Cockayne Syndrome: Two Siblings with Neurodegenerative Disease and Infection-Associated Deterioration

Background: Cockayne syndrome is a rare genetic autosomal-recessive disorder, characterized by a wide variety of nervous system abnormalities. The underlying mutations are located on genes ERCC6/CSB (10q11) and ERCC8/CSA (5q12.1), leading to defects in transcription-coupled DNA-repair.

Methods/Results: We present two siblings of consanguineous healthy parents from Turkey, who showed progressive neurodevelopmental delay, after having had a normal development over the first months of their lives. On clinical examination reduced muscle tone, lack of strength and ataxia with intention tremor and nystagmus were the most impressive findings. Further deterioration with altered states consciousness and loss of skills were reported in the course of mild infections. Diagnostic work-up showed next to pathological MRI with delayed myelination and later on hydrocephalus ex-vacuo with shrinkage of brain substance, a reduced activity of complex I of the mitochondrial respiratory chain. Thus, a mitochondrial disease was suspected and the patients were started on a supportive therapy with Riboflavin. The multigene panel testing for ataxia revealed a homozygous ERCC6-stop mutation. This was classified as most likely pathogenic and Cockayne syndrome subsequently was diagnosed.

Conclusion: In recent literature, mitochondrial dysfunction was proposed as a sign of Cockayne syndrome. In our case clinical features as well as the result of muscle biopsy implicated mitochondrial involvement. The possible underlying pathogenetic relations remain unclear for now, as well as the question if this offers a potential therapeutic target for patients with Cockayne syndrome.