When was neurofibromatosis discovered

Cushing later coined the term meningioma that remains widely accepted today [ 1 , 16 ]. Biggs in , Penfield in and Gardner and Turner in were among those to publish significant early reports on acoustic neuromas with meningiomas [ 1 , 5 , 30 , 42 , 83 ]. Cushing and Eisenhardt reviewed these cases, along with further reports that appeared early in the twentieth century, in their monograph on meningiomas [ 16 ]. In the following years, after several reports stating that NF2 presented a familial occurrence with autosomal dominant inheritance [ 1 , 22 , 28 , 29 ], acoustic neurinomas became accepted as a severe complication of the von Recklinghausen disease.

The family reported by Gardiner and Frazier [ 28 ], in particular, had 38 affected members over five generations: the affected members had early-onset deafness and balance problems and often died prematurely, and the authors also noted the particularity of the uniform expression of acoustic neuromas and the presence of limited signs of von Recklinghausen disease in these patients. Autopsy was performed on two affected members and revealed bilateral cerebellopontine angle tumours.

Reports of families with members affected by bilateral neuromas became more frequent in the second half of the last century, and the possible presence of a distinct mutation responsible for the disease was suspected [ 1 , 21 , 32 , 53 ].

In particular, the study by Moyes focused on four generations of an affected family, suggesting the presence of an entirely different autosomal dominant mutation, because many of the affected members presented a few signs of the classical von Recklinghausen disease but the distinctive bilateral acoustic neuromas [ 53 ].

When ultimately Young et al. This report and a subsequent study by the same group [ 43 ] covered nine generations of an American family, from the late s to the twentieth century.

Other NF1 complications were notably absent, and only 2 of 97 had more than one subcutaneous nodule. Genealogic tree of the family reported by Young et al. In the following years, different genetic origins of the two pathologies have been demonstrated, thus confirming the differentiation in two distinct pathologies [ 1 , 42 ].

Evolution of the concept of neurofibromatosis type 2. Arch Otolaryngol Head Neck — Ashrafian H Limb gigantism, neurofibromatosis and royal heredity in the Ancient World years ago: Achaemenids and Parthians.

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Adv Neurol — Cruveilhier J — Anatomie pathologique du corps humain, ou descriptions, avec figures lithographiees et coloriees, des diverses alterations morbides dont le corps humain est susceptible. Paris, France: Bailliere —8. Cushing H, Eisenhardt L Meningiomas. Their classification, regional behaviour, life history, and surgical end results. Springfield, IL, and Baltimore. Cushing H Tumors of the nervus acusticus and the syndrome of the cerebello-pontine angle.

Saunders, Philadelphia. Dandy WE An operation for the total removal of cerebellopontile acoustic tumors. Surg Gynecol Obstet — Emerson O Robert William Smith. Available at: www. Orphanet J Rare Dis Nord Med — Feeling A, Ward E A familial form of acoustic tumour.

BMJ — Foster WD A short history of clinical pathology. E Livingstone Ltd, Edinburgh, p. Med Rec — Kunstverlag, Passau. N Engl J Med — Mitt Grenzgeb Med Chir — Gardiner WT, Frazier CH Bilateral acoustic neurofibromas: a clinical study and field survey of a family of five generations with bilateral deafness in 38 members.

Arch Neurol Psych — Arch Neuropsych — J Hered —8. Edin Med J — Riv Pat Nerv Ment — Nature Happle R A rule concerning the segmental manifestation of autosomal dominant skin disorders.

Review of clinical examples providing evidence for dichotomous types of severity. Arch Dermatol — Happle R Mosaicism in human skin. Understanding nevi, nevoid skin disorders, and cutaneous neoplasia. Happle R Segmental forms of autosomal dominant skin disorders: different types of severity reflect different states of zygosity. Hecht F Recognition of neurofibromatosis before von Recklinghausen. Arch Psychiat — Henschen F Zur histologie und pathogenese der Kleinhirnbruckenwinkel tumoren.

Arch F Psychiatr House WF Acoustic tumor surgery: an historical perspective. Semin Hearing — Howell M, Ford P The true history of the elephant man. A new edition of the story of Joseph Carey Merrick whose tragic life and extraordinary fate are told in this book. London: penuin Books Ltd. Tumours of the nervous system. Knoblauch, J De neuromate et gangliis accessories. Frankfurt, Dissertation. Malkin HM Out of the mist: the foundation of modern pathology and medicine in the nineteenth century.

Science Jul 13 Science Jul 13 Von Recklinghausen neurofibromatosis type 1 NF1 is an autosomal dominant disorder found in about 1 in people. Citation s : Cawthon RM et al.

Cell 62 Wallace MR et al. October 18, Family Medicine. Wilmington, North Carolina. Medford, Massachusetts. Add or change institution. Save Preferences. Privacy Policy Terms of Use. Access your subscriptions. Free access to newly published articles. Purchase access.

Rent article Rent this article from DeepDyve. Access to free article PDF downloads. Spearheaded an international consortium analysis of children with NF1 and autism, which revealed new insights into the differences between autism in NF1 and that occurring in people without NF1 First demonstration that the specific germline NF1 gene mutation dramatically impacts optic glioma development and vision impairment Identification of a novel mechanistic target of rapamycin mTOR complex in the brain important for NF1 gene function Reported associations between allergic conditions and brain tumors in children with NF1 Generation of the first model of NF1 malignant peripheral nerve sheath tumor MPNST in which the timing and location of cancer development can be controlled.

Discovered genomic predictor of NF1-brain tumor development Launched a social skills program for teenagers with NF1 Teen NF Identified a new growth factor made by non-cancerous cells that control mouse optic glioma growth Discovered how RAS controls brain stem cell function Described the frequency of autism in children with NF1 Identified another treatment for NF1 optic glioma, now in clinical trial for children with NF1 brain tumors Used advanced sequencing methods to identify a new gene involved in NF1 malignant sarcoma malignant peripheral nerve sheath tumors Reported the first use of NF1 patient-derived stem cells to generate brain nerve cells Discovered why NF1 optic glioma stem cells are less sensitive to some brain tumor treatments.

Performed the first whole genome sequencing of NF1-associated low-grade glioma Demonstrated that non-cancerous cells in NF1-associated optic glioma are necessary for tumor formation Showed that reduced dopamine levels are also partly responsible for learning problems in NF1 genetically-engineered mice Characterized the spectrum of sleep problems in people affected with NF1 Collaborated with Jazz St.