Cockayne Syndrome is a rare genetic disorder otherwise known as Neil-Dingwall disease. At its core, it is an anomaly in the development of the nervous system, which is characterized by premature aging of a person, dwarfism, skin lesions, impaired vision and hearing.
Definition
Cockayne syndrome is an autosomal recessive neurodegenerative disease that appears as a result of a violation of the DNA repair mechanism. Such patients are weak, they are sensitive to light due to the pathology of the visual analyzer, they have disorders of the nervous system, as well as a violation of the development of one or all internal organs. Such changes are associated with rapid and extensive degradation of white matter.
Children with the condition typically live for about ten years, but there have been rare cases of them reaching adulthood. Scientists can name what specific changes in the genetic material are observed in this syndrome, but the relationship of damage and clinical manifestations remains a mystery.
Study history
Cockayne Syndrome is named after 20th-century English physician EdwardCockayne. He first encountered and described this disease in 1936. Ten years later, another of his articles was published, dedicated to this pathology.
The disease got its second name thanks to the work of two women: Maria Dingwall and Katherine Neill, who published their observations of twins with symptoms similar to those of Cockayne's patients. In addition, they drew parallels with another nosology - progeria, which is characterized by similar clinical manifestations.
Reasons
How does science explain the appearance of such a disease as Cockayne Syndrome? Its causes lie in damage to the loci of two genes - CSA and CSB. They are responsible for the structure of enzymes involved in the repair of damaged DNA.
There is a theory that defects only affect the repair of active genes. This statement may explain the fact that, despite the high sensitivity to ultraviolet light, people with this pathology do not get skin cancer.
There are also mixed forms of the disease, when the damage is also in the XPB locus (D or G). Then neurological symptoms join the main manifestations of the syndrome.
Shapes
Cockayne syndrome, based on the nature and location of gene damage, can be divided into four types.
- First type or classic. It is characterized by the birth of a morphologically normal child. Symptoms of the disease appear in the first couple of years of life. Hearing and vision deterioratethe peripheral, and then the central nervous system, begins to suffer first, up to atrophy of the cerebral cortex, although it is not as critical as in other forms. A person dies before reaching the age of twenty.
- The second type of pathology can be diagnosed already at birth. The neonatologist reveals a very weak development of the nervous system, the absence of obligatory reflexes and reactions to stimuli. Children die before the age of seven. This form is also known as Peña-Chocair syndrome. Patients experience a decrease in the rate of myelination and calcification of the nervous system.
- In the third type of the disease, all symptoms are much less pronounced, and their debut is observed later than in the first or second type. In addition, individuals with this lesion variant may survive to adulthood.
- Combined Cockayne syndrome. The genetic reason for this condition is due to the fact that in addition to damage to reparative enzymes, the child has a clinic of xeroderma pigmentosum.
Clinic
How is Cockayne's syndrome visually and symptomatically manifested? A photo of such children can shock especially impressionable women, and not all doctors can calmly contemplate them. The child has a growth retardation up to dwarfism with violations of the proportions between the trunk and limbs. The skin is pale, since sunlight is harmful to such patients, it gathers in wrinkles and folds, hyperpigmentation, scars and other signs of aging appear early. At the same time, they are quite resistant to hightemperatures, blisters and burns pass almost without a trace.
The eyes are large, sunken, there is visual impairment due to degenerative changes in the retina (in the form of s alt and pepper) and atrophy of the optic nerve. In some cases, retinal detachment along the periphery is possible. Eyelids do not close completely. Nystagmus is possible, that is, involuntary movements of the eyeballs from side to side or from top to bottom. In addition, accommodation paralysis is often observed when the pupils do not change their diameter. The child is deaf and has abnormalities in the structure of the cartilage of the auricles.
The cerebral part of the skull is poorly developed, the upper jaw is massive. Flexion contractures and other neurological disorders form in the joints. The child lags behind in intellectual development.
Diagnosis
Modern medicine cannot answer the question: who has Cockayne syndrome more often, since the mutation is point and predisposition to it can only be if a similar pathology has already been encountered in the family. But, as a rule, the parents of the proband are not aware of such precedents.
For confirmation, laboratory and instrumental diagnostics are carried out. In the general analysis of urine, you can see a slight protein content, in the blood there will be a decrease in thymus hormones, which are responsible for the growth and development of the child. An x-ray of the skull will show calcifications in the substance of the brain.
From specific studies, a biopsy of the sural nerve is used, which reveals a violation of myelination. When the patient's cells are irradiated with ultraviolet lightthere is an increased sensitivity to its effects. Studying the rate of DNA and RNA repair after damage can give a clearer picture of the disease.
For perinatal diagnosis, it is appropriate to use PCR to detect damaged genome structures.
Pathology
There are specific pathologies of the internal organs, according to which Cockayne's syndrome can be determined on the section. The causes of these changes are associated with a violation of the development of the neural tube in the prenatal period and the destruction of the nervous system after the birth of a child.
The autopsy pathologist discovers a disproportionately small brain, in which there are atherosclerotic altered vessels, as well as thickening of tissues due to their impregnation with calcium crystals and fibrin. The hemispheres appear mottled due to discoloration in demyelinated areas. There are also characteristic changes in the peripheral nervous system, in the form of conduction disturbances, proliferation of pathological glial cells.
Treatment
Specific treatment for this group of patients has not been developed. In order to avoid the birth of a child with a similar pathology, married couples who have risk factors should undergo medical genetic counseling before pregnancy. In addition, you can do an amniocentesis in the first three months of gestation to be sure of the baby's he alth.
To do this, it is enough to irradiate the cells in the amniotic fluid with a dose of ultraviolet radiation. If athe laboratory assistant reveals excessive sensitivity and lengthening of the recovery period, this indicates in favor of Cockayne's syndrome.
