Revise neurofibromatosis

[sbello]

Working on split of neurofibromatosis (DOID:8712) and I have a couple of questions/issue:

1. https://www.ncbi.nlm.nih.gov/pubmed/28640700 refers to 3 types of NF; 1, 2, and schwannomatosis. Schwannomatosis is also a synonym for neurilemmomatosis (DOID:3204) but the OMIM IDs for this are not types of NF OMIM but in ORDO these are NF3, so should we consider making DOID:3204 a child of NF in DO then splitting out the 2 subtypes. In ORDO NF3 also includes 162260 which in OMIM is NF3A). Gard also has Schwannomatosis (https://rarediseases.info.nih.gov/diseases/4768/index) with the synonym of NF3 and calls this a rare form of NF. Additional references: https://www.ncbi.nlm.nih.gov/pubmed/27617150

2. neurofibromatosis is currently a child of autosomal dominant disease but 2 of the OMIM entries (162210, 162260) associated with this have no defined inheritance pattern. In addition neurofibromatosis currently lacks so consider making the parent of neurofibromatosis 'nervous system disease' The associate the known autosomal dominant forms with autosomal dominant disease.

3. The final OMIM ID 162270 has only 2 references, and only 3 citations of the only reference in pubmed with 2 of those being about NF1. This entry has no gene or loci associated and hasn't been touched since 2003. I suggest dropping this mapping from DO.

[lschriml]

Wow, this took some time to figure out. I've made notes in this google doc: https://docs.google.com/spreadsheets/d/1vbWgLyqXO1hUc8Sku7Sgb1uLr3F1jJNOZ1_FGoM9pWo/edit#gid=2028624884

The "curation note" has my conclusions and to do's.

I think we should make a parent term - neurofibromatosis, with 3 subtypes: neurofibromatosis type 1 neurofibromatosis type 2 neurofibromatosis type 3 (aka schwannomatosis)

Cheers, Lynn

[allenbaron]

@lschriml it looks like you completed this issue? Is there something more that needs to be done?

[lschriml]

Hello Allen, it looks like type 3 has yet to be resolved.

neurofibromatosis is_a 'syndrome'

the type 3, from the google docs review, linked above, is_a: neurilemmoma

Looking at DOID:3204, neurilemmomatosis, synonym: Schwannomatosis It has OMIM: 162091, SCHWANNOMATOSIS 1. -->

To close this ticket, I think we need to: (1) do a new review of neurofibromatosis -- what are the subtypes reported in literature, and what is represented in OMIM, and other authoritative resources.

(2) Schwannomatosis -- needs a new review: -- what is represented in the DO ? -- is neurilemmomatosis == to Schwannomatosis -- Classification of Schwannomatosis -- should it be classified as a neurilemmoma, which is a neuroma, should it be classified as a syndrome ? -- checking literature, omim, etc.

         -- this definition looks like it should be moved to 'syndrome' 
             --> Schwannomatosis (pronounced SHWA-NOMA-TOSIS) is a genetic disorder that causes the growth of benign tumors called schwannomas along the nerves of the body and in the skull. Schwannomatosis is difficult to diagnosis because the main symptom is pain, and the tumors can be small and difficult to detect.

https://www.mountsinai.org/care/neurology/services/neurofibromatosis/types/schwannomatosis#:~:text=Schwannomatosis%20(pronounced%20SHWA%2DNOMA%2D,small%20and%20difficult%20to%20detect.

See also: https://www.hopkinsmedicine.org/health/conditions-and-diseases/neurofibromatosis/schwannomatosis

PubMed search: https://pubmed.ncbi.nlm.nih.gov/?term=Schwannomatosis

    -- what subtypes of schwannomatosis, see OMIM's phenotypic series: 
          https://www.omim.org/phenotypicSeries/PS162091

Cheers, Lynn

[allenbaron]

Based on the latest medical consensus only neurofibromatosis 1 should be included as a neurofibromatosis while NF2 & NF3 should become subtypes of schwannomatosis. I'll update NF2 & NF3 in the newer ticket for schwannomatosis (#1218).

• https://pubmed.ncbi.nlm.nih.gov/34012067/
• https://pubmed.ncbi.nlm.nih.gov/35674741/

OMIM appears to have additional diseases that may be subtypes of NF1. I'll revise neurofibromatosis as part of this ticket.

[allenbaron]

I’m trying to decide the placement for a number of neurofibromatosis disease variants all caused by mutations in neurofibromin 1 (HGNC:7765). These are the diseases:

1. neurofibromatosis 1 (NF1)
   • this is the classical syndrome
   • the definition will be updated based on the recent international consensus to “characterized by multiple cafe-au-lait spots, skin fold freckling, neurofibromas, optic gliomas, Lisch nodules or choroidal abnormalities in the eye, or a specific bone abnormality that has_material_basis_in the NF1 gene on chromosome 17q11.2. Bone abnormalities include a distinctive osseous lesion such as sphenoid dysplasia, anterolateral bowing of the tibia, or pseudarthrosis of a long bone.”
2. neurofibromatosis-Noonan syndrome (NFNS)
   • characterized by phenotypes of both NF1 and Noonan syndrome
   • no Noonan syndrome subtypes defined by OMIM are caused by mutation in the neurofibromin 1 gene
3. spinal neurofibromatosis (SNF)
   • characterized by neurofibromas at every spinal root, may or may not have other phenotypes of NF1
4. Watson syndrome
   • characterized by short stature, pulmonary valve stenosis, multiple cafe‐au‐lait spots, and intellectual disability^[ref1]

My impression is that spinal neurofibromatosis is considered a subtype of NF1, while NFNS and Watson syndrome are not considered subtypes, especially given that they don't necessarily include the development of neurofibromatoses.

[ref1]: Witkowski L, Dillon MW, Murphy E, S Lebo M, Mason-Suares H. Expanding the Noonan spectrum/RASopathy NGS panel: Benefits of adding NF1 and SPRED1. Mol Genet Genomic Med. 2020;8(4):e1180. doi:10.1002/mgg3.1180 PMID:32107864

[allenbaron]

'chromosome 17q11.2 deletion syndrome' (DOID:0060403) might also be an appropriate descendant of RASopathy (possibly as a child of neurofibromatosis or 'neurofibromatosis 1'). It is currently a child of 'chromosomal deletion syndrome' (DOID:0060388). If changes are made it should remain a child of 'chromosomal deletion syndrome', whether asserted or inferred.

A more specific review of that disease may be needed. Since it has an appropriate place currently, I'm going to go ahead and close this issue.