Limb-Girdle Muscular Dystrophy and Distal Myopathy

Gene: DOK7

Green List (high evidence)

Association with congenital myasthenia: Over 30 unrelated families reported with bi-allelic variants. Note recent report of mild adult-onset disease and heterozygous variant PMID 32360404.

Association with FADS: Two families reported with this phenotype, severe end of the spectrum for DOK7-related disorders.

Created: 13 Jun 2021, 8:34 a.m. | Last Modified: 13 Jun 2021, 8:34 a.m.

Panel Version: 0.7961

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Myasthenic syndrome, congenital, 10, MIM# 254300; Fetal akinesia deformation sequence 3, MIM# 618389

Publications

• 16917026
• 18626973
• 20147321
• 16794080
• 31453852
• 29395672
• 32360404
• 19261599
• 31880392

Green List (high evidence)

PMID: 31453852 - two adult patients with PTC variants and severe proximal muscle weakness with childhood onset. Condition is described as limb girdle myasthenia. Patient 1 had shoulder abduction and severe weakness of the pelvic girdle, patient 2 had muscle biopsy reveal muscle fibre II atrophy.

PMID: 32360404 - one adult patient with late onset atypical limb-girdle pattern of muscle weakness. Biopsy of deltoid muscle shows no features of MD.

PMID: 18626973 - 16 patients report proximal limb weakness, where 10 report neonatal onset.
Sources: Expert list

Created: 1 Jul 2020, 2:09 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Myasthenic syndrome, congenital, 10 254300

Publications

• PMID: 31453852
• 32360404

Green List (high evidence)

DOK7 is not a congenital myopathy per say, but frequently presents with a limb girdle phenotype. Affected patients may have investigations for limb girdle muscular dystrophies or congenital myopathies and so it should be included on a myopathy panel. Importantly in some patients it is treatable with salbutamol.

Created: 15 Jun 2020, 10:23 a.m. | Last Modified: 15 Jun 2020, 10:24 a.m.

Panel Version: 0.207

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital myasthenic syndrome type 10 - Limb Girdle Phenotype

Publications

• https://www.ncbi.nlm.nih.gov/pubmed/16794080
• https://www.ncbi.nlm.nih.gov/pubmed/18626973

Green List (high evidence)

Comment on list classification: Variable age of onset, that includes adult onset

Created: 24 Feb 2020, 5:10 a.m. | Last Modified: 24 Feb 2020, 5:10 a.m.

Panel Version: 0.37

>3 unrelated cases reported with myopathic changes in muscles.
Sources: Expert Review

Created: 24 Feb 2020, 5:09 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Myasthenic syndrome, congenital, 10 MIM#254300

Publications

• 31561939
• 31449669