Review hereditary sensory neuropathy and children

[sbello]

Several issues here

OMIM has obsoleted MIM:608088 (xref for DOID:0070148) and merged it into MIM:614575 "CEREBELLAR ATAXIA, NEUROPATHY, AND VESTIBULAR AREFLEXIA SYNDROME; CANVAS " (not in DO), need to review this and decide what to do

There are several terms that are named hereditary sensory neuropathy [number][letter] but these are scattered under different parents.

1B, 1E, 4 are directly under hereditary sensory neuropathy
1D and 1F are under hereditary sensory and autonomic neuropathy type 1 which is a child of hereditary sensory neuropathy
2C is under hereditary sensory and autonomic neuropathy type 2
please check to see if these are all correctly placed. The groupings may be correct but it does make if hard to see all the hereditary sensory neuropathy 1 types at once.

Typo in the definition for DOID:0070156 (1D) " A hereditary sensory and autonomic neuropathy type 1 characterized dult onset of a distal axonal sensory neuropathy..." missing the a in adult

[allenbaron]

Thanks for adding this here, so we can address the complexity. I'll look into it and, if possible, try to get this done before the holidays.

[sbello]

Not a high priority, this was caught by the usual QC, but it did look messy

[allenbaron]

In that case, I think I'll make it a goal to get this one done by the January release.

[allenbaron]

I think the obsoletion of 'hereditary sensory neuropathy type 1B' (DOID:0070148) is pretty straightforward at least. The disease is not caused by a variant in the original chromosome locatoin identified but instead by biallelic repeat expansions in the RFC1 gene on chromosome 4p14, which OMIM had assigned to 'cerebellar ataxia, neuropathy, and vestibular areflexia syndrome' (CANVAS; MIM:614575).

@sbello unless you object, I'm just going to rename this to CANVAS and update it accordingly. I consider it to represent the same entity.

It'll take a bit longer to explore the classification of the other HSN/HSAN disease subtypes.

[allenbaron]

Reviewing DOID:0050548 (hereditary sensory neuropathy → hereditary sensory and autonomic neuropathy; HSAN hereafter) and the classification of its descendants has been quite the chore. At this point, I've completed review of all the HSANs included by OMIM in its HSAN phenotypic series (15 diseases + 3 grouping terms). I decided to pause to capture this as a checkpoint. There are additional diseases that, I think, still need review.

Information regarding this revision can be found in Curate-HSAN-classification_notes (Google Doc) and in Curate-HSAN (Google Sheet).

Sections:

• Key Points
• Classification details
• Remaining work

Key Points

1. At this point, classification of a disease as an HSAN is somewhat arbitrary, but also surprisingly stable.
2. All OMIM's HSAN phenotypic series types should be classified as HSANs following the 1975/1993 groupings or OMIMs updates.
3. The classification could really use comprehensive review and revision.
4. The diseases that could be classified as HSANs could be expanded, but it's not yet clear if it should be.

Details regarding HSAN classification

The classification of HSANs still relies on a classification system devised in 1975 by Dyck and colleagues¹, that has really only been updated once in 1993²³. It was based on the intersection of inheritance pattern, phenotype similarities, and age of onset and consisted only of HSAN1-5 (... and I'll just say that the distinction between them is not super obvious). The only truly unifying characteristic among them is that they all primarily include sensory peripheral neuropathy as a main feature, and many also include a variety of autonomic dysfunction. The variability in phenotype and loose connection via sensory neuropathy means that a lot of diseases COULD be classified as HSANs, but the latest review I could find which focused on HSANs specifically (including HSAN1-8)⁴, and most subsequent clinical literature seems to heavily rely on Dyck's classification with all deviation and updates following OMIM's naming and classification scheme closely (essentially mirroring the HSAN phenotypic series (PS162400) ... in this case, OMIM is serving as the de fact classifier through it's naming scheme).

One take away from this is that there is no reason for HSAN1E to be outside the HSAN1 grouping. It exhibits autosomal dominant inheritance with onset mostly in the 2nd-4th decade of life, so it's an HSAN1.

DO currently has 3 descendants of HSAN that are not included in OMIM's phenotypic series. Orphanet has significantly expanded the diseases that it includes as HSANs. Orphanet has additionally dropped the classification of sub-subtypes with. no grouping term for HSAN1 and HSAN2. It seems Orphanet may be following the grouping of Finsterer, et al⁵. They subgrouped HSANs only by inheritance (no HSAN1 or HSAN2 grouping terms) and include the PRNP, CCT5, and RAB7 genes as causes of HSAN subtypes but excludes PRDM12 (cause of HSAN8).

The definition of HSANs as a group is pretty loose--basically any peripheral neuropathy that is primarily sensory and/or autonomic in nature but not excluding diseases with minor motor neuron degeneration, which is why CMT2 is sometimes included, could be considered an HSAN--and, therefore, it's easy to be inclusive. It's not yet clear to me if this inclusiveness is supported by the clinical literature. In other words, the term "HSAN" and other related terms don't appear to be used in the literature for diseases beyond those defined by OMIM as HSANs. and those are the ones almost exclusively referred to in the literature as HSANs.

Work remaining

Basically, what remains is to decide whether to classify diseases as HSANs strictly following OMIM's phenotypic series, or with a more expansive view based on the definition of HSAN. This could include:

1. Review of diseases that are current descendants of HSAN in DO, but not in OMIM PS (3 diseases)
2. Review of diseases that could be classified as HSANs but are not currently (e.g. Marsili syndrome)
3. Add missing diseases which are or might be considered HSANs (e.g. SCN9A-related diseases)

I think I need to do 1 to finalize this issue and at least part of 3 (add SCN9A-CIP and HSAN2D), but not sure I should try to address 2 or complete 3 as part of it.

Footnotes

1. DYCK P. J. Neuronal atrophy and degeneration predominantly affecting peripheral sensory neurons. Peripheral Neuropathy II. Published online 1975:791-812. ↩

2. DYCK PJ. Neuronal atrophy and degeneration predominantly affecting peripheral sensory and autonomic neurons. Peripheral Neuropathy. Published online 1993:1065-1093. ↩

3. https://en.wikipedia.org/wiki/Hereditary_sensory_and_autonomic_neuropathy_type_I#History ↩

4. Schwartzlow C, Kazamel M. Hereditary Sensory and Autonomic Neuropathies: Adding More to the Classification. Curr Neurol Neurosci Rep. 2019 Jun 20;19(8):52. doi: 10.1007/s11910-019-0974-3. PMID: 31222456. ↩

5. Finsterer J, Löscher WN, Wanschitz J, Iglseder S. Orphan Peripheral Neuropathies. Journal of Neuromuscular Diseases. 2021 ;8(1):1-23. DOI: 10.3233/jnd-200518. PMID: 32986679; PMCID: PMC7902989. ↩