Intellectual disability syndromic and non-syndromic
Gene: ROR2

ROR2 (receptor tyrosine kinase like orphan receptor 2)
EnsemblGeneIds (GRCh38): ENSG00000169071
EnsemblGeneIds (GRCh37): ENSG00000169071
OMIM: 602337, Gene2Phenotype
ROR2 is in 13 panels

2 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

DD/ID is not a key or consistent feature of Robinow syndrome, but has been reported in a proportion of affected individuals. Included here with Green rating for completeness.
Created: 27 May 2024, 3:16 a.m. | Last Modified: 27 May 2024, 3:16 a.m.

Panel Version: 0.5939

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Robinow syndrome, autosomal recessive, MIM#268310

Created: 27 May 2024, 3:16 a.m.
Last Modified: 27 May 2024, 3:16 a.m.
Panel version: 0.5939

Shani Stuart (Other)

Red List (low evidence)

PMID: 33937263 - Intellectual disability HP:0001249 in 3/21 individuals with ROR2 variants. Two individuals had a heterozygous missense variant c.1675G>A p.(Gly559Ser) and one individual had a heterozygous terminating variant c.613C>T p.(Arg205Ter). Note p.(Arg205Ter) is predicted to be NMD+ per Decipher.

PMID: 32954672 - 4/8 individuals with ADOM Robinow syndrome (RS) presented with some level of neurodevelopmental disability, however the authors note that altogether the cohort had an average level of neurocognitive function. Adaptive functioning was average in autosomal-recessive RS (RRS).

PMID: 32172608 - 2/3 children with AREC Robinow syndrome presented with intellectual disability. Described as 'homozygous mutations in the ROR2 gene on chromosome 9q22'. Actual variants not given.

Bacino CA. ROR2-Related Robinow Syndrome. 2005 Jul 28 [Updated 2019 Sep 12]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1240/ - Intellect is usually within the normal range, however, developmental delay has been reported.

Overall only one loss of function variant has been reported in relation to ID and there is conflicting information. Most sources suggest that intellect is usually within the normal range. Given that ID is broad and non-specific in the general population, some of the reported associations may have been by chance. Limited evidence for a relationship between ROR2 and ID.
Created: 21 May 2024, 10:01 a.m. | Last Modified: 21 May 2024, 10:01 a.m.

Panel Version: 0.5881

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Intellectual disability

Publications

PMID: 33937263, 32954672, 32172608

Created: 21 May 2024, 10:01 a.m.
Last Modified: 21 May 2024, 10:01 a.m.
Panel version: 0.5881

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
Genetic Health Queensland

Phenotypes

Robinow syndrome, autosomal recessive, MIM#268310

OMIM

602337

Clinvar variants

Variants in ROR2

Penetrance

None

Publications

Panels with this gene