History of NF1 - Sydney Cognitive Development Centre

History of NF1
In 1882 Dr Frederick von Recklinghausen provided the first systematic
description of neurofibromatosis. He published two case reports in a
monograph entitled On Multiple Neurofibromas of the Skin and their
Relationship to Multiple Neuromas. Von Recklinghausen correctly
identified the pathology of the cutaneous and subcutaneous tumours
and coined the term “neurofibroma”. From this time the condition
became known as von Recklinghausen’s Disease.

It was not until the beginning of last century that Thomson (1900)
discovered the genetic nature of the disorder, demonstrating that the
disease was familial in 30/77 reported cases. In 1918 Preiser and
Davenport proposed autosomal dominant inheritance. From the end of
the nineteenth century, innumerable case reports of NF1 appeared in
the medical literature, often focusing on the more severe manifestations
and overestimating disease complications. The first large and
reasonably accurate surveys of the disease appeared in the 1950s
(Borberg, 1951; Crowe, Schull, & Neel, 1956). These early studies were
limited however as they failed to distinguish between different forms of
neurofibromatosis.

Interest in NF1 was sparked through John Hurt's portrayal of Joseph
Merrick in the film “The Elephant Man”. Joseph Merrick was a severely
disfigured man who lived in Great Britain during the late 1800's. He was
exhibited in "freak shows" and carnivals throughout the country. People
were morbidly fascinated by his grotesque appearance. In 1971, based
on the medical knowledge available to him at the time, Ashley Montagu,
suggested a connection with NF1 in his book, 'The Elephant Man'. The
psychological and emotional impact this erroneous connection had on
NF1 families at the time of a new diagnosis was immense. The image
of the physical deformities of Joseph Merrick was immediately brought
to mind. At the same time, significant research into NF began to be
conducted and support groups for affected individuals and their families
were established. In 1986, Tibbles and Cohen identified the medical
condition of Joseph Merrick as "Proteus Syndrome," a genetically
separate but similar condition to NF1. Unfortunately, the confusion of the
two conditions persists. The process of re-educating the medical
community, the media, and the general public continues.

Detailed research into the clinical manifestations and cognitive profile
has increased markedly over the past 15 years. In 1987, definitive
diagnostic criteria for NF1 and NF2 were proposed (National Institutes
of Health Consensus Development Conference, 1988), enabling
accurate and uniform clinical diagnoses of the two disorders. In 1990
the NF1 gene was cloned and its gene product, neurofibromin, was
identified (Wallace, Marchuk, Anderson, Letcher, Odeh, Saulino,
Fountain, Brereton, Nicholson, & Mitchell, 1990). A few years later the
NF2 gene was cloned and its gene product, merlin, was identified
(Rouleau, Merel, Lutchman, Sanson, Zucman, Marineau, Hoang-Xuan,
Demczuk, Desmaze & Plougastel, 1993). NF2 is also an autosomal
dominant disorder however it has been localized to chromosome 22, as
opposed to NF1, which has been localized to chromosome 17. The
genetic discrimination between these two disorders has further
alleviated diagnostic confusion.