Early onset or syndromic epilepsy

Gene: SEC31A

I don't know

PMID: 39725565 Almontashiri et al., 2025
Female proband; parents are first cousins. IUGR and multiple congenital anomalies were seen on the antenatal scan. She was born very small, with dysmorphic facial features. She had hypotonia with hyperreflexia, but no seizures. Head ultrasound revealed absent CC and an interhemispheric cyst. She had short bowed limbs, contractures, Wormian skull bones, shortening of the long bones, and microcephaly. She died at 15 days old due to bradycardia. Solo WES revealed a homozygous SEC31A splice variant c.1435-1G>A. Splice AI score is
Splice-Altering / strong (1) for this variant. RT-PCR showed exon skipping and overall reduction in SEC31A expression.

PMID: 40508110 AlTassan et al., 2025
Report of a 5yo male proband with global developmental delay, seizure disorder, hypotonia, spasticity, dysphagia, dysmorphic features, and bilateral hearing loss. Growth parameters indicated microcephaly, failure to thrive, and short stature. He was born to consanguineous parents. WES and WGS showed a homozygous SEC31A variant (c.1359C>G, p.Cys453Trp). Unaffected parents confirmed het.

Created: 13 Aug 2026, 4:54 p.m. | Last Modified: 13 Aug 2026, 4:54 p.m.

Panel Version: 9.65

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Halperin-Birk syndrome, OMIM:618651; neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies, MONDO:0032849

Publications

• 39725565
• 40508110

I don't know

Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. One homozygous terminating variant reported in sibs of consanguineous Bedouin parents, together with a Drosophila model in which loss of sec31a was embryonically lethal and associated with defects in eye and brain development, consistent with abnormal neurodevelopment.
Sources: Literature

Created: 13 Jul 2020, 5:59 p.m. | Last Modified: 27 Jul 2020, 10:07 a.m.

Panel Version: 2.128

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies 618651

Publications

• 30464055