Congenital myaesthenic syndrome

Gene: CHRND

Comment on phenotypes: Previous phenotypes:
Congenital Myasthenic Syndrome, Dominant/Recessive;Myasthenic syndrome, slow-channel congenital, 601462;Slow channel myasthenic syndrome;fast channel myasthenic syndrome;Acetylcholine receptor deficiency syndrome;?Myasthenic syndrome, congenital, 3A, slow-channel, 616321;?Myasthenic syndrome, congenital, 3C, associated with acetylcholine receptor deficiency, 616323;Myasthenic syndrome, congenital, 3B, fast-channel, 616322

Created: 22 Mar 2021, 1:17 p.m. | Last Modified: 22 Mar 2021, 1:17 p.m.

Panel Version: 2.17

I don't know

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
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Congenital Myasthenic Syndrome, Dominant/Recessive; Myasthenic syndrome, slow-channel congenital, 601462; Slow channel myasthenic syndrome; fast channel myasthenic syndrome; Acetylcholine receptor deficiency syndrome; ?Myasthenic syndrome, congenital, 3A, slow-channel, 616321; ?Myasthenic syndrome, congenital, 3C, associated with acetylcholine receptor deficiency, 616323; Myasthenic syndrome, congenital, 3B, fast-channel, 616322

Comment when marking as ready: Green review plus >3 cases of CHRND mutations causing Congenital Myasthenic Syndromes (OMIM:616321, 616323 and 616322).

Created: 26 Jan 2017, 3:57 p.m.

Comment on mode of pathogenicity: The 'Slow-channel' form of myasthenic syndrome results from kinetic abnormalities of the AChR channel, specifically prolonged opening and activity of the channel (gain of function).

Created: 26 Jan 2017, 3:52 p.m.

Comment on mode of inheritance: Mode of inheritance for CHRND is biallelic for the fast-channel myasthenic syndrome (OMIM:616322) and AChR deficiency (OMIM:616323), and monoallelic for the slow-channel myasthenic syndrome (OMIM:616321).

Created: 26 Jan 2017, 3:52 p.m.

Comment on phenotypes: UKGTN test include CHRND on their panel for Myasthenic syndrome, slow-channel congenital, 601462.

Created: 26 Jan 2017, 3:46 p.m.

Green List (high evidence)

Mutations in CHRND can cause slow channel congenital myasthenic syndrome which is autosomal dominant and results in a gain of function; fast channel congenital myasthenic syndrome which is autosomal recessive; and AChR deficiency syndrome. The Acetylcholine receptor deficiency syndrome can mimic the deficiency syndrome due to mutations in RAPSN with episodic respiratory crises associated with infections a common feature.

Covered by the Oxford Congenital Myasthenia Service

Created: 24 Jan 2017, 4:59 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Slow channel myasthenic syndrome; fast channel myasthenic syndrome; Acetylcholine receptor deficiency syndrome

Publications

• PMID: 16916845
• PMID: 11782989
• PMID: 11435464

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