Early onset or syndromic epilepsy

Gene: HEXB

Green List (high evidence)

HEXB appears to have a well-characterised association with Sandhoff disease where seizures can be a feature, e.g. PMID 22848519.

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
Sandhoff disease infantile juvenile and adult forms, 268800

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: Green.

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

Panel Version: 1.189

Comment on list classification: Updated rating from Amber to Green. Sufficient cases of Sandhoff disease with seizures (PMID:28553389, PMID:7626071, PMID: 30075786) for inclusion on panel.

Created: 1 Aug 2019, 12:25 p.m. | Last Modified: 1 Aug 2019, 12:25 p.m.

Panel Version: 1.185

PMID:28553389: Gowda et al., 2017 report a 1 year old boy with Sanhoff disease without hepatosplenomegaly, and a homozygous missense variant in HEXB (p.Cys534Tyr). The boy suffered from focal seizures from 11 months. A sibling died age 18 months with 'similar complaints'. Further controls or segregation analysis was not performed. The authors say the same variant was reported previously in a Japanese case which showed myoclonic epilepsy and hepatosplenomegaly (PMID:7626071).

Created: 4 Jul 2019, 2:12 p.m. | Last Modified: 4 Jul 2019, 2:12 p.m.

Panel Version: 1.125

PMID: 30075786: Tavasoli et al., 2018 studied 25 Iranian patients with Sandhoff disease. 8/25 patients had seizures (Table 2) with a mean age at presentation 5.6 months. HEXB gene mutation studies were performed in 8 patients, including 2 patients with seizures (novel HEXB variants were identified in patients 4 and 13).

Created: 4 Jul 2019, 2:05 p.m. | Last Modified: 4 Jul 2019, 2:05 p.m.

Panel Version: 1.124

PMID: 22848519. Zampieri et al., 2012 characterized 14 unrelated Sandhoff disease (SD) patients and identified 16 alleles (9 novel). 9/14 patients (from Italy, Argentina, Brazil, Turkey and China) developed seizures, although no further information is given about the phenotype. However, the authors suggest caution in interpreting molecular analyses: A second mutation was not detected in Italian patient SD3 (a deletion is likely the second allele), a novel alternative spliced HEXB mRNA variant was also present in normal control cells, and the high activity retained by the H212N change didn't correlate with the severe phenotype exhibited by patient SD11.

Created: 4 Jul 2019, 1:45 p.m. | Last Modified: 4 Jul 2019, 1:45 p.m.

Panel Version: 1.124

Comment when marking as ready: Based on reviewers' comments.

Created: 11 Dec 2018, 1:21 p.m.

I don't know

Seizures are a reported feature, although I am having trouble ascertaining how common these are.

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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Sandhoff disease, infantile, juvenile, and adult forms, MIM#268800

Publications

• 2967418, 21153386

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