Cerebro-oculo-facio-skeletal (COFS) syndrome is a genetic degenerative disorder of the brain and spinal cord that begins before birth. The disorder is characterized by growth failure at birth and little or no neurological development, structural abnormalities of the eye and fixed bending of the spine and joints. Abnormalities of the skull, face, limbs and other parts of the body may also occur. COFS syndrome is inherited as an autosomal recessive genetic trait. COFS is now considered to be part of the spectrum of disorders within Cockayne syndrome.
Cerebro-oculo-facio-skeletal syndrome was first described in 1974. Symptoms of this disorder include unusual craniofacial features. These may include an extremely small head (microcephaly), an unusually prominent nose, abnormally small eyes, clouding of the eye’s lens (cataract), and a horizontally narrow opening between the eyelids (blepharophimosis). The ears are abnormally large, the upper lip overlaps the lower, the groove in the upper lip (philtrum) is abnormally long, and the jaw is unusually small (micrognathia).
In most patients, fixed bending of the elbows and knees (flexion contractures), a hunched back (kyphosis), and bending of one or more fingers (camptodactyly) occurs. Infants with cerebro-oculo-facio-skeletal syndrome usually have so-called “rocker bottom” feet and a groove over the length of the soles of the feet. A deformity of the hip (coxa valga) and porous bones (osteoporosis) may also occur.
Other features of this disorder include wide-set nipples, failure to thrive, slowed growth (developmental retardation), lack of muscle tone (hypotonia), feeding difficulties and one line in the palm of the hand formed by fusion of the usual two lines (simian crease). Children with cerebro-oculo-facio-skeletal syndrome have an increased vulnerability to respiratory infections.
Individuals with COFS syndrome show progressive deterioration and rarely survive beyond seven years.
Cerebro-oculo-facio-skeletal syndrome is an autosomal recessive genetic disorder. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
COFS syndrome has been found to be associated with mutations in genes responsible for repairing DNA damage. These genes are called excision repair cross-complementing genes and include ERCC6, ERCC8 and ERCC2.
Cerebro-oculo-facio-skeletal syndrome is a very rare disorder present at birth. It affects males and females and occurs in many ethnic groups.
The diagnosis of COFS syndrome is often made based on physical features seen at birth. X-ra. studies may reveal displacement of the small foot bones between the ankle and toes (second metatarsals) and neuroimaging studies may show reduced white matter with gray matter mottling. DNA repair studies on skin fibroblast cells may help to confirm a diagnosis of COFS syndrome. Molecular genetic testing to identify mutations in the excision repair genes is available on a research basis only.
Treatment of COFS syndrome is symptomatic and supportive. Genetic counseling is recommended for families of children with the disorder.
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