Skeletal dysplasia

Gene: HDAC4

I don't know

Brachydactylies (with extraskeletal manifestations) gp of SD. Brachydactyly MR syndrome is associated with a 2q37del. Only 2 cases with variants in the gene, but these have been reclassified as VUS on OMIM - haploinsufficiency associated with brachydactyly but not ID? amber/green? Note added by AW - HDAC4 yes. Listed in Bonafe (brachydactyly-MR). Seems good scientific basis to implicate HDAC4 in phenotype eg Jean-Marcais Am J Med Genet 14; Review on behalf of Tracy Lester/Andrew Wilkie

Created: 6 Mar 2019, 11:44 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Albright hereditary osteodystrophy type 3; Albright hereditary osteodystrophy-like syndrome; Brachydactyly-intellectual disability; Del(2)(q37) 600430

Publications

• 20691407
• 15521982
• 19365831
• 25402011

I don't know

Comment on list classification: After review with members of the GMS Musculoskeletal specialist test group and Genomics England Clinicians it was decided to rate the HDAC4 gene amber for SNVs, but to keep the region covering this gene green (ISCA-37394-Loss (2q37.3 terminal region (includes HDAC4) Loss))

Created: 3 Oct 2019, 9:38 a.m. | Last Modified: 3 Oct 2019, 9:40 a.m.

Panel Version: 1.203

Not associated with a phenotype in OMIM.
See review of this gene on Limb disorders panel - https://panelapp.genomicsengland.co.uk/panels/384/gene/HDAC4/
Conclusion was haploinsufficiency of HDAC4 appears to be associated with Brachydactyly type E but not always intellectual disability.

Created: 7 May 2019, 10:28 p.m.

This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: HDAC4 (2q37del); Initial rating suggestion: I don't know

Created: 6 Mar 2019, 11:36 a.m.

Comment when marking as ready: Associated with phenotype in G2P. Numerous reports of haploinsufficiency suggest involvement of HDAC4 in skeletal dysplasia..

Created: 12 Jul 2016, 8:23 a.m.

Green List (high evidence)

Tier 2

Created: 17 Jun 2016, 8:04 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Albright hereditary osteodystrophy type 3, Albright hereditary osteodystrophy-like syndrome, Brachydactyly-intellectual disability, Del(2)(q37) 600430

Variants in this GENE are reported as part of current diagnostic practice