Radial dysplasia

Gene: RAD21

Comment on list classification: Although limb abnormalities are a common feature of CdLS, only minor skeletal anomalies are associated with RAD21 variants. Other prominent features such as ID are more likely to prompt testing and therefore maintaining the Amber rating on skeletal panels for now.

Krab et al. 2020 (PMID: 32193685) collated details on 33 unrelated families (previously and newly published) with RAD21 alterations. In the 22 families with sufficient clinical data available, authors noted that major limb malformations are generally not present. However, minor skeletal anomalies such as clinodactyly of fifth finger (13), camptodactyly (3), scoliosis (2), hip dislocation/dysplasia (2) are reported.

Created: 15 Nov 2022, 12:08 p.m. | Last Modified: 15 Nov 2022, 12:08 p.m.

Panel Version: 1.22

Green List (high evidence)

Large series of over 40 individuals reported recently.

Created: 23 Jul 2020, 7:54 a.m. | Last Modified: 23 Jul 2020, 7:54 a.m.

Panel Version: 1.10

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cornelia de Lange syndrome 4, MIM# 614701

Publications

• 32193685

Comment when marking as ready: Only two cases to date. Watchlisted. In view of CdLS phenotype being associated with variable limb defects, it would be an appropriate phenotype for radial dysplasia but further evidence for causation needed.

Created: 11 May 2017, 12:44 p.m.

Comment on list classification: Two cases reported to date. Watchlist.

Created: 11 May 2017, 12:41 p.m.

Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for CRANIOECTODERMAL DYSPLASIA. At least 4 variants reported.

Created: 2 Jul 2020, 12:54 p.m. | Last Modified: 2 Jul 2020, 12:54 p.m.

Panel Version: 1.10

Comment when marking as ready: COSMIC census lists somatic RAD21 variants for AML, endometrium, colorectal and lung cancers. (Associated with phenotype Cornelia de Lange syndrome 4 614701 in OMIM and as a confirmed G2P. At least 2 variants reported in 2 cases. PHENOTYPE NOT RELEVANT TO THIS PANEL)

Created: 9 Mar 2017, 2:54 p.m.

Green List (high evidence)

Mode of inheritance
Unknown

Phenotypes
Acute myeloid leukaemia (AML); Especially in Down syndrome AML

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

Green List (high evidence)

Tier 3

Created: 17 Jun 2016, 8:07 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cornelia de Lange syndrome 4 614701

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