Early onset or syndromic epilepsy

Gene: SPR

Comment on mode of inheritance: Sepiapterin reductase deficiency typically follows an autosomal recessive pattern of inheritance. Two cases with different heterozygous variants have been reported (PMID: 29147684, 15241655) although with reduced penetrance in the familial cases and mild form of the disorder in the singleton.

Overall additional evidence is required to conclusively make an association with monoallelic variants and therefore updating the MOI from 'Both mono- and biallelic' to 'Biallelic'

Created: 13 Mar 2025, 5 p.m. | Last Modified: 13 Mar 2025, 5 p.m.

Panel Version: 7.58

I don't know

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

I don't know

Some evidence, phenotype is generally associated with tetrahydrobiopterin deficiency or sepiapterin reductase deficiency, both of which can exhibit seizures

Created: 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

• 11443547

I don't know

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.

Green List (high evidence)

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