New Term Request: Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities --OR-- KDM6B-related neurodevelopmental disorder [name TBD]

[vjenkinsFB]

I'd like to request a term for neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities --OR-- KDM6B-related neurodevelopmental disorder [name TBD]. OMIM named this disorder based on the Stolerman 2019 paper (see citations below). In a newer paper, Rots 2023 suggests:

“However, after analyzing this large cohort of individuals with pathogenic KDM6B variants, we see that coarse facies, as well as mild distal skeletal abnormalities, are rare and not typical. As it currently stands, such designation could be misleading to professional and patient communities and therefore urgent redefinition is required. On the basis of the wide array of symptoms caused by pathogenic KDM6B variants in our cohort, we propose that the name “KDM6B-related NDD” would better describe this condition.”

Rots 2023 is what I need to curate for FB. I haven’t asked OMIM if they plan on changing this name. They haven’t curated Rots 2023 so clearly they didn’t look at it and decide not to change. No rush on making this decision, I don’t mind if you wait for OMIM before making it.

OMIM: https://omim.org/entry/618505

Potential definition: [name] has_material_basis_in heterozygous mutation in the KDM6B gene on chromosome 17p13. (Rots 2023 agrees that they found heterozygous variants.)

Potential parent term: autosomal dominant intellectual developmental disorder

Synonyms: [whichever name you don’t pick]; NEDCFSA

ClinVar search term: KDM6B[gene] AND ( ( ("clinsig has conflicts"[Properties]) OR ("clinsig pathogenic"[Properties] or "clinsig pathogenic low penetrance"[Properties] or "clinsig established risk allele"[Properties]) OR ("clinsig likely pathogenic"[Properties] or "clinsig likely pathogenic low penetrance"[Properties] or "clinsig likely risk allele"[Properties]) OR ("clinsig vus"[Properties] or "clinsig uncertain risk allele"[Properties]) ) AND (1[VARLEN]:1000[VARLEN] AND "single gene"[Properties]))

MedGen page(s) pointed to by the above: https://www.ncbi.nlm.nih.gov/medgen/C5193134/ Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities

MalaCards page: https://www.malacards.org/card/neurodevelopmental_disorder_with_coarse_facies_and_mild_distal_skeletal_abnormalities

HGNC entry for gene: https://www.genecards.org/cgi-bin/carddisp.pl?gene=KDM6B

Citations:

• https://pubmed.ncbi.nlm.nih.gov/31124279/ Stolerman ES, Francisco E, Stallworth JL, et al. Genetic variants in the KDM6B gene are associated with neurodevelopmental delays and dysmorphic features. Am J Med Genet A. 2019;179(7):1276-1286. doi:10.1002/ajmg.a.61173
• https://pubmed.ncbi.nlm.nih.gov/37196654/ Rots D, Jakub TE, Keung C, et al. The clinical and molecular spectrum of the KDM6B-related neurodevelopmental disorder. Am J Hum Genet. 2023;110(6):963-978. doi:10.1016/j.ajhg.2023.04.008

FlyBase paper(s) to curate with this term: FBrf0256700

My contact info: vjenkins@morgan.harvard.edu (FlyBase), 0000-0002-1567-7626. Thank you!

[allenbaron]

Thanks Victoria! I think it makes sense to wait for OMIM on this one to avoid the potential for competing names. Have you reached out to them about it yet? If not, I'm happy to.

[vjenkinsFB]

I haven't written OMIM about this yet, so if you don't mind asking whether they intend to change that it would be fantastic. Thank you!

[allenbaron]

OMIM has curated the publication by Rots and renamed their disease entry. I will review their changes and work to get it added in the next release.

[lschriml]

added name: Stolerman neurodevelopmental syndrome, DOID:0081443