Skeletal dysplasia

Gene: DDR2

Green List (high evidence)

spondylo-epi-(meta)-physeal dysplasias gp of SD. At least 3 cases reported.; Review on behalf of Tracy Lester

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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spondylometaepiphyseal dysplasia, short limb-hand type 271665, at least 3 cases reported

I don't know

After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed and remains BIALLELIC, autosomal or pseudoautosomal. Unlikely that patients with WARBURG-CINOTTI SYNDROME woud be tested via a skeletal dysplasia test. Primary phenotype is not skeletal dysplasia but contractures.

Created: 11 Mar 2026, 11:31 p.m. | Last Modified: 11 Mar 2026, 11:31 p.m.

Panel Version: 8.37

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: DDR2; Initial rating suggestion: green

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

Comment on mode of pathogenicity: Monoallelic DDR2 variants associated with Warburg-Cinotti syndrome, (OMIM: 618175), appear to have a gain of function mode of pathogenicity.

Created: 17 Feb 2025, 12:39 p.m. | Last Modified: 17 Feb 2025, 12:39 p.m.

Panel Version: 7.21

A change of mode of inheritance from biallelic to BOTH monoallelic and biallelic is requested, so that monoallelic DDR2 variants causing Warburg-Cinotti syndrome (OMIM: 618175) may be detected. Warburg-Cinotti syndrome includes skeletal dysplasia features (PMID: 23637089; 30449416). Functional studies of the two variants so far associated with Warburg-Cinotti syndrome, appear to have a gain of function mechanism. Cultured fibroblasts from the patients resulted in increased phosphorylation of DDR2 in comparison to the control fibroblasts, thereby causing autophosphorylation of the receptor (PMID: 30449416).

Created: 17 Feb 2025, 12:14 p.m. | Last Modified: 17 Feb 2025, 12:14 p.m.

Panel Version: 7.17

Comment on list classification: Used diagnostically by Ana Beleza (Guy's and St Thomas' NHS Foundation Trust)

Created: 21 Jun 2016, 12:44 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Warburg-Cinotti syndrome, OMIM: 618175

Publications

• 23637089
• 30449416

Green List (high evidence)

Tier 1

Created: 17 Jun 2016, 8:03 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spondylometaepiphyseal dysplasia, short limb-hand type 271665

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