Congenital myaesthenic syndrome

Gene: CHRNG

Comment on phenotypes: Previous phenotypes:
Myasthenia gravis, neonatal transient;Neonatal congenital myasthenia;escobar syndrome;fetal akinesia deformation sequence syndrome/FADS;multiple pterygium syndrome/MPS

Created: 22 Mar 2021, 1:40 p.m. | Last Modified: 22 Mar 2021, 1:40 p.m.

Panel Version: 2.19

I don't know

PMID:16826520 (Hoffmann et al., 2006) conclude that Escobar syndrome is a prenatal myasthenia caused by disruption of the acetylcholine receptor fetal gamma subunit. AChRs have five subunits including two alpha, one beta and one delta. For the fifth subunit, gamma subunits are present in early development (switching to epsilon subunits in late fetal development).

Created: 10 May 2019, 11:15 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
Myasthenia gravis, neonatal transient; Neonatal congenital myasthenia; escobar syndrome; fetal akinesia deformation sequence syndrome/FADS; multiple pterygium syndrome/MPS

Comment when marking as ready: >3 unrelated cases of CHRNG causing Escobar syndrome and Multiple pterygium syndrome/MPS, characterized by muscle weakness.

Created: 2 Feb 2017, 11:27 a.m.

Comment on list classification: Updated rating from Red to Green: 1 Green review, confirmed link to Escboar syndrome on DD-G2P, >3 cases of CHRNG mutations causing Escobar syndrome. PMID:16826520 describe Escobar syndrome as a prenatal myasthenia.

Created: 2 Feb 2017, 11:26 a.m.

CHRNG is a confirmed DD-G2P gene for Escobar syndrome (OMIM:265000).

Created: 2 Feb 2017, 11:24 a.m.

Multiple pterygium syndrome (MPS, OMIM:253290) is a condition characterised by prenatal growth failure with pterygium and akinesia leading to muscle weakness and severe congenital contractures, as well as scoliosis. Escobar syndrome (OMIM:265000) is the non-lethal form of (lethal)MPS. >3 unrelated cases in varied populations of CHRNG subunits causing Escobar Syndrome (a prenatal myasthenia: see PMID:16826520).

Created: 2 Feb 2017, 11:24 a.m.

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

Created: 31 Jan 2017, 4:36 p.m.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neonatal congenital myasthenia; escobar syndrome; fetal akinesia deformation sequence; multiple pterygium syndrome

Publications

• PMID: 16826531
• PMID: 22167768
• PMID: 27245440
• PMID: 25411939

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