Congenital myaesthenic syndrome

Gene: DOK7

Comment on phenotypes: Previous phenotypes:
Myasthenic syndrome, congenital, 10, 254300;Myasthenia, limb-girdle, familial;Limb girdle congenital myasthenic syndrome

Created: 22 Mar 2021, 1:44 p.m. | Last Modified: 22 Mar 2021, 1:44 p.m.

Panel Version: 2.22

I don't know

PMID: 16917026 (Beeson et al., 2006) identified a set of DOK7 mutations including a frameshift (rs606231128) in 16 of 21 patients with congenital myasthenic syndrome-10 (CMS10, OMIM:254300); PMID:17452375;22661499;18626973 Among 16 patients with CMS10, Selcen et al. (2008) identified 17 different mutations in the DOK7 gene.

Created: 10 May 2019, 11:07 a.m.

Review and rating from Michael Oldridge (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust), submitted by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group.

Created: 30 Apr 2019, 9:30 a.m.

Green List (high evidence)

see PanelApp

Created: 29 Apr 2019, 4:33 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Myasthenic syndrome, congenital, 10, 254300; Myasthenia, limb-girdle, familial; Limb girdle congenital myasthenic syndrome

Added 'treatable' tag based on information in PMID:26870666: pyridostigmine (the drug most frequently used for treatment of congential myaesthenia (CMS) is not effective or is even detrimental in DOK7- and COLQ-related CMS, while beta-adrenergic agonists (ephedrine, salbutamol) show some sustained benefit. Also in 'Actionable Gene Panel'.

Created: 9 Feb 2017, 9:11 a.m.

Comment when marking as ready: Green review plus >3 cases of DOK7 mutations causing Congenital Myasthenic Syndrome-10 (OMIM:254300).

Created: 26 Jan 2017, 4:29 p.m.

Comment on mode of inheritance: Mode of inheritance confirmed in OMIM.

Created: 26 Jan 2017, 4:22 p.m.

Green List (high evidence)

Causes a congenital myasthenic syndrome predominantly affecting proximal muscle groups. Variable age of onset.

Covered by the Oxford Congenital Myasthenia Service

Created: 24 Jan 2017, 5:20 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Limb girdle congenital myasthenic syndrome

Publications

• PMID: 16917026
• PMID: 17452375
• PMID: 22661499

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