Paroxysmal central nervous system disorders
Gene: RHOBTB2
RHOBTB2 variant have been associated with Developmental and epileptic encephalopathy 64 (OMIM:618004) and as strong Gen2Phen gene for the same condition. PMID: 29276004 reports five RHOBTB2 variants in unrelated cases of OMIM:618004. The authors also present supportive functional studies.Created: 15 Aug 2023, 3 p.m. | Last Modified: 15 Aug 2023, 3 p.m.
Panel Version: 3.8
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.Created: 15 Aug 2023, 2:46 p.m. | Last Modified: 15 Aug 2023, 2:46 p.m.
Panel Version: 3.7
Publications
should be green based on previous reviewCreated: 24 Jul 2023, 1:14 p.m. | Last Modified: 24 Jul 2023, 1:14 p.m.
Panel Version: 3.1
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Eleven affected patients were identified. All had heterozygous missense variants involving exon 9 of RHOBTB2, confirmed as de novo in 9 cases. All had a complex motor phenotype, including at least 2 different kinds of movement disorder, e.g., ataxia and dystonia. Many patients demonstrated several features fulfilling the criteria for AHC: 10 patients had a movement disorder including paroxysmal elements, and 8 experienced hemiplegic episodes. In contrast to classic AHC, commonly caused by mutations in ATP1A3, these events were reported later only in RHOBTB2 mutation-positive patients from 20 months of age. All had ID, and many had seizures, so this represents an expansion of the phenotype rather than a distinct disorder.
Sources: LiteratureCreated: 13 Sep 2021, 8:18 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Developmental and epileptic encephalopathy 64 618004; Alternating hemiplegia
Publications
Tag Q3_23_promote_green tag was added to gene: RHOBTB2. Tag Q3_23_MOI tag was added to gene: RHOBTB2.
Phenotypes for gene: RHOBTB2 were changed from Developmental and epileptic encephalopathy 64 618004; Alternating hemiplegia to Developmental and epileptic encephalopathy 64, OMIM:618004; developmental and epileptic encephalopathy, 64, MONDO:0033373
Gene: rhobtb2 has been classified as Amber List (Moderate Evidence).
gene: RHOBTB2 was added gene: RHOBTB2 was added to Paroxysmal central nervous system disorders. Sources: Literature Mode of inheritance for gene: RHOBTB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RHOBTB2 were set to 33504645 Phenotypes for gene: RHOBTB2 were set to Developmental and epileptic encephalopathy 64 618004; Alternating hemiplegia Review for gene: RHOBTB2 was set to GREEN