Cockayne syndrome is a rare autosomal recessive multisystem condition characterized by dwarfism, birdlike facies, premature aging, photosensitivity, progressive neurological dysfunction and intellectual deficit.
Patients who have the Cockayne Syndrome show the following :
This is seen during infancy but in many cases, the diagnosis is not made at this point.
Severe form of CS I is what brings about the presence of cataracts in children who are younger than 3 years of age. This shows a poorer prognosis and in many cases it leads to early death.
General delay in psychomotor development
All individuals with category I Cockayne Syndrome exhibit mental retardation. This delay in psychomotor development becomes very visible around the age when speech and walking are expected to start developing.
According to neurologic examination patients show abnormal gait coupled with increased or decreased muscle tone and reflexes . The abnormal gait is due to contractures of the ankles, knees and hips as well as leg spasticity and ataxia.
Another important characteristic of this disorder is pigmentary degeneration of the retina. Optic disk pallor and optic atrophy is also frequent. The changes in ophthalmology are often progressive.
Sensorineural hearing loss is present in more than 50% of patients with this condition. Dental caries is equally common as the root in permanent teeth of patients is often short . Photodermatitis which leads to dry scaly skin is seen in most patients. The aged appearance is as a result of this disease process.
In some patients, there is decreased creatinine clearance but this rarely requires medical treatment. Structural irregularities in the renal system are not regularly reported. Testicular hypoplasia or cryptorchidism affects more than 30% of male patients . Females menstruate but the cycles are not regular. Puberty is delayed in both sexes in certain cases.
In situations where patients are suspected to have CS, the first step taken by professionals is to establish baseline renal function and deal with possibility of other conditions with the help of routine laboratory tests .
Chromosome analysis is the next step taken so as to remove karyotypic abnormalities associated with growth failure. Chromosome breakage studies may come in if Bloom Syndrome is considered in the differential diagnosis . These studies coupled with mutation analysis are very important so as to remove the possibility of Bloom Syndrome or isolated xeroderma pigmentosum.
CT Scan and MRI scans can equally be used to search for white matter irregularities, cerebral atrophy, increased ventricular size and normal pressure hydrocephaly. Radiographs of the skeleton will also show vertebral body and pelvic abnormalities.
Other tests carried out include audiometry to determine sensorineural hearing loss, electroencephalography to look through any seizure activities and electroretinography to see if there are abnormalities in the electric potential of the retina.
Medical care is purely supportive and includes physiotherapy, photoprotection with sunscreens and clothing and hearing aids.
Genetically, the Cockayne Syndrome and subtypes is classified as follows:
Cockayne Syndrome is caused by the mutations in the ERCC6 and ERCC8 genes . These genes aid the repair of damaged DNA using the proteins they make, through the transcription-coupled repair mechanism. When the ERCC8 or ERCC6 gene is altered, DNA damage is not repaired. The accumulation of this damage is what results in the malfunctioning of cells and death of the cells.
According to the office of rare diseases, the Cockayne Syndrome is a rare condition. This means that less than 2 in 100,000 people have any of the CS subtypes. The CS I is panethnic and since the condition is an autosomal recessive disorder, the male to female ratio is 1:1.
With all types of Cockayne Syndrome, aging prematurely is a cardinal feature . The abnormality in growth and development become visible within the first two years of life. When the disease is at its peak, the head circumference, weight and height of the individual will be far below the fifth percentile.
The aging process is illustrated by bent standing posture, sunken eyes, thinning of the hair and skin and all the usual physical appearance of cachectic dwarfism. Additionally, there is an extensive and diffuse demyelination in both the central and peripheral nervous systems.
Basal ganglia and precapillary calcifications are visible at a very age. Acute neuronal loss in the cerebellum and cerebral cortex is also present. All of these are consistent with the physiological changes associated with aging.
There are no guidelines for prevention of Cockayne syndrome.
Cockayne Syndrome is a congenital autosomal recessive condition that has been categorized as rare. The common characteristics of this condition are stunted growth, under development of the nervous system, photosensitivity (abnormal sunlight sensitivity), progeria (fast paced aging) and early death .
The symptoms vary greatly in patients depending on the age at which the first signs appear. CS is part of a group referred to as the “leukodystrophies”. These are conditions which are characterised by the degeneration of white matter.
The disorder is basically a defect in the repair mechanism of DNA.
A couple known to be carriers of a single CS gene mutation has a 25% possibility of giving birth to a child with the Cockayne Syndrome condition. A child can only be affected by the condition if he inherits a mutation in a particular CS gene from the parents (both).
Since the symptoms of the Cockayne Syndrome vary significantly, the range of severity has been established by dividing the condition into three distinct types. They are as follows:
With this type of CS, the patient shows usual prenatal growth but at around one year of age, the developmental abnormalities begin to surface. Individuals with this CS type have an average lifespan of 10 to 20 years.
This CS type is known by the abnormalities and growth failure which begin at birth. Postnatal neurological development is poor and in many cases, absent. Individuals with this CS type have an average lifespan of 7 years.
This CS type sets in later than the previous two. It shows fewer symptoms and there is a slower rate of progression. There is no agreed average lifespan for people with this CS type but some patients live up to 50 years.
In some cases, the patient has a combination of Cockayne Syndrome and Xeroderma Pigmentosium. This is denoted by a variety of changes to the skin. Areas of skin exposed to sunlight may show mild freckling and in more severe cases, skin cancer.
Parents of the patient need to understand that treatment is symptoms-based and supportive. The neurologic and neurosensory abilities of the patient must be optimised in line with medical directions . Such parents must also undergo genetic counselling as having one CS child means that there is a 25% chance of giving birth to another child with the condition.