Biallelic mutations in C2orf69 lead to a severe autosomal recessive inherited clinical picture. The main clinical features are congenital brain malformations, especially cerebellar atrophy and hypomyelination, which becomes evident during the course of the disease. Affected children are microcephalic and show a severe developmental delay, which may also be accompanied by other neurological disorders, including epilepsy and muscular hypotonia. Particularly characteristic of the clinical picture is the development of aseptic autoinflammations, especially in the joints, and the occurrence of organ dysfunctions, such as liver dysfunctions and hormone disorders, e.g. thyroid dysfunctions. The prognosis of the affected children is poor. Many die early in childhood in the course of fulminant autoinflammation and multi-organ failure.
C2orf69