Early onset or syndromic epilepsy

Gene: HOXA1

Red List (low evidence)

Limited number of variants reported in HOXA1, but of those reported are associated with Athabaskan brainstem dysgenesis syndrome which may include seizures (PMID 12833395).

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
Unknown

Phenotypes
Athabaskan brainstem dysgenesis syndrome, 601536 ; Bosley-Salih-Alorainy syndrome, 601536

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: Red.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

Added watchlist tag.

Created: 11 Dec 2018, 2:22 p.m.

Comment on list classification: Kept rating as Amber. HOXA1 is a Confirmed DD-G2P gene for Athabaskan brainstem dysgenesis syndrome and Bosley-Salih-Alorainy syndrome; seizures are a variable feature of these HOXA1 spectrum disorders but aren't present in all affected individuals. Reported individuals so far are all from Saudi families or the Athabascan Indian population. Of the 5 BSAS or ABDS individuals summarised with seizures in PMID:18412118, it's unclear how many are related and therefore how many individual cases there are. Therefore rated Amber awaiting further clear cases.

Created: 11 Dec 2018, 2:22 p.m.

PMID:18412118 (Bosley et al 2008) report 9 new individuals from 6 families (3 consanguineous Saudi families and 3 Native American families) who have homozygous variants of HOXA1 with either the Bosley-Salih-Alorainy Syndrome (BSAS) or the Athabascan Brainstem Dysgenesis Syndrome (ABDS). Seizures were seen in 2 patients (Saudi patients B1 and C1). Patient B1 had 2 unaffected siblings and six unaffected half siblings. Patients C1-C4 came from a consanguineous extended family, and seizures weren't noted in C2-C4. The Authors provide a summary, reporting seizures in 1/16 BSAS patients and 4/13 ABDS patients (it's unclear which of these patients are related).

Created: 11 Dec 2018, 2:19 p.m.

Holve et al., 2003 (PMID:12833395): Seizures reported in 4/10 ABDS patients, all of which are Athabascan Indian children. Genetic analysis was not performed.

Created: 11 Dec 2018, 2:18 p.m.

Comment on mode of inheritance: Biallelic MOI supported by the literature (e.g. PMID:18412118)

Created: 11 Dec 2018, 1:54 p.m.

I don't know

Biallelic variants in this gene cause a syndrome affecting hindbrain development, with BSAS and ABDS allelic disorders. Some patients with ABDS have been reported as having seizures; however, it is unclear whether this is a common part of the phenotype.

Created: 15 Aug 2018, 1:31 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Bosley-Salih-Alorainy syndrome, MIM#601536 and Athabaskan brainstem dysgenesis syndrome, MIM#601536

Variants in this GENE are reported as part of current diagnostic practice