COL4A2 -Related Disorder Presenting in Adulthood With Rhabdomyolysis

The alpha 1 and 2 chains of type IV collagen, encoded by the COL4A1 (MIM 120130) and COL4A2 (MIM 120090) respectively, play essential roles in the vascular basement membranes. Pathogenic variants in COL4A1/ COL4A2 are associated with autosomal dominant cerebral angiopathies. The clinical manifestations of COL4A1/COL4A2-related disorders include: aneurysms, intracerebral hemorrhage, polymicrogyria, porencephaly, heterotopia, periventricular leukomalacia, epilepsy, and neurodevelopmental disorders. COL4A1 pathogenic variants that are in exons 24 and 25 have been associated with hereditary angiopathy, nephropathy, aneurysms, and cramps. The multisystemic phenotypes of COL4A1/COL4A2-related disorders are increasingly being studied. Animal models have suggested that COL4A2-related disorders may also manifest with a variable combination of multisystemic abnormalities affecting the eyes, muscles, and kidneys. Okano and colleagues recently reported a case of recurrent episodes of rhabdomyolysis in a 2-year-old with COL4A1-related disorder raising fundamental questions on mechanisms of COL4A1/COL4A2 variants in muscle homeostasis. To date, rhabdomyolysis has not been associated with COL4A2-related disorder in humans. Rhabdomyolysis is a medical emergency, where there is elevated creatine kinase (CK) level in the blood and increased excretion of myoglobin in urine, due to skeletal muscle damage and release of intracytoplasmic proteins into systemic circulation. Rhabdomyolysis is a serious medical condition. It require intensive care management due to an increased risk of some life-threatening complications [including disseminated intravascular coagulation, renal failure, and severe hyperkalemia]. Herein, we report a case of rhabdomyolysis in an adult with COL4A2-related structural brain malformations (including polymicrogyria and heterotopia).