Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies

Gene: ANXA11

Green List (high evidence)

Comment on list classification: There is sufficient evidence available for the association of monoallelic variants in ANXA11 gene to limb-girdle syndrome. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 30 Sep 2025, 3:05 p.m. | Last Modified: 30 Sep 2025, 3:05 p.m.

Panel Version: 5.16

Comment on phenotypes: This gene has been associated with relevant phenotypes in OMIM (MIM #619733). OMIM was accessed on 30 September 2025.

Created: 30 Sep 2025, 3:02 p.m. | Last Modified: 30 Sep 2025, 3:02 p.m.

Panel Version: 5.15

PMID:34048612 (2021) reported 11 patients from three different Brazilian families presenting with three different phenotypes - Amyotrophic lateral sclerosis (ALS), inclusion body myopathy (hIBM), and ALS + hIBM. All the affected probands shared the same missense variant (c.118G>T/ p.Asp40Tyr) from ANXA11 gene. The patients had proximal muscle weakness of the upper and lower limbs with walking difficulties, scapular winging, and abdominal weakness, suggestive of a limb-girdle type of myopathy.

PMID:36134701 (2022) reported the identification of the same c.118G>T/ p.Asp40Tyr variant from ANXA11 gene in seven affected individuals from four large families from a relatively isolated island of Aegan Sea from Greece. Muscle weakness was first observed in all these patients in the third to fifth decade. The symptoms later progressed to proximal upper and lower limb weakness and distal lower limb weakness, All patients also presented with scapular winging.

PMID:36651622 (2023) reported a patient of Spanish descent with severe and rapidly progressive childhood-onset oculopharyngeal muscular dystrophy. The patient carried a different variant affecting the same Asp40 amino acid in ANXA11 gene (c.118_119delGAinsAT/ p.Asp40Ile). Progressive ptosis was noted in middle childhood, and Opthalmoparesis and neck flexor weakness appeared later but also in the first decade of life. From the age of 14, progressive axial and facial weakness was detected, as well as scapular winging and proximal and distal weakness, more pronounced in the lower extremities.

PMID:40730020 (2025) reported a 38-year-old Brazilian female patient with progressive limb weakness (more evident in proximal upper limbs and anterior compartment of the distal lower limbs), ophthalmoparesis, bilateral ptosis and bilateral scapular winging. She was identified with c.119A>T/ p.Asp40Val variant in ANXA11 gene.

The 'founder-effect' tag has been added as the same variant has been identified in multiple families from the same populations.
Sources: Literature

Created: 30 Sep 2025, 1:58 p.m. | Last Modified: 30 Sep 2025, 3:09 p.m.

Panel Version: 5.16

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Inclusion body myopathy and brain white matter abnormalities, OMIM:619733; inclusion body myopathy and brain white matter abnormalities, MONDO:0850514

Publications

• 34048612
• 36134701
• 36651622
• 40730020