Congenital myopathy

Gene: PNPLA2

Red List (low evidence)

Comment on list classification: The average age of onset for Neutral lipid-storage disease with myopathy is around 30 years old. Among childhood-onset patients, many do not initially present with myopathy. Based on the available evidence, this gene is not in scope of the Congenital myopathy panel and should remain Red.

Created: 30 Oct 2025, 5 p.m. | Last Modified: 30 Oct 2025, 5 p.m.

Panel Version: 6.38

Biallelic mutations in PNPLA2 are associated with Neutral lipid-storage disease with myopathy, OMIM:610717 (NLSDM) - phenotype accessed 30th Oct 2025).

PMID: 37620213 Fu et al., 2023 - literature review
11 childhood-onset and 82 adult-onset patients; only 6/11 childhood onset patients presented with muscle weakness. NLSDM is often diagnosed by presence of Jordan's anomaly on a peripheral blood smear and elevated CK - some cases asymptomatic until later life. Age of disease onset in the childhood cases ranged from shortly after birth to 11yo. However, the onset of myopathy occurred several years after the initial symptoms in all individuals (between 3-33 years after initial symptoms).

PNPLA2 is already Green on the Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies panel.

Created: 30 Oct 2025, 4:57 p.m. | Last Modified: 30 Oct 2025, 5:01 p.m.

Panel Version: 6.38

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neutral lipid-storage disease with myopathy, OMIM:610717

Publications

• 21544567
• 37620213
• 40919432

Green List (high evidence)

variants in this gene have now been reported in young individuals presenting with progressive skeletal myopathy, raised CK, and sometimes cardiomyopathy and liver dysfunction. these findings suggest that variants in this gene can be associated with an early onset form of myopathy, supporting green rating of this gene.

Created: 19 Sep 2025, 10:47 a.m. | Last Modified: 19 Sep 2025, 10:47 a.m.

Panel Version: 6.35

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neutral Lipid Storage Disease with Myopathy; Neutral lipid storage disease with myopathy, 610717

Publications

• PMID: 21544567
• PMID: 40919432
• PMID: 37620213

Red List (low evidence)

Comment when marking as ready: Not in age range for inclusion on this panel

Created: 3 Feb 2017, 11:03 a.m.

Comment on list classification: Adult phenotype

Created: 3 Feb 2017, 11:02 a.m.

Information to date suggests adult onset (approx. 3rd decade) therefore not appropriate for congenital myopathy panel.

Created: 26 Jan 2017, 2:56 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neutral lipid storage disease with myopathy 610717

Publications

• PMID 21544567