Fetal anomalies
Gene: USP18The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 3 Mar 2022, 11:19 a.m. | Last Modified: 3 Mar 2022, 11:19 a.m.
Panel Version: 1.836
Comment on list classification: With addition of the recently reported case (PMID:31940699) there is now a total of three families with pseudo-TORCH syndrome due to biallelic variants in USP18 (two carrying the same founder variant).
A rating upgrade from Amber to Green should be considered and therefore this gene will be flagged for review at the date of next GMS panel update (added 'for-review' tag).Created: 9 Oct 2020, 10:24 a.m. | Last Modified: 9 Oct 2020, 10:24 a.m.
Panel Version: 1.104
Added 'treatable' tag as clinical remission was achieved in a patient following rapid genetic diagnosis and subsequent treatment with the JAK inhibitor ruxolitinibCreated: 9 Oct 2020, 10:20 a.m. | Last Modified: 9 Oct 2020, 10:20 a.m.
Panel Version: 1.103
- PMID: 31940699 (2020) - One additional unrelated case - Saudi Arabian boy with a homozygous splice-site variant (c.1073+1G>A) in USP18, presented pseudo-TORCH syndrome characterised by hydrocephalus with seizures, intraventricular haemorrhage, brain calcifications, necrotizing cellulitis, systemic inflammation, multiple organ failure, and respiratory failure. This was the only patient to survive beyond the perinatal period owing to supportive care and prompt treatment with ruxolitinib. At the time of publication, the child was 3-years-old and was in full remission of clinical manifestations while continuing to receive oral ruxolitinib. He continues to grow normally, however authors note delay in developmental milestones.Created: 9 Oct 2020, 10:19 a.m. | Last Modified: 9 Oct 2020, 10:19 a.m.
Panel Version: 1.103
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Pseudo-TORCH syndrome 2, 617397
Publications
Kept rating as Amber on advice from Anna de Burca (Genomics England Clinical Team): fetally releavant phenotype but insufficient evidence for Green rating.Created: 25 Jul 2019, 8:04 a.m. | Last Modified: 25 Jul 2019, 8:04 a.m.
Panel Version: 0.311
Rated as 'Probable' in original PAGE list. Rated green on 'Intracerebral calcification disorders' panel and phenotype (pseudo-TORCH syndrome) is appropriate for Fetal panel, as noted by Helen Brittain and Anna de Burca (Genomics England Clinical team). However, kept rating as Amber for now based on insufficient evidence to support causation: One publication (Meuwissen et al. 2016, PMID:27325888) with two families (Turkish and German) with pseudo-TORCH syndrome-2 and homozygous or compound het variants in USP18. Segregation shown in 5 affected individuals plus an unaffected sibling. Cells from patients in both families showed complete absence of the USP18 protein.Created: 22 Jan 2019, 9:07 a.m.
DDG2P rating in original PAGE list: Probable for Severe pseudo-TORCH syndromeCreated: 11 Dec 2018, 9:05 a.m.
Phenotypes
Pseudo-TORCH syndrome 2, 617397
Publications
Tag for-review was removed from gene: USP18.
Source Expert Review Green was added to USP18. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: usp18 has been classified as Amber List (Moderate Evidence).
Publications for gene: USP18 were set to
Phenotypes for gene: USP18 were changed from Severe pseudo-TORCH syndrome to Pseudo-TORCH syndrome 2, 617397
Tag treatable tag was added to gene: USP18. Tag for-review tag was added to gene: USP18.
gene: USP18 was added gene: USP18 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: USP18 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: USP18 were set to Severe pseudo-TORCH syndrome