Rhabdomyolysis and metabolic muscle disorders

Gene: POC5

Green List (high evidence)

Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. Although rhabdomyolysis was only considered in one patient (P5 in PMID: 40590205), debilitating muscle pain/cramps (triggered by exercise and sometimes accompanied by elevated serum CK) represent a notable feature of the disorder which is best captured by this panel.

This disorder is relevant to the R381 Other rare neuromuscular disorders super panel, which will be applied through inclusion on this panel.

Created: 3 Sep 2025, 9:52 a.m. | Last Modified: 3 Sep 2025, 9:58 a.m.

Panel Version: 5.9

Total of 12 families reported in PMID:40590205 and PMID:29272404 with biallelic LOF variants in the POC5 gene presenting with retinal dystrophy (11/12), diabetes mellitus (10/12), lipodystrophy (6/12), kidney disease (7/12), and neuromuscular abnormalities (10/12) primarily comprising intermittent, involuntary painful muscle cramps (8/12). Muscle cramps arose in childhood and were often disabling and difficult to treat. Elevated serum CK levels were noted in 4 individuals.

Ten different variants identified with two variants found in multiple unrelated families from different ethnic and geographic backgrounds. Aberrant localization of POC5 at the basal body of the cilium, provides evidence that the described syndrome is a ciliopathy. Supportive zebrafish knockdown model.
Sources: Literature

Created: 3 Sep 2025, 9:43 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Retinal dystrophy; diabetes mellitus; lipodystrophy; renal failure; abnormal muscle physiology; muscle cramps

Publications

• 29272404
• 40590205