Congenital myopathy

Gene: CNTN1

I don't know

Comment on list classification: Although there are two unrelated families reported with biallelic CNTN1 variants, myopathy was only reported in one. The siblings from the second family died after 3 and 5 days after birth. Both families were reported with fetal akinesia. There is also functional evidence available from cntn1 null mouse which showed progressive muscle weakness. Hence, this gene can only be rated amber on this panel with current evidence (one family and functional evidence).

Created: 28 May 2026, 4:13 p.m. | Last Modified: 28 May 2026, 4:13 p.m.

Panel Version: 7.36

PMID:19026398 (2008) reported four individuals from a consanguineous family of Egyptian descent with a lethal congenital myopathy characterised by secondary loss of β2-syntrophin and α-dystrobrevin from the muscle sarcolemma, central nervous system involvement, and fetal akinesia. The patients were identified with a homozygous thymidine duplication (c.871dupT) within exon 8 predicted to result in a reading frameshift introducing a premature stop codon (S291fsX296). There is also functional evidence available from cntn1 null mouse, which presented with ataxia, progressive muscle weakness, and postnatal lethality, similar to the affected members in this family.

PMID:32779773 (2020) reported two siblings presenting parentally with fetal akinesia and with homozygous deletion of exons 2-15 and 18-19. Other features included micrognathia and skin oedema in one, and pleural and pericardial effusions and skin oedema in the other. Both siblings had arthrogryposis and lung hypoplasia. The siblings died after 3 and 5 days after birth.

This gene has been associated with relevant phenotype in OMIM (MIM #612540, last accessed 28 May 2026).

Created: 28 May 2026, 4:03 p.m. | Last Modified: 28 May 2026, 4:14 p.m.

Panel Version: 7.36

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital myopathy 12, OMIM:612540

Publications

• 19026398
• 32779773

Removing the Q3_21_NHS_review tag. There are currently only 2 cases so amber is the appropriate rating.

Created: 1 Feb 2023, 5:17 p.m. | Last Modified: 1 Feb 2023, 5:17 p.m.

Panel Version: 3.14

I don't know

A second consanguineous family now reported with lethal congenital myopathy/FADS

Created: 10 Sep 2021, 1:22 p.m. | Last Modified: 10 Sep 2021, 1:22 p.m.

Panel Version: 2.56

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Fetal akinesia deformation sequence

Publications

• PMID: 32779773

I don't know

Gene rating and review submitted by Rachael Mein, Viapath Guy's Hospital February 2019 on on behalf of London South GLH for the GMS Neurology specialist test group.

Created: 30 Apr 2019, 10:09 a.m.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Myopathy, congenital, Compton-North, 612540

Publications

• 19026398

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

Green List (high evidence)

2 families reported with variants in this gene; severe phenotype with fetal akinesia and nonspecific myopathic features on skeletal muscle biopsy.

Created: 22 May 2026, 1:49 p.m. | Last Modified: 22 May 2026, 1:49 p.m.

Panel Version: 7.14

single family reported with CNTN1 variant.

Created: 30 May 2019, 4:40 p.m.

this is an interesting gene but not sure re strong evidence for this

Created: 6 Mar 2017, 12:14 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Myopathy, congenital, Compton-North, 612540

Publications

• 32779773
• 19026398

Red List (low evidence)

Comment on list classification: Expert contacted to see if there are additional cases to the single published to date. Amber and watchlist on current evidence.

Created: 7 Mar 2017, 2:39 p.m.

Comment when marking as ready: Insufficient evidence. One family

Created: 3 Feb 2017, 11:47 a.m.

Comment on list classification: Only one family identified to date

Created: 3 Feb 2017, 11:47 a.m.

Only one published family to date. Severe myopathy / myasthenic syndrome overlap. Currently insufficient evidence.

Created: 30 Jan 2017, 2:46 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Myopathy, congenital, Compton-North 612540

Publications

• PMID 19026398