Cerebrooculofacioskeletal Syndrome (COFS) is a lethal and rapidly progressive disorder, involving neuromuscular defects. Characteristic clinical features are numerous and include facial (low set ears, a sloping forehead, abnormally small head and jaws, and a prominent nasal bridge), ocular (deep set eyes, small eyes, cataract, nystagmus and other vision impairments, involuntary eye movements) neurological (hypotonia, moderate to severe mental retardation, and multiple joint contractures) and skeletal (osteoporosis, kyphoscoliosis, camptodactyly, and coxa valga among others) abnormalities. Respiratory infections are frequent. These symptoms present at birth, or are evident, at the most, by a few weeks of age. Clinical symptoms of COFS appear very similar to those of Cockayne Syndrome, and in fact, many geneticists are of the opinion that COFS is a part of the spectrum of Cockayne Syndrome.
The condition can be diagnosed prenatally through transabdominal ultrasound analysis. Differential diagnoses include Cockayne Syndrome (CS), Pena-Shokeir Syndrome I, Multiple Pterygium Syndrome, and Seckel Syndrome. However, the condition can be differentiated from CS by the presence of extensive calcifications in the brain and evidence of brain atrophy in CT scans. Respiratory complications of the condition are the most serious aspects, and most infants usually succumb to these before reaching five years of age. Treatment can only be supportive and is aimed at reducing the severity of the symptoms. Affected children may need a feeding tube.
COFS1 is caused by mutations in the ERCC6 (Excision Repair Cross-complementing Rodent Repair Deficiency, Complementation Group 6) gene. This is the same gene that is responsible for Cockayne Syndrome 2. The protein coded for by this gene is presumed to have a DNA or RNA unwinding function, and is involved in the preferential repair of active genes. It is not clear how these mutations exactly work towards the development of COFS1.