He Cockayne's syndrome (SC) is a disorder of genetic origin that causes premature aging during the infant and / or adolescent stage (Iyama and Wilson, 2016)
At the clinical level, Cackayne's syndrome is characterized by a wide spectrum of abnormalities, including abnormalities in growth and Psychomotor development, neurological regression, characteristic physical phenotype, photosensitivity, ophthalmological and auditory abnormalities, among others (Bayón Calatayud, Urdiales Urdiales, Atienza Delgado, Morante del Blanco, 2005).
As to the etiological origin of Cockayne's syndrome, a good part of the cases are due mainly to the presence of specific mutations in the Genes ERCC8 and ERCC6, located on chromosomes 5 and 10, respectively (Laugel, 2013).
On the other hand, the diagnosis of Cokayne Syndrome is confirmed through genetic study and RNA analysis, although it is essential to perform An extensive physical examination and study of the clinical characteristics of those affected (Dollfus and Laugel, 2009).
Although there is no cure for this pathology, there are different therapeutic approaches symptomatic, based on medical intervention and Rehabilitative: surgical correction, early stimulation , Motor, electrostimulation, darmacological administration, physical therapy, etc. Bayon Calatayud, Urdiales Urdiales, Atienza Delgado, Morante del Blanco, 2005).
Characteristics of Cockayne's Syndrome
He Cockayne's syndrome ( SC ) Is a rare disease of hereditary origin, whose fundamental manifestation is the Development of premature aging (Iyama and Wilson, 2016)
Although the severity of this condition may vary depending on medical complications, genetic abnormalities give rise to a number of Manifestations compatible with premature aging and, consequently, with a significant reduction in life expectancy (Iyama and Wilson, 2016).
Thus, in much of the medical literature, Cockayne syndrome is considered a type of segmental progeria (Iyama and Wilson, 2016).
In general, the term progeria is used to refer to a group of diseases defined at the clinical level by the presence of aging Accelerated / premature infant mortality (National Institutes of Health, 2015).
These types of alterations are the product of genetic factors and have to produce the physiological signs and symptoms characteristic of old age (Genetics Home Reference, 2016).
Thus, Cockayne's syndrome was first described by Cokayne in 1936. In his clinical report he referred to the description of two cases
Defined clinically by cachectic dwarfism, retinal atrophy and deafness (Laugel, 2013).
In addition, he later expanded his descriptions with new clinically similar cases, whose symptoms began to develop in an obvious way During early childhood (Laugel, 2013).
Finally, around the 1980s and 1990s, thanks to technical advances, this pathology could be described at the cellular level, whereas in 1990, We were able to identify the main genes involved in this pathology (Laugel, 2013).
In this way, Cokayne's syndrome is defined by three fundamental findings (National Organization for Rare Disroders, 2016):
1. Significant growth retardation (short stature, low weight, etc.).
2. Abnormally exaggerated sensitivity to light stimuli (photosensitivity).
3. Aged physical appearance.
In addition, different authors point out the presence of different clinical subtypes within the Cokayne syndrome (Conchello-Monleón et al., 2012; Lanzafame, Vaz, Nardo, Botta, Orioli and Stefanini, 2013; Laugel, 2013):
- Type I : This type is the classic and more frequent presentation of Cockayne syndrome. In this case, cardinal symptoms Have to appear after 2 years of age.
- Type II : In this case, clinical features appear early. Thus, it is possible to observe significant symptoms The birth, also usually present a serious clinical status.
- Type III : This type is characterized by a lighter clinical presentation. In addition, in comparison with the previous subtypes, Late start.
- Type XP / CS : A clinical subtype of Cockayne's syndrome characterized by the joint presentation with the Xeroderma Pigment. Its characteristics are defined by the development of reduced stature, mental retardation and skin cancer.
About us
Cockayne syndrome is considered a rare or rare disease, with an estimated incidence of 1 case per 200,000 inhabitants in regions (Dollfus and Laugel, 2009).
Together, in the United States and Europe, Cockay syndrome can occur in about 2 or 3 cases per million births (Genetics Home Reference, 2016).
With regard to the sociodemographic characteristics of those affected, epidemiological investigations have not identified a higher frequency Gender, place of origin or ethnic and / or racial group (National Organizadion for Rare Disroders, 2016).
Characteristic signs and symptoms
Cockayne syndrome is characterized clinically by a heterogeneous pattern of clinical manifestations, all of which are defined by a deficit Generalized in development and severe multisystemic degeneration (Iyama and Wilson, 2016)
Thus, some of the most common signs and symptoms in Cockayne syndrome usually include (Bayón Calatayud, Urdiales Urdiales, Atienza Delgado, Morante Del Blanco, 2005; Genetics Home Reference, 2016; National Organization for Rare Disorders, 2016):
to) Growth Delay
One of the most characteristic medical features of Cockayne syndrome is the presence of slow or slow growth of physical growth.
Although, in some cases, it is possible to identify it in the prenatal stage, through the Ultrasound Routines of pregnancy control is more Frequent observation of these parameters during the first years of life.
In general, in the affected individuals it is possible to observe both height and weight below normal or expected for their sex and age Chronological
In addition, some clinical studies classify Cockayne's syndrome as a form of dwarfism (Conchello-Monleón et al., 2012), ie a disorder Of growth in which adult height does not usually exceed 125cm (National Institutes of Health, 2016).
On the other hand, as a consequence of generalized lag of growth, it is also possible to observe the presence of Microcephaly . Thus, the Head of affected individuals is usually smaller or smaller than expected for their sex and age group (Center for Disease Control And Prevention, 2016).
Thus, the growth characteristics in Cockayne's syndrome are defined by:
- Under weight.
- Reduced size, compatible with the diagnosis of growth disorder or dwarfism.
- Microcephaly
B) Musculoskeletal disorders
Cockayne's syndrome is also characterized by the development of different skeletal, muscular and cutaneous features:
Thus, the facial configuration is characterized as atypical due to the presence of a reduced size of the underdeveloped head, mouth and chin or Narrow and hooked nose.
Also, the disposition of the dental pieces is usually abnormal, generating in a part of the cases malocclusion and the development of a number Of caries and anomalies in the mandibular projection.
As for the skin characteristics, it can be observed that the hair and the skin present a dry and fine appearance. Generally, the skin has a Aging appearance with wrinkles, loss of adipose tissue or anomalies in pigmentation.
On the other hand, in people suffering from Cockayne syndrome it is possible to identify a disproportion in the size of their limbs, thus, it is habitual Observe both abnormally large hands and feet, such as longer arms and legs compared to total body size.
In addition, it is also possible that the joints develop abnormally, presented a larger size than necessary and giving rise to a position Fixation of different bone and muscle groups.
On the other hand, regarding the muscular alterations, the most frequent is to observe the development of Spasticity , Ie an abnormal rise and Muscle tone, accompanied in some cases by the additional presentation of hypo or hyperreflexia (increased reflexes
Osteo-tendinous).
Thus, the musculoskeletal characteristics of Cockayne's syndrome are defined by the presence of:
- Atypical facial configuration.
- Dental malocclusion.
- Skin aging.
- Anatomic disproportion in upper and lower extremities.
- Development of spasticity and hyper / hyporeflexia.
C) Sensory disturbances
The different sensory abnormalities that appear in Cockayne's syndrome are mainly related to alterations in sensitivity To certain stimuli and the presence of ophthalmological and auditory pathologies.
In this way, 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 it is possible to observe the development of burns and blisters on exposure to sunlight.
On the other hand, another typical medical finding is the development of ophthalmological and visual anomalies, fundamentally related to degeneration Retinal detachment, the presence waterfalls , Optic atrophy or progressive pigmentary retinopathy.
In addition, in terms of hearing capacity, it is quite common to identify a significant loss of hearing loss ( Hearing loss ) Or the development of a Deafness of sensorineural nature.
Thus, the sensorial characteristics of the Cockayne syndrome are defined by the presence of:
- Photosensitivity.
- Ophthalmological pathologies.
- Hearing deficits.
(D) Neurological degeneration
As regards the neurological characteristics, it is possible to observe a generalized affectation of the central and peripheral nervous system, characterized by A progressive degeneration of white matter, gray and presence of cerebellar atrophy.
In general, individuals with Cockayne's syndrome will present different traits such as:
- Generalized intellectual deficit : Both incomplete development of some brain structures such as cellular degeneration Later, will lead to the presence of different cognitive deficits.
All these are mainly related to an intellectual performance below the expected for the age group of the Affected person.
- Psychomotor retardation : In the motor area, the development of different disorders related to the ataxia , Dysarthria at the Presence of tremors will significantly hinder the acquisition of various skills.
Thus, the affected people will present various alterations associated with the acquisition of standing, sitting, changes of posture, scope Of objects, etc.
- Disorders of speech : Language skills tend to be poor and incomplete. The language of the people who Cockayne's syndrome sufferers are characterized by dysarthric speech, using short sentences and few words.
Causes
The origin of Cockayne syndrome is found in the presence of genetic alterations, specifically in the development of mutations in the ERCC gene or CBS and the ERCC or CSA gene (Genetics Home Reference, 2016).
Both genes have a fundamental role in the production of proteins responsible for the repair of DNA Injured or damaged. Thus, in the case of external DNA can not be repaired normally, and cells with deficient functioning will die exponentially (Genetics Home Reference, 2016).
Thus, deficits in DNA repair can contribute to the characteristics of photosensitivity as well as to other typical clinical features of the Cockayne's syndrome.
Diagnosis
Although the analysis of medical history and physical examination are fundamental to support the suspicion of Cockayne's syndrome, it is The use of other types of medical approaches.
In this case, the use of neuroimaging tests, such as magnetic resonance imaging or Computed tomography Are useful for the determination of Neurological disorders (National Organization for Rare Disorders, 2016).
In addition, the genetic study for the detection of anomalies in the repair of genetic alterations is fundamental for the definitive confirmation of the Diagnosis of Cockayne's syndrome (Dollfus and Laugel, 2009).
Is there treatment?
The treatment of Cockayne's syndrome and secondary medical complications is mainly symptomatic (Bayón Calatayud, Urdiales Urdiales, Atienza Delgado, Morante del Blanco, 2005):
- Surgical intervention of musculoskeletal and dental anomalies.
- Nutritional and food adaptations.
- Physical rehabilitation treatment: stimulation of psychomotor skills, control of spasticity and cerebellar disorders.
- Pharmacological treatment of spasticity.
- Postural adaptations.
- Muscle stimulation.
- Surgical and pharmacological treatment of ophthalmologic anomalies
- Hearing adaptations.
References
- Bayón Calatayud, M., Urdiales Urdiales, J., Atienza Delgado, R., & Morante del Blanco, M. (2005). Cockayne Syndrome: treatment and rehabilitation. TO
Purpose of a case. Rehabilitation (Madr) , 171-5. Obtained from Rehabilitation (Madr). - Conchello-Monleón et al. (2012). Cockayne syndrome: a new mutation in the ERCC8 gene. Rev Neurol.
- Dollfus, H., & Laugel, V. (2009). Cockayne's Syndrome . Obtained from Orphanet.
- Iyama, T., & Wilson, D. (2016). Elements That Regulate the DNA Damage Response of Proteins Defective in Cockayne Syndrome. J Mol Biol ( 62-76).
- Lanzafame, M., Vaz, B., Nardo, T., Botta, E., Orioli, D., & Stefanini, M. (2013). From laboratory tests to functional characterization of Cockayne Syndrome. Mechanisms of Aging and Development , 171-179.
- Laugel, V. (2013). Cockayne syndrome: The expanding clinical and mutational spectrum. Mechanisms of Aging and Development , 161-120.
- NIH. (2016). Cockayne syndrome . Retrieved from the Genetics Home Reference.
- NIH. (2016). Dwarfism . Obtained from MedlinePlus.
- NORD. (2016). Cockayne Syndrome . Retrieved from the National Organization for Rare Disorders.