Early onset or syndromic epilepsy

Gene: CTSD

Green List (high evidence)

AR Neuronal ceroid lipofuscinosis 10. Only Sintola et al, 2006 of the patients listed in OMIM record appear to have epilepsy as part of phentype.

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
Ceroid lipofuscinosis, neuronal, 610127

Publications

• 16670177

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: John Taylor and Helen Lord. 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. Epileptic seizures are an accepted phenotype of CLN10 disease (MIM:610127). Epilepsy reported as part of the symptoms in at least 2 families in literature (PMID:16670177 and PMID:26059544) PLUS animal model of epilepsy (PMID:10995834). Therefore 2 cases + clear animal model is sufficient evidence for diagnostic rating.

Created: 20 Nov 2018, 12:16 p.m.

PMID:26059544 (Meyer et al 2015) report 2 siblings with CLN10 disease who showed intractable seizures and respiratory insufficiency immediately after birth. A homozygous insertion (c.268_269insC) in exon 3 of the cathepsin D gene was found in both infants.

Created: 20 Nov 2018, 12:13 p.m.

Animal mode: CatD-deficient mice develop seizures and progressive retinal atrophy, becoming blind (See PMIDs:10995834 and 16685649).

Created: 20 Nov 2018, 12:13 p.m.

Siintola et al. (2006, PMID:16670177) identified homozygosity for a 1-bp duplication (764dupA, Y255X) in exon 6 of the CTSD gene in a Pakistani infant with CLN10 disease (MIM:610127) from consanguineous parents. 2 other brothers were affected by no DNA was available. All 3 infants died within 10 days of birth, after demonstrating intractable seizures, spasticity, and apnea.

Created: 20 Nov 2018, 12:12 p.m.

Green List (high evidence)

Seizures are a common feature of this metabolic disorder.

Created: 12 Aug 2018, 6:02 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ceroid lipofuscinosis, neuronal 10, MIM#610127

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

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)