Paediatric or syndromic cardiomyopathy

Gene: CRYAB

Green List (high evidence)

Comment on list classification: There are at least five unrelated families reported with syndromic or early onset crdiomyopathy, particularly dilated cardiomyopathy. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 4 Sep 2026, 12:50 p.m. | Last Modified: 4 Sep 2026, 12:50 p.m.

Panel Version: 8.11

PMID:27904835 (2016) reported a Polish family with a 63-year-old female proband and three affected relatives (father and two others) with myofibrillar myopathy, cataract, and cardiomyopathy, all heterozygous for a novel dominant c.326A>C (p.Asp109Ala) variant in CRYAB gene identified by whole-exome sequencing and confirmed by Sanger sequencing; segregation confirmed in three affected relatives and absent in one unaffected relative and 86 ethnically matched controls, with structural modeling supporting pathogenicity.

PMID:28493373 (2017) reported a family with early-onset restrictive cardiomyopathy combined with skeletal myopathy, associated with the novel c.326A>G (p.Asp109Gly) variant identified via NGS gene panel.

PMID:32420686 (2020) reported a paediatric patient with childhood-onset congenital cataracts and myopathy (with cardiac involvement noted in the broader phenotypic spectrum), heterozygous for a novel c.514delG (p.Ala172ProfsTer14) frameshift variant identified by whole-exome sequencing.

PMID:38212463 (2024) reported two affected individuals in a parent-child pair: a 32-year-old proband with syndromic dilated cardiomyopathy (DCM) and congenital cataract, and his 10-year-old child with congenital cataract but no cardiomyopathy to date, both heterozygous for a novel stop-loss variant c.527A>G (p.Ter176TrpextTer19) identified via whole genome sequencing of a 159-patient DCM cohort; supports autosomal dominant transmission with incomplete penetrance for the cardiac phenotype at the child's current age.

PMID:42170542 (2026) reported a 16-year-old male with early-onset DCM and non-sustained ventricular tachycardia, heterozygous for a novel c.205C>T (p.Arg69Cys) variant identified by whole-exome sequencing and confirmed by Sanger sequencing, together with a PSEN2 variant of uncertain significance.

This gene has been associated with relevant phenotypes in OMIM (MIMs #615184 & #608810) and Gene2Phenotype (with definitive rating on the Cardiac panel) and these records were last accessed 04 September 2026).

Created: 4 Sep 2026, 12:47 p.m. | Last Modified: 4 Sep 2026, 12:47 p.m.

Panel Version: 8.7

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cardiomyopathy, dilated, 1II, OMIM:615184; dilated cardiomyopathy 1II, MONDO:0014073; Myopathy, myofibrillar, 2A, adult-onset, OMIM:608810; myofibrillar myopathy 2, MONDO:0012130

Publications

• 27904835
• 28493373
• 32420686
• 38212463
• 42170542

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

I don't know

OMIM#615184 Cardiomyopathy, dilated, 1II; OMIM# 613763 Cataract 16, multiple types; OMIM#608810 Myopathy, myofibrillar, 2; OMIM#613869 Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related

Created: 25 Mar 2019, 4:30 p.m.

Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes, Pua et al, Journal of Cardiovascular Translational Research, online Feb 2016 (doi:10._1007/_s12265-016-9673-5). The panel contains disease-causing, putatively pathogenic, research and phenocopy genes, and it is unclear from the publication whether this gene falls into the disease-causing category. No. of mutations indicated in supplemental table = 3. HGMD: 24 DM variants associated mainly with paeditaric cataracts though some patients can have cardiomyopathy and myopathy. Some truncating variants associated with cardiomyopathy. A number of variants have functional studies eg: Raju (2013) Biochem Biophys Res Commun 430: 107 PubMed: 23194663 of a variant assoc with cataracts, cardiomyopathy and myopathy. van der Smagt Clin Genet. 2014 Apr;85(4):381-5. doi: 10.1111/cge.12169: present a case of adult onset DCM.

Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

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