COFS syndrome

Cerebro-oculo-facio-skeletal (COFS) syndrome, also known as Pena-Shokeir syndrome type II, is a rapidly progressive autosomal recessive neurodegenerative disorder that begins before birth. It belongs to a spectrum of nucleotide excision repair (NER) disorders and is considered by many experts to represent a severe form of Cockayne syndrome. COFS syndrome is caused by mutations in genes involved in DNA repair, most commonly ERCC6 (CSB), ERCC5, ERCC2, or ERCC1, which impair the cell's ability to repair UV-induced and oxidative DNA damage. The condition profoundly affects the central nervous system, eyes, face, and skeletal system. Key clinical features include congenital microcephaly, bilateral cataracts or microphthalmia, deeply set eyes, a prominent nasal root, micrognathia (small jaw), arthrogryposis (joint contractures), rocker-bottom feet, and severe failure to thrive. Neurological deterioration is marked, with progressive brain atrophy, absent or minimal psychomotor development, and hypotonia or hypertonia. Affected infants typically show intrauterine growth restriction and may have kyphoscoliosis and osteoporosis. The prognosis for COFS syndrome is very poor, with most affected children dying in early childhood, often before the age of five years. There is currently no curative treatment. Management is supportive and symptomatic, focusing on nutritional support (often via gastrostomy tube), management of contractures through physical therapy, and protection from sunlight due to the underlying DNA repair deficiency. Genetic counseling is recommended for affected families, and prenatal diagnosis may be available when the causative mutation has been identified.

Common questions about COFS syndrome