Early onset or syndromic epilepsy
Gene: SPR
Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
Some evidence, phenotype is generally associated with tetrahydrobiopterin deficiency or sepiapterin reductase deficiency, both of which can exhibit seizuresCreated: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, 612716
Publications
Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene, however, the associated seizures appear to have been misdiagnosed and are infact myoclonic movements (PMIDs 16650784;21431957;28189489).Created: 3 Dec 2018, 12:54 p.m.
According to the recommendations of Arianna Tucci (Genomics England Clinical Fellow), the phenotypes associated with variants in SPR are not associated with epileptic seizures, rather with myoclonic movements as reported in the following publications: PMID 16650784: myoclonic jerks sometimes observed; PMID 21431957: myoclonic movements of hands and face; PMID 28189489 sudden stiffening of the whole body, extension of all extremities, and upward gaze lasting for several minutes often after meals in a 3 month old boy (including during a hospital stay), initially, mistaken for seizures, however 24h video-EEG showed no epileptiform discharges or any EEG correlate.Created: 3 Dec 2018, 12:51 p.m.
Seizures are part of the phenotype of this complex neurological disorder.Created: 22 Aug 2018, 2:21 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, MIM#612716
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to SPR.
Source NHS GMS was added to SPR.
Zornitza Stark: Seizures are part of the pheno
Gene: spr has been classified as Amber List (Moderate Evidence).
Publications for gene: SPR were set to
Mode of inheritance for gene: SPR was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: SPR were changed from to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency 612716
Expert Review Amber was added to SPR. Panel: Genetic Epilepsy Syndromes
SPR was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
SPR was created by Sarah Leigh