Early onset or syndromic epilepsy

Gene: BTD

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

Green List (high evidence)

AR biotinidase deficiency also known as MCD - metabolic disorder characterised primarily by cutaneous and neurologic abnormalities due to inability to reutilise biotin - can treat with biotin. Wolf et al, 1985 - reviewed the clinical presentation of 31 children with late onset MCD due to biotin defic, symptoms usally appeared by 3 months with seizures as the most freq initial symptom. Other main features include hypotonia, hearing loss, optic atrophy, skin rash and alopecia. Pomponio et al,1995 - 10/25 patients with BTD - 7 bp del and 3 bp ins. In 1997 this group identified 21 mutations. The 2 most common were the del7/ins3 and R538C - 31/60 alleles. Remainmder were accounted for by 19 unique mutations. In 2000 this group identifed mutations in this gene in Turkish children diagnosed both clnically and by newborn screening. Is a biochemical test - not in the UK screening programme.

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
Biotinidase deficiency, 253260

Publications

• 24075304
• 25423671

Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 variants reported 18 cases of Biotinidase deficiency 253260 that include seizures as part of the phenotype.

Created: 12 Nov 2018, 5:14 p.m.

Comment on publications: PMID 24075304 mouse model, with seizures, PMIDs 4073853;3196050, seizures in patients

Created: 12 Nov 2018, 5 p.m.

Green List (high evidence)

Gene-disease association firmly established, and seizures are part of the phenotype.

Created: 8 Aug 2018, 1:38 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Biotinidase deficiency, MIM#253260

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)