Brain channelopathy

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, 4:58 p.m. | Last Modified: 13 Mar 2025, 4:58 p.m.

Panel Version: 1.82

Green List (high evidence)

Comment on list classification: Recommedation from Arianna Tucci to add SPR to this panel

Created: 3 Dec 2018, 1:05 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. Therefore this phenotype is relevant to the Brain channelopathy panel.
Sources: Literature

Created: 3 Dec 2018, 1:04 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Dystonia, dopa-responsive, due to sepiapterin reductase deficiency 612716