Multiplicity as a Factor in Understanding NF1
The NF1 locus on the long arm of chromosome 17 is a very special gene in the human genome.
In terms of multiplicity, there are five pseudogenes on five other chromosomes;
it influences the formation and/or behavior of many tissues;
it is probably the locus with highest germinal mutation rate in humans
(1 in 10,000), with a disease frequency of 1/2,500-1/3,000.
There are several other multiplicities that persist in confounding our
understanding of this very common autosomal dominant disorder.
This editorial focuses on three considerations: 1) How many types of Neurofibromatosis are there?
2) How many types of NF1 neurofibromas are there? 3) What are the logical/causative
relationships of the numerous pathogenetic and clinical elements of the full-blown syndrome
or portions of it In 19821 and for the first two editions of my NF book.
I identified seven to eight relatively distinctive types of NF. Based on careful
literature reviews, the most common and most consistent phenotype was labeled as NF1.
The next most consistent and somewhat common phenotype, with bilateral
vestibular schwannomas as the hallmark, was labeled NF2.
In 1987, an NIH Consensus Conference adopted the NF1 and NF2 terminology as
alternatives to “Von Recklinghausen disease” and “Bilateral
Vestibular Schwannomas,” respectively.
The only exceptions were the two non-neurofibroma disorders: NF2 is a totally distinct
schwannoma-generating disorder, as is Schwannomatosis; and NF5 identified
what we now know as the Legius syndrome.
An important general point here is that a body-wide distribution of multiple neurofibromas
is virtually always a type of VRD or NF1. In addition, an intragenic mutation or a whole gene deletion
involving the NF1 locus consistently manifests as some iteration of the VRD phenotype.
Neuro Open J. 2018; 5(1): e3-e4. doi: 10.17140/NOJ-5-e009
