992.^[9]
• In 1999, Nielsen et al. discovered that loss of expression of p16 protein was the cause of malignant transformation in neurofibromatosis type 1.^[3][10]

• Probably the most famous case of neurofibromatosis type 1 was described in 1888, in England, with Joseph Merrick, the “elephant man“. This man had a difficult life, and was cruelly exhibited in circuses as a phenomenon. Joseph was born as a healthy child in 1862, but started to develop typical characteristics of the disease at age 2.^[11] By age 22, Merrick presented dysmorphic facies, macrocephaly, skin and bone deformities, but surprisingly, no cognitive impairment. He quoted:

“The deformity I am exhibiting now is because an elephant scared my mother; she walked down the street as a procession of animals paraded. A huge crowd gathered to watch them, and unfortunately, they pushed my mother under the feet of an elephant. She was very scared. She was pregnant with me, and this misfortune was the cause of my deformity“.

“Is true that my form is something odd, but blaming me is blaming God; Could I create myself anew would not fail pleasing you.If I could reach from pole to pole or grasp the ocean with a span, I would be measured by the soul. The mind´s the standard of the man.^[12]

• This patient was the inspiration for the 1980 movie “The Elephant Man“, by David Lynch.

• Society’s acceptance and understanding for neurofibromatosis type 1 has changed drastically over the time; from being a so-called a “monstrous disease”, to a well-known entity now in the day, compassion has grown for those individuals suffering from this condition thanks to the many research behind its behavior and characteristics. Advances in its treatment have made a great impact in the natural history of this disease, decreasing mortality and now focusing on a more multidysciplinary management.^[5]

• Joseph Merrick (the elephant man)^[13][12][11]
• Munya Yassir (actress)^[14]
  

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