Cerebro-Oculo-Facio-Skeletal Syndrome (COFS, Pena Shokeir II Syndrome, Cockayne Syndrome Type II)

Cerebro oculo facio skeleteal syndrome is also known as COFS syndrome. It is a congenital genetic disorder that affects the brain and the spinal cord. This is a degenerative condition and is linked to Cokayne syndrome. It is an autosomal recessive inherited disorder, which was first described in 1974.

Symptoms of COFS syndrome

Commonly, this disorder is characterised by abnormal facial development. It is common for babies with this condition to have very small heads, small eyes and an abnormally large nose. Cataracts and blepharophimosis (a very narrow trench between the eyelids) are common features. Additional physical characteristics also include larger than average ears, a prominent philtrum (the furrow in the upper lip), a small jaw and an overlap between the upper and lower lips.

COFS also affects the limbs and it is common for the elbows and knees to be fixed in a stiff, bent position and the spine to be curved. The fingers may also be bent, a furrow might run from the top to the bottom of the sole of the foot, the heel may be prominent and the sole rounded (this is sometimes known as having rocker bottom feet). Babies with COFS syndrome may also have a higher risk of osteoporosis (brittle bones) and hip problems.

COFS syndrome also tends to affect growth and development and babies tend to ‘fail to thrive’. They grow slowly, struggle to feed normally and often display a lack of muscle tone. Children with COFS also often have a Simian crease. This occurs when the lines in the palm of the hand meet. Other characteristics include nipples being located far apart and a high risk of chest infections.

What is the prognosis for children with COFS syndrome?

The prognosis is poor. In most cases, as the condition is progressive, symptoms get worse with time and the average lifespan is just 3-7 years.

What causes COFS syndrome?

COFS syndrome is an inherited genetic condition, which means that it is passed on from parents to their children. As the syndrome is recessive, this means that you must inherit the defective gene from each parent in order to develop COFS syndrome. If you inherit just one gene, you will be a carrier, but you will not usually suffer from any symptoms. The inheritance pattern means that with each pregnancy, there is a 25 percent chance of the child having COFS syndrome in cases where both parents are carriers. There is a 50 percent chance of the child being a carrier and a 25 percent chance of the child having completely regular genes.

Research has suggested that COFS syndrome is linked to the genes responsible for attending to damaged DNA. Some that have been discovered include ERCC6, ERCC8 and ERCC2. Further research in this area is underway.

Who is affected by COFS syndrome?

COFS syndrome affects both females and males from all ethnic groups and symptoms are present at birth. This is a very rare syndrome and the exact number of cases in the UK is unknown.

Comparative disorders

Examples of disorders and conditions that cause similar symptoms to COFS syndrome include:

• Neu-Laxova syndrome: this rare autosomal recessive inherited disorder affects growth prior to birth and causes physical abnormalities such as a small head, external genitalia and structural problems affecting the limbs.
• Potter syndrome: also known as bilateral renal agenesis, Potter syndrome is a rare disorder that contributes to abnormal physical features including a beak-like nose, a small jaw, abnormal eyelids and eyes set wider apart than normal. This disorder also causes excessive skin growth and the skin looks and feels very dry. It is possible for the kidneys to be underdeveloped or for one to be missing. Young children may also have structural disfigurations, such as a club foot.
• Seckel syndrome (also known as nanocephalic or bird-headed dwarfism): this autosomal recessive inherited disorder causes low birth weight and delayed development. Other characteristics include a small head, a beak-shaped nose, wide-set eyes and numerous structural abnormalities affecting the thumb and fingers, the thigh bone, the feet and the spine.

How is COFS syndrome diagnosed?

Often, COFS syndrome is diagnosed based on physical symptoms present at birth. X-rays and genetic tests may also be carried out to confirm a diagnosis and differentiate between COFS syndrome and other, similar disorders.

Are there any treatments available?

Treatment is designed to ease symptoms and support children. Genetic counselling should be made available for parents.

Research into COFS syndrome is ongoing.