Dilated and arrhythmogenic cardiomyopathy

Gene: FKRP

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. Reviewers note that all cases except one were paediatric onset, and so this is too rare a cause of adult onset DCM (as presenting feature with no other features) to justify rating green on this panel. It should be added to R135 Paediatric or syndromic cardiomyopathy instead.

Created: 6 Dec 2024, 9:37 a.m. | Last Modified: 6 Dec 2024, 9:37 a.m.

Panel Version: 2.35

Green List (high evidence)

Comment on list classification: This gene should be considered for promotion to green rating in this panel in the next GMS review.

Created: 8 Dec 2023, 6:13 p.m. | Last Modified: 8 Dec 2023, 6:13 p.m.

Panel Version: 2.20

As reviewed by Oliver Watkinson, the limb-girdle muscular dystrophy phenotype caused by biallelic FKRP variants includes dilated cardiomyopathy as part of the phenotype.

PMID:32914449 reviewed 56 patients with limb-girdle muscular dystrophy and biallelic FKRP variants, of which 45% of patients had dilated cardiomyopathy as part of the phenotype with a median age of 54 years for patients homozygous for the common founder c.826C>A, compared to 18 years of age for other variants.

There were also a number of cases reported with dilated cardiomyopathy being the presenting condition and preceding overt skeletal muscle disease as noted by Oliver Watkinson including the recent case that he has seen in hospital.

Dilated cardiomyopathy was also reported as part of the LGMD phenotype in both OMIM (MIM #607155) and Gene2Phenotype.

Created: 8 Dec 2023, 6:05 p.m. | Last Modified: 8 Dec 2023, 6:11 p.m.

Panel Version: 2.17

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5, OMIM:607155

Publications

• 32914449

Green List (high evidence)

This gene causes limb girdle muscular dystrophy type 2i (AKA LGMDR9), which often has dilated cardiomyopathy as part of the phenotype (PMID 32914449). There are however a few reports of dilated cardiomyopathy being the presenting condition and preceding overt skeletal muscle disease (PMID 19705481, 18060779, 15833432). In my hospital we have recently found another 25yo patient who presented with dilated cardiomyopathy 5 years before overt skeletal muscular problems. Her initial DCM gene panel failed to identify the cause of her disease (we will try to wrote up her case in due course). With all this in mind this gene should be green on the R132 panel.

Created: 17 Nov 2023, 10:41 p.m. | Last Modified: 17 Nov 2023, 10:41 p.m.

Panel Version: 2.17

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Dilated cardiomyopathy; Limb girdle muscular dystrophy

Publications

• 32914449
• 19705481
• 18060779
• 15833432

I don't know

New gene submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Amber on this panel.

Created: 3 Dec 2019, 2:28 p.m. | Last Modified: 3 Dec 2019, 2:28 p.m.

Panel Version: 0.52