Paediatric or syndromic cardiomyopathy

Gene: FKRP

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 11:50 a.m. | Last Modified: 24 Feb 2025, 11:50 a.m.

Panel Version: 6.7

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Gene has been reviewed initially on the Dilated and arrhythmogenic cardiomyopathy panel https://panelapp.genomicsengland.co.uk/panels/652/gene/FKRP/ but NHS GMS feedback was that it would be more suitable to be rated green on the Paediatric or syndromic cardiomyopathy panel.

Oliver Watkinson (NHS) review on the Dilated and arrhythmogenic cardiomyopathy panel:
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.

Achchuthan Shanmugasundram (Genomics England Curator) review on the Dilated and arrhythmogenic cardiomyopathy panel:
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: 6 Dec 2024, 10 a.m. | Last Modified: 6 Dec 2024, 10 a.m.

Panel Version: 6.3

I don't know

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

Created: 2 Dec 2019, 3:58 p.m. | Last Modified: 2 Dec 2019, 3:58 p.m.

Panel Version: 0.16