The Cockayne syndrome It is a disorder of genetic origin that causes premature aging during childhood and adolescence. At the clinical level, it is characterized by a wide spectrum of alterations, including anomalies in growth and psychomotor development, neurological regression, characteristic physical phenotype, photosensitivity, ophthalmological and auditory anomalies, among others..
Regarding the etiological origin of Cockayne syndrome, most of the cases are mainly due to the presence of specific mutations in the ERCC8 and ERCC6 genes, located on chromosomes 5 and 10 respectively..
On the other hand, its diagnosis is confirmed through genetic study and RNA analysis, although it is essential to carry out a broad physical examination and study of the clinical characteristics of those affected..
Although there is no cure for this pathology, there are different symptomatological therapeutic approaches, based on medical and rehabilitative intervention: surgical correction, early stimulation, motor, electrostimulation, darmacological administration, physical therapy, etc..
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Cockayne syndrome was initially described by Cokayne in 1936. In his clinical report he referred to the description of two cases clinically defined by cachectic dwarfism, retinal atrophy and deafness.
In addition, he later expanded his descriptions with new clinically similar cases, whose symptoms began to develop clearly during early childhood.
Finally, around the 80s and 90s, thanks to technical advances, this pathology could be described at the cellular level, while in 1990 it was possible to identify the main genes involved in this pathology.
Cockayne syndrome is a rare disease of hereditary origin, the main manifestation of which is the development of premature aging. Although the severity of this condition can vary depending on medical complications, genetic abnormalities give rise to a series of manifestations compatible with premature aging and consequently, with a significant reduction in life expectancy..
Thus, in much of the medical literature, Cockayne syndrome is considered a type of segmental progeria. In general, the term progeria is used to refer to a group of diseases defined clinically by the presence of accelerated / premature aging in the child population.
These types of alterations are the product of genetic factors and tend to produce the physiological signs and symptoms of old age..
Cokayne syndrome is defined by three fundamental findings:
Different authors point out the presence of different clinical subtypes within Cokayne syndrome:
- Type I: This type is the classic and most frequent form of presentation of Cockayne syndrome. In this case, the cardinal symptoms tend to appear after 2 years of age..
- Type II: in this case, the clinical features appear early. Thus, it is possible to observe significant symptoms from birth, in addition they usually present a serious clinical status.
- Type III: This type is characterized by a milder clinical presentation. In addition, compared to the previous subtypes, it usually presents a late onset.
- Type XP / CS: a clinical subtype of Cockayne syndrome characterized by its joint presentation with xeroderma pigmentosa is distinguished. Its characteristics are defined by the development of short stature, mental retardation and skin cancer.
Cockayne syndrome is considered a rare or infrequent disease, with an estimated incidence of 1 case per 200,000 inhabitants in European regions.
Together, in the United States and Europe, Cockayne syndrome can present in about 2 or 3 cases per million births.
Regarding the sociodemographic characteristics of those affected, epidemiological investigations have not identified a higher frequency associated with sex, place of origin or ethnic and / or racial group.
Cockayne syndrome is characterized clinically by a heterogeneous pattern of clinical manifestations, all defined by a generalized deficit in development and severe multisystemic degeneration.
Some of the more common signs and symptoms in Cockayne syndrome usually include:
One of the most characteristic medical features of Cockayne syndrome is the presence of a slow or delayed development of physical growth.
Although, in some cases, it is possible to identify it in the prenatal stage, through routine pregnancy control ultrasound, it is more frequent to observe these parameters during the first years of life.
In general, in affected people it is possible to observe both a height and a weight below normal or expected for their sex and chronological age.
In addition, some clinical studies classify Cockayne syndrome as a form of dwarfism, that is, a growth disorder in which the adult height does not usually exceed 125cm.
On the other hand, as a consequence of generalized growth retardation, it is also possible to observe the presence of microcephaly. Thus, normally the head of affected individuals tends to be smaller or smaller than expected for their sex and age group..
The growth characteristics in Cockayne syndrome are defined by:
Cockayne syndrome is also often characterized by the development of different defining skeletal, muscular, and skin features:
The facial configuration is characterized as atypical due to the presence of a reduced size of the head, underdeveloped or narrow mouth and chin, and a hooked nose..
Likewise, the disposition of the teeth is usually abnormal, generating in a part of the cases malocclusion and the development of a significant number of cavities and anomalies in the mandibular projection.
Regarding the skin characteristics, it can be seen that the hair and skin have a dry and fine appearance. Generally, the skin presents an aged appearance with wrinkles, loss of adipose tissue or abnormal pigmentation.
On the other hand, in people who suffer from Cockayne syndrome it is possible to identify a disproportion in the size of their limbs, thus, it is common to observe abnormally large hands and feet, as well as longer arms and legs compared to the total size of the Body.
In addition, it is also possible that the joints develop abnormally, presenting a larger size than necessary and giving rise to a fixed position of different bone and muscle groups.
Regarding muscle alterations, the most common is to observe the development of spasticity, that is, an abnormal and pathological elevation of muscle tone, accompanied in some cases by the additional presentation of hypo or hyperreflexia (increased osteo-tendon reflexes).
The musculoskeletal characteristics of Cockayne syndrome are defined by the presence of:
The different sensory abnormalities that appear in Cockayne syndrome are fundamentally related to alterations in sensitivity to certain stimuli and the presence of ophthalmological and auditory pathologies.
One of the cardinal features of this pathology is the presence of photosensitivity, that is, an exaggerated sensitivity to light that can cause feelings of discomfort and pain. Thus, in many affected people it is possible to observe the development of burns and blisters when exposed to sunlight..
On the other hand, another typical medical finding is the development of ophthalmological and visual abnormalities, mainly related to retinal degeneration, the presence of cataracts, optic atrophy or progressive pigmentary retinopathy..
In addition, in terms of hearing ability, it is quite common to identify a significant loss of hearing (hearing loss) or the development of sensorineural deafness.
The sensory characteristics of Cockayne syndrome are defined by the presence of:
Regarding the neurological characteristics, it is possible to observe a generalized involvement of the central and peripheral nervous system, characterized by a progressive degeneration of the white and gray matter and the presence of cerebellar atrophy.
In general, individuals with Cockayne syndrome will present various features such as:
- Generalized intellectual deficit: both the incomplete development of some brain structures and subsequent cellular degeneration will lead to the presence of different cognitive deficits. All of these are fundamentally related to an intellectual performance below that expected for the age group of the affected person..
- Psychomotor retardation: Regarding the motor area, the development of different disorders related to ataxia, dysarthria in the presence of tremors will significantly hinder the acquisition of various skills. Affected people will present various alterations associated with the acquisition of standing, sitting, changes in posture, reaching for objects, etc..
- Language disorders: language skills are often poorly and incompletely developed. The language of people suffering from Cockayne syndrome is characterized by dysarthric speech, with the use of short sentences and few words.
The origin of Cockayne syndrome is found in the presence of genetic alterations, specifically in the development of mutations in the ERCC or CBS gene and the ERCC or CSA gene.
Both genes play a fundamental role in the production of proteins responsible for repairing damaged or damaged DNA. Faced with external or internal damage, DNA cannot be repaired normally and cells that show poor functioning will die exponentially..
Deficits in DNA repair can contribute to both photosensitivity characteristics and other typical clinical features of Cockayne syndrome..
Although the analysis of the medical history and the physical examination are essential to support the suspicion of Cockayne syndrome, the use of other types of medical approaches is essential.
In this case, the use of neuroimaging tests, such as magnetic resonance imaging or computerized tomography, are useful for determining neurological alterations..
In addition, the genetic study for the detection of anomalies in the repair of genetic alterations is essential for the definitive confirmation of the diagnosis of Cockayne syndrome.
Treatment of Cockayne syndrome and secondary medical complications is primarily symptomatic:
- Surgical intervention for musculoskeletal and dental abnormalities.
- Nutritional and food adaptations.
- Rehabilitative physical treatment: stimulation of psychomotor skills, control of spasticity and cerebellar disorders.
- Pharmacological treatment of spasticity.
- Postural adaptations.
- Muscle electrostimulation.
- Surgical and pharmacological treatment of ophthalmological anomalies
- Hearing adaptations.
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