He Fragile X syndrome (SXF) is one of the most common forms of intellectual disability of hereditary origin (Glover López, 2006).
At the genetic level, it is an X-linked pathology, which is why it is more commonly the male sex. Specifically, X syndrome Is due to a mutation of the FMR1 gene (Robles-Bello and Sánchez-Teruel, 2013).
At the clinical level, the most characteristic finding of fragile X syndrome is the presence of delayed or variable intellectual disability, from moderate to Grave (Molina, Pié Juste and Ramos Fuentes, 2010).
Accompanied, in addition, of the development of some characteristic physical signs, like extended face, Large external auditory halls or squint , Among others (from the Barrio del Campo, Zubizarreta and Buesas Casaus, 2016).
In addition, as part of its clinical course, it is possible to observe other types of alterations related to musculoskeletal, neurological, Cognitive and behavioral (from the Barrio del Campo, Zubizarreta and Buesas Casaus, 2016).
As for the diagnosis, it is usually performed based on the clinical findings (physical and neurological examination) along with the presence of a history Compatible with the condition of fragile X syndrome or a positive genetic study (Robles-Bello and Sánchez-Teruel, 2013).
At present, as in other diseases of genetic origin, a cure has not yet been identified. Although the therapeutic measures are oriented to the Treatment and compensation of the underlying deficits, there are some experimental approaches based on protein compensation.
Characteristics of fragile X syndrome
Fragile X syndrome is a genetic pathology that produces a wide variety of medical and cognitive complications, including delay Mental, learning problems, characteristic physical phenotype, etc. (Genetics Home Reference, 2016).
The first descriptions of the traits related to this syndrome go back to 1943, in the clinical reports of Martin and Bell. In them, Showed 11 cases within the same family, all characterized by the presence of mental retardation and some abnormal physical features. From this Form, an X-linked inheritance was suggested (Glover López, 2006).
In its initial moments, this medical condition was baptized with the name of Martin-Bell syndrome, in honor to its authors (Martin and Bell, 1943; Glover López, 2006).
It was not until 1969, when Lubs showed the actual existence of a significant correlation between the clinical features of this pathology and a Genetic alteration associated with a"fragility"of the X chromosome , At location q27.3 (Ferrando-Lucas, Banús Gómez and López Pérez, 2003).
In addition, in 1991, Verker and his team were able to identify the specific genetic defect underlying the X chromosome alteration, Consisting of a mutation of the FMR1 gene (Ferrando-Lucas, Banús Gómez and López Pérez, 2003).
On the other hand, in 1993 the molecular pattern of this pathology was precisely identified, an alteration of the FMRP protein encoded by the FMR1 gene. Specifically, poor production and / or absence leads to the development of the characteristic clinical picture of fragile X syndrome (del Barrio del Campo, Zubizarreta and Buesas Casaus, 2016).
Thus, alterations related to this genetic pattern are associated with severe multisystemic affection, in most of the affected individuals.
Although mental retardation is one of the cardinal clinical findings in fragile X syndrome, its clinical course is associated with a wide Variety of medical conditions, so the functional independence and quality of life of these people is often seriously deteriorated.
However, the life expectancy of people with fragile X syndrome is not generally different from that of the general population, as they do not Develop potentially life-threatening medical problems or complications (National Fragile X Foundation, 2016).
About us
Fragile X syndrome is considered one of the most frequent mental retardation disorders of genetic origin (National Institute of Child Health and Human Development, 2013), placing the second after Down syndrome.
Although this pathology may affect both sexes, as a consequence of its genetic pattern, it is much more prevalent in men than In women (Center for Disease Control and Prevention, 2015).
Although the number of people with this disease is not known exactly, different studies and institutions estimate that, around 1 child Male for every 5,000 births, has fragile X syndrome (Center for Disease Control and Prevention, 2015).
On the other hand, regarding the prevalence in the female sex, it is estimated that, for every 4,000 births, a case of fragile X syndrome In women (Seltzed et al., 2012).
In addition, a prevalence of this pathology associated with particular geographic regions or specific racial and / or ethnic groups has not been identified (National Human Genome Research Institute, 2013).
Signs and symptoms
Fragile X syndrome is a pathology that causes signs and symptoms associated with different areas (National Institute for Rare Disorders, 2010; Ribate Molina, Pié Juste, Ramos source, 2010; Of the District of the Field, Zubizarreta and Buesas Casaus, 2016):
Physical manifestations
Although the physical features are not specific and / or exclusive to this syndrome, we will now describe some of the most common findings in Individuals with fragile X syndrome:
- Craniofacial Malformations: One of the most common signs in fragile X syndrome are facial dysmorphisms. We can observe An elongated and narrow face with a broad forehead, large external auditory pavilions, prominent chin and thick lips with the inverted bottom.
- Musculoskeletal disorders: The development of weak muscle tone or hypotonia, abnormal increase in joint mobility (Articular hypermobility), flat feet or the presence of extremely fine cutaneous tissue are some characteristic features of X syndrome fragile.
- Ophthalmologic disorders: In the case of manifestations related to the eyes and visual capacity, strabismus or Misalignment of eyeballs are often the most frequent findings.
- Heart alterations: In most cases, individuals develop alterations related to aortic dilatation and Prolapse of the cardiac mitral valve.
- Endocrine disorders: In affected individuals it is possible to observe the development of an early or early puberty that, in the Males is characterized by the presence of a significant increase in testicle size (macroorchidism) and in women, due to the presence of Ovarian failure and / or early menopause.
Cognitive Manifestations
- Intellectual Disability: The most characteristic feature of fragile X syndrome is intellectual disability. However, all Individuals do not present the same degree of affectation. Generally, the male affected have a moderate intellectual delay, while In women it is mild.
- Generalized delay of learning: People with fragile X have a lower learning level and pace of learning Expected for their chronological age, fundamentally due to the presence of the rest of the cognitive manifestations.
- Speech disorders: In this area, the most striking is the delay in language acquisition. In addition, once purchased usually There are several deficits related to expressive language, the turn of speech or contextual language. Thus, it is possible to observe an absence of Social interaction or use of language in certain situations or contexts.
- Alteration of sensory integration: Some of the people affected usually show a marked difficulty to execute Activities and tasks related to discrimination and sensory integration. Thus, the ability to organize sensations, coordinate them, modulate them Or discriminate against them is often affected.
- Attention Disorders: It is possible to observe attentional deficits related to maintenance or alternation of this, in addition Is often associated with the presence of hyperactivity, so it is not strange to find cases of parallel diagnoses of fragile X syndrome and Disorder Of Attention Deficit Hyperactivity Disorder (ADHD).
Psychomotor manifestations
- Generalized delay of motor development: The presence of musculoskeletal disorders, such as muscular laxity or hypotonia since Early stages of life, hinders the acquisition of all or most of the skills related to motor activity.
- Delay in the acquisition of sedestation and walking: The ability to stay seated independently and autonomously is not usually Develop up to approximately 10 months, while the ability to walk and walk, does not develop before 20 Months.
- Fine motor impairment: A poor control of the musculature of the upper and lower extremities usually appears, Especially in the hands, because of this the manipulation of objects is often inadequate or deficient.
Behavioral Manifestations
- Poor social interaction: Usually avoid social interaction, present difficulties to maintain eye contact or Communicative protocols. In addition, they often use inappropriate language behaviors, such as pitch elevation, perseverance or usurpation of the Word shift.
- Poor self-regulation: Many situations can trigger episodes of anxiety Or nervousness, so they often need the Tracking routines.
- Defense behavior: Tactile defense is significantly prevalent in people with fragile X. Specifically, they avoid Physical contact or feel uncomfortable around other people.
Causes
This pathology is a medical condition associated with a disruption of the X chromosome (Genetics Home Reference, 2016).
The chromosomes carry the genetic information of each person and are located in the nucleus of the cells of the organism. Thus, humans We have 46 chromosomes, organized at a structural level in 23 pairs. In addition, within these, we have two chromosomes that will define our traits Sexual
Specifically, the male sex chromosome pair consists of an X and Y chromosome, whereas the female sex chromosome pair Is formed by two X chromosomes.
The combination and division of all this genetic material will determine our physical, cognitive and sexual characteristics. However, if during the In the embryonic development stage a failure occurs in the cell division that affects part or all of an X chromosome, the Fragile X syndrome.
In this pathology, therefore, a narrowing of the most distal part of the X chromosome has been identified, in the area Xq27.3 (Ribate Molina, Pié .
In addition, within each chromosome can exist infinidad of genes. Thus, in the case of fragile X syndrome, its clinical pattern is associated with a Mutation of the FMR1 gene (Genetics Home Reference, 2016).
This FMR1 gene is responsible for providing the essential biochemical instructions for the production of a protein called FMRP. Among other Functions, this protein is mainly responsible for the production of other components that play an essential role in the development of connections or Synapses , Between specialized nerve cells (Genetics Home Reference, 2016).
In this way, the absence or deficiency of the levels of this protein can alter the basic functions of the nervous system and, therefore, give Development of the characteristic clinical spectrum in Fragile X syndrome (Genetics Home Reference, 2016).
In addition, there have also been identified cases of fragile X syndrome in which there is a permutation, ie the genetic alteration is not complete, so good Some of them have an expected normal intellectual level for their age (Genetics Home Reference, 2016).
Diagnosis
The diagnostic suspicion of fragile X syndrome begins with Observation of some of the distinctive physical traits, however, When there is a family history compatible with this pathology is Diagnosis before birth.
As Fragile X syndrome has a genetic nature, employment Some prenatal tests such as amniocentesis or the Sampling of Chorionic villi, allow identification of the FMR1 mutation (Child Health and Human Development, 2013).
However, the most common is to observe the bells after birth and for So much, that the diagnosis is made during the infantile stage.
Usually, a physical and neurological examination is performed, accompanied Of a genetic study to determine the nature of the characteristics (Child Health and Human Development, 2013).
Treatment
The classic therapeutic approaches in fragile X syndrome are Constituted, mainly, by the medical attention, the education Special Cognitive stimulation , Speech therapy or programs Behavior modification and psychological care.
Although there is no cure for fragile X syndrome, they have been designed Numerous medical approaches for the treatment of symptoms and Complications derived from this pathology.
In addition, different clinical trials are currently underway Related to protein therapies, ie the supplement Pharmacological treatment of FMRP.
References
- CDC. (2015). Facts about Fragile X Syndrome. Obtained from Centers for Disease Control and Prevention.
- Del Barrio del Campo, J., Castro Zubizarreta, A., & amp; Buesa Casaus, L. (2016). Chapter VI. Fragile X syndrome. FEAPS.
- Ferrando-Lucas, M., Banús-Gómez, P., & amp; López-Pérez, G. (2003). Cognitive Aspects and Language in children with fragile X syndrome. Rev Neurol., 137-142.
- Glover López, G. (2006). 1. Historical Introduction. In G. d. -GIRMOGN, Fragile X Syndrome. Book Of consuclta for families and professionals.
- NFXF. (2016). Fragile X Syndrome. Retrieved from the Natoinal Fragile X Foundation.
- NIH. (2013). Fragile X Syndrome: Condition Information. Obtained from Child Health and Human Development.
- WORD. (2010). Fragile X Syndrome. Retrieved from the National Organization for Rare Disorders.
- Ribate Molina, M., Pié Juste, J., & amp; Ramos Fuentes, F. (2010). Fragile X syndrome. Protoc diagn Have pediatr., 85-90.
- Robles-Bello, M., &; Sánchez-Teruel, D. (2013). Treatment of X-chromosome syndrome Fragile from early care in Spain. Clinical and Health, 19-26.