He Seckel syndrome Is a congenital disease characterized by the presence of dwarfism and intrauterine growth retardation that extends to the postnatal stage (Baquero Álvarez, Tobón Restrepo and Alzate Gómez, 2014).
At the etiologic level, Seckel syndrome has an autosomal recessive genetic origin, associated with different specific mutations and different pathological variants, such as those located on chromosome 3, chromosome 18 or chromosome 18 (National Organization for Rare Disorders , 2007).
On the other hand, at the clinical level, Seckel syndrome is distinguished by the development of microcephaly, myogeny, low stature or particular facial appearance (Bird profile). In addition, all these traits are usually accompanied by severe retardation of intellectual development.
As to the diagnosis of this pathology, it is possible to confirm it during gestation, since the morphological features and the pathology associated to the Intrauterine growth can be identified through routine ultrasound (Luna-Domínguez, Iglesias-Leboreiro, Bernárdez-Zapata and Rendón-Macias, 2011).
At present there is no cure for Seckel syndrome, the treatment is usually geared towards genetic study and treatment of Medical complications through a multidisciplinary approach (Baquero Álvarez, Tobón Restrepo and Alzate Gómez, 2014).
Characteristics of Seckel syndrome
Seckel syndrome is a rare or rare disease. It is characterized by a pathological delay of the fetal growth during the gestation that Leads to the development of reduced body size, Microcephaly , Mental retardation Or a distinctive facial appearance known as the"bird's head or profile (Sanske et al., 1997; Bocchini, 2014).
Because of its low prevalence, Seckel syndrome is classified into rare diseases or disorders, ie those that affect a group Very reduced population of the general population, compared to other types of pathologies (Richter et al., 2015).
Although there are different prevalence scales, in the case of Europe, a disorder is part of rare diseases when it occurs with Less than one case per 2,000 people (Spanish Federation of Rare Diseases, 2016).
Generally, rare diseases are the product of genetic alterations or mutations, such as the Seckel syndrome (Richter et al., 2015). Thus, this pathology was initially described by Rudolf Virchow In the year 1892, based on his medical findings he gave the name of"head dwarfism Of bird".
However, it was not until 1960 that Helmont Seckel described the definitive clinical features of the syndrome (Baquero Álvarez, Tobón Restrepo and Alzate Gómez, 2014).
About us
As we have pointed out, the frequency of Seckel syndrome is scarce, so in 2010, approximately 100 Cases, of which more than 12 families had been identified (Baquero Álvarez, Tobón Restrepo and Alzate Gómez, 2014).
At the specific level, different epidemiological studies have estimated their frequency in less than 1 case per 10,000 children born alive. For another On the other hand, Seckel syndrome is a pathology that affects both genders equally, and has not been associated with any specific geographic region or Ethnic group (Luna-Domínguez, Iglesias-Leboreiro, Bernárdez-Zapata and Rendón-Macias, 2011).
Signs and symptoms
Clinical features of Seckel syndrome may vary to varying degrees, as they will fundamentally depend on their origin Specific etiology.
However, some of the most frequent signs and symptoms in this pathology include (Faivre and Comier-Daire, 2005; Organization for Rare Disorders, 2007):
Intrauterine growth retardation
The central medical finding of this pathology is the presence of an abnormally slow development of fetal growth during the gestation stage.
As we have pointed out above, Seckel syndrome is included in pathologies classified as dwarfimos, in which there is a delay Significant growth and bone age, fundamentally.
Normally, the slowed physical development usually continues after birth, during the neonatal and infantile stage, as a consequence, they may Develop secondary medical complications, such as those described below.
Microcephaly
Microcephaly is a type of neurological pathology in which the fundamental clinical finding is the presence of an abnormally cranial circumference Reduced, that is, the size of the affected person's head is smaller than expected for their gender and age group
Microcephaly may appear as a consequence of poor development of cranial structures or by the existence of a rate of growth abnormal.
However, in the case of Seckel syndrome, microcephaly is a product of intrauterine growth retardation, thus, the skull and brain Of the fetus They do not grow at a constant rate and in line with expectations.
Although the severity of the medical consequences of microcephaly is variable, it is usually accompanied by significant delays in the development, Learning deficits , physical disabilities , Convulsive episodes , among others.
In addition, the craniofacial structure of people affected by Seckel syndrome usually presents other characteristics, such as Craniosynostosis , is Say, early closure of the cranial sutures.
Short stature
Another significant feature of Seckel syndrome is the presence of a short stature, in some cases called dwarfism in the Medical literature.
Intrauterine growth retardation results in the presence of low birth weight, accompanied by delayed bone development or maturation.
Thus, during the postnatal phase, these characteristics lead to the development of abnormally short stature and limbs.
In addition, it can also lead to the development of other types of skeletal pathologies such as radia dislocation, Dysplasia Of hip Kyphoscoliosis , the Clinodactyly , or the Equinox foot .
Profile of Pájaro
Cranial and facial alterations give people with Seckel syndrome a distinctive configuration, characterized by different Morphological findings:
- Microcephaly : Reduced encephalic circumference, ie, abnormally small head.
- Facie reduced : Facial extension reduced or abnormally small, normally perceived at visual level as elongated and narrow.
- Frontal prominence : The forehead has a prominent or prominent structural configuration.
- Prominent nasal bridge : The nose usually presents an outstanding structural configuration in the form of a beak, in many cases, called nose Pico-horn.
- Micrognatia : Morphological structures of the mandible tend to appear smaller or smaller than normal, which may Cause important alterations in food.
- Large eyes : Compared to the rest of structures, the eyes can be observed larger than normal. In addition, in some cases It is possible to observe the development of altered processes such as exophthalmus or proptosis, that is, a profusion of eyeballs.
- Strabismus : In some cases, it is also possible to observe a deviation of one or both eyeballs, these can be turned towards the Outside or towards the nasal structure.
- Dysplastic Ears : The ears usually present an incomplete or deficient development, with an absence of lobes. In addition, Presenting a low craniofacial implantation.
- Cleft palate : The palate of the affected usually presents different alterations, like the arched ceiling or the presence of fissures or Clefts.
- Dental dysplasia : Dental pieces also tend to be poorly developed, with poor organization and overcrowding.
Intellectual Development Deficit
He Poor development Of the cranial and encephalic structure can cause a serious neurological and cognitive compromise in the people who suffer Seckel syndrome.
Thus, one of the most frequent findings is the presence of a deficit in intellectual development characterized by poor performance in the area Linguistic, memory, attentional and so on.
In addition, there are also different behavioral and motor alterations, such as stereotypies or episodes of aggressiveness.
Other features
In addition to the traits specified above, other types of medical complications may appear within the clinical course of Seckel syndrome:
- Genital dysplasia : In the case of affected males, the presence of Cryptorchidism Or poor Testicles into the scrotum. In the case of women, it is Clitoromegaly Or an abnormally large clitoris.
- Hirsutism : This term is often used to refer to an exaggerated or excessive presence of hair on the body surface.
- Hematologic deficiency : In many cases it is possible to identify a significant deficiency in one or several blood components (Red blood cells, white blood cells, platelets, etc.).
Causes
Seckel syndrome is a pathology with an origin Genetic Recessive, that is, it is necessary to have two copies of the gene Defective or altered in order for the disorder and its clinical characteristics to develop (Faivre and Comier-Daire, 2005).
In addition, for specific genetic abnormalities, Seckel's syndrome is widely heterogeneous, as they have now been identified Up to 3 types of alterations (Fitzgerald, O'Driscoll, Chong, Keating and Shannon, 2012), specifically located on chromosomes 3, 18 and 14 (Faivre and Comier-Daire, 2005).
In addition, three differential clinical forms of Seckel syndrome associated with genetic alterations have been identified (Faivre and Comier-Daire, 2005; Faivre and Comier-Daire, 2005):
- Seckel syndrome 1 : Associated with alterations in chromosome 3, specifically in the 3q22-P24 location and related to a mutation Specific in the Rad3 protein gene.
- Seckel 2 Syndrome : Associated with alterations in chromosome 18, specifically in the 18p11.31-q11 location, however, the mutation Has not yet been identified.
- Seckel 3 Syndrome : Associated with alterations in chromosome 14, specifically in the 14q21-q22 location, however, the mutation Has not yet been identified.
However, other studies indicate that Seckel syndrome may appear as a result of specific genetic mutations in the following Locations:
- Gen rbbp8 on chromosome 18.
- CNPJ gene on chromosome 13.
- Gen CEP152 on chromosome 15.
- Gen CEP63 on chromosome 3.
- Gen NIN on chromosome 14.
- Gen DNA2 on chromosome 10.
- Gene TRAIP on chromosome 3.
Diagnosis
The clinical and morphological features of Seckel syndrome, such as intrauterine growth retardation, microcephaly, or abnormalities Facial structures can be identified during gestation.
Thus, fetal ultrasound is one of the most effective methods, which allows visual and metric detection of bone structural abnormalities and Alteration of the rhythms of physical development (National Organization for Rare Disorders, 2007).
However, such pathologies can not be confirmed clinically until the medical picture is completely developed, Early childhood (National Organization for Rare Disorders, 2007).
In addition, another important point is the genetic study since it allows to study the familiar history and the hereditary patterns.
Treatment
At present, no type of medical approach has been identified to cure or slow the progression of the Seckel syndrome. However, they may Different treatments for symptomatic improvement should be used (Baquero Álvarez, Tobón Restrepo and Alzate Gómez, 2014).
Thus, the treatment is usually geared towards the genetic study and treatment of medical complications through an approach Multidisciplinary (Baquero Álvarez, Tobón Restrepo and Alzate Gómez, 2014).
In addition, the control of hematological deficiencies and therefore the treatment of other secondary medical complications such as anemia , Pancytopenia or leukemia among others.
References
- Baquero Álvarez, J., Tobón Restrepo, J., & Alzate Gómez, D. (2014). Two cases with Seckel Syndrome in a Colombian family. Rev Mex Pedr, 69-73.
- Bocchini, C. (2014). SECKEL SYNDROME. Obtained from Johns Hopkins University.
- Comier-Daire, V., & Faivre-Olivier. (2005). Seckel Syndrome. Obtained from Orphanet.
- Fitzgerald, B., O'Driscoll, M., Chong, K., Keating, S., & Shannon, P. (2012). Neuropathology of fetal stage Seckel syndrome: A case report providing Morphological correlate for the emerging molecular mechanisms. Brain & Development, 238-243.
- Luna-Domínguez, C., José Iglesias-Leboreiro, J., Bernárdez-Zapata, I., & Rendón-Macías, M. (s.f.). A case with Seckel-Like syndrome. Rev Mex Pedr.
- NORD. (2007). Seckel Syndrome. Retrieved from the National Organization for Rare Disorders.