Cockayne Syndrome
Definition
Cockayne syndrome (CS) is a rare inherited disorder that results in an extreme sensitivity to ultraviolet (UV) irradiation, mental retardation, and precocious (premature) aging.
Description
Since first reported in 1936 by Dr. Edward A. Cockayne, less than 200 cases of this disorder have been documented in medical literature. At birth, newborns with CS may have microcephaly (small-sized head) and low birth weight. During the first year of life they do not feed well and, as a result, they suffer from growth failure and delayed development. Ultimately, the disease usually results in death during the teenage years.
Genetic profile
CS results from mutations in the CSA gene (also known as the ERCC8 gene) located on chromosome 5. An affected person has inherited one abnormal or nonworking gene from each parent, a pattern that is consistent with autosomal recessive inheritance. When functioning normally, the CSA gene helps cells remove and destroy deoxyribonucleic acid (DNA) errors from strands undergoing active transcription. Also, the CSA gene allows cells to synthesize ribonucleic acid (RNA) after exposure to UV light. Although the parents of an affected child are normal, each of them carries an abnormal gene for CS. Therefore, they have a 25% risk with each pregnancy of having another affected child.
Demographics
CS occurs in less than one in 250,000 births and does not affect any one ethnic group more than another. Males and females are equally affected.
Signs and symptoms
The symptoms of CS are very striking. Failure to grow begins during the first year of life and results in the appearance of dwarfism. The patient's weight is affected more than height. Also, some babies do not feed well and require feeding through a gastrostomy tube (a tube inserted through the abdominal wall into the stomach) to prevent malnutrition. As the infant grows, a delay in developmental milestones becomes apparent around the time that walking and talking should occur. Mental retardation in the mild to moderate range is found in all patients with CS. A small number of patients will have severe to profound mental retardation and some never have more than a few words of speech.
Other physical features include sun-sensitive skin, degeneration of retinal pigment, cataracts, and hearing loss. With exposure to sunlight, skin rashes appear and patients develop dry, scaly skin and thin hair. As part of the disease process, the skin develops an aged, leathery appearance. Although the eyes appear normal early in life, the retina later loses its pigment or color and develops a "salt-and-pepper" appearance. If cataracts appear within the first three years of life, the patient usually has the more severe form of CS that leads to death before adolescence. More than half the patients with CS have sensorineural hearing loss. The range of loss is from mild to severe.
Another finding of CS is an unusual gait (walk), caused by a combination of leg spasticity and contractures of the hips, knees, and ankles. The stooped posture often seen in CS results from kyphosis and joint contractures.
The most notable sign of CS is precocious senility (premature memory loss and confusion). Patients undergo neurological changes that resemble normal aging; the central and peripheral nervous systems lose myelin and neurons disappear from the central cortex and cerebellum. However, these changes occur at an extremely accelerated pace leading to death during early adolescence.
