The Cornelia de Lange syndrome is a pathology of genetic origin that is characterized by the presence of a significant cognitive delay accompanied by various malformative physical traits.
At the clinical level, three differential clinical courses are observed: severe, moderate and mild. The signs and symptoms are usually constituted by an atypical facial configuration, musculoskeletal malformations and delayed cognitive and psychomotor development. In addition, other types of abnormalities related to cardiac, pulmonary, and / or digestive malformations may be distinguished..
Regarding the origin of Cornelia de Lange syndrome, its etiology has been related to the presence of specific mutations in the genes SMC3, SMC1A, NIPBL, among others. The diagnosis is fundamentally clinical, made on the basis of physical and cognitive characteristics. However, it is usually accompanied by a confirmatory genetic test.
Treatment is geared toward the detection and treatment of medical complications. Medical, speech therapy, neuropsychological intervention and special education are essential.
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This syndrome was initially described by Dr. Cornelia de Lange in 1933. Her research was based on the study of two patients aged 6 and 17 months. His clinical picture was characterized by a severe delay in physical growth and intellectual development associated with various malformative traits..
Given the similarity of both cases, the first clinical report on this pathology assumed the existence of a common and public etiological cause.
Previously, Brachmann (1916) had managed to publish some autopsy data of a child-age patient with some characteristics compatible with Cornelia de Lange syndrome..
At present, the clinical picture of this syndrome has been classified into three differential phenotypes: severe, moderate and mild..
Cornelia de Lange syndrome is a rare genetic disorder of a congenital nature, that is, its clinical characteristics are evident from birth. It is defined as being a multisystemic disease with symptoms associated with delayed physical and cognitive development, cranio-facial malformations or musculoskeletal malformations..
Although the clinical course and severity of this syndrome can vary considerably among those affected, it is a disease with a high mortality rate.
People with Cornelia de Lange syndrome are characterized by an atypical or characteristic facial configuration and a delay in pre and postnatal growth / development..
The most common is that learning problems appear, delayed language acquisition or gait and behavioral abnormalities.
Cornelia de Lange syndrome is a rare disease in the general population, it is usually classified within rare diseases. Epidemiological data are not exactly known. Its incidence has been estimated at one case per 10,000-30,000 births..
To date, we can find more than 400 different cases of Cornelia de Lange syndrome described in the medical and experimental literature..
It is a pathology that can affect both sexes in equal numbers. Some authors such as Gutiérrez Fernández and Pacheco Cumani (2016) suggest a slight predominance towards women, with a ratio of 1.3 / 1.
Regarding the rest of sociodemographic factors, current research has not identified a differential prevalence associated with specific countries or ethnic and / or racial groups..
A good part of the diagnosed cases are sporadic, although several affected families have been identified with a clear pattern of dominant inheritance.
The signs and symptoms of Cornelia de Lange syndrome are characterized by their broad pattern of involvement.
This disease is defined by the presence of characteristic facial features, musculoskeletal malformations in the upper and lower limbs, generalized delay in pre and postnatal growth, along with the development of other physical abnormalities..
Next, we will describe some of the most frequent clinical features in Cornelia de Lange syndrome:
In more than 90% of those affected by Cornelia Lange syndrome, it is possible to identify a delay in physical development or global hypogrowth. Growth is usually affected both prenatally and postnatally.
The most common characteristics in newborns are:
These conditions usually last into adulthood. In it, a growth located below that expected for the sex and biological age of the affected person can be distinguished..
Along with these types of alterations, some abnormalities related to feeding can be identified. Difficulty swallowing or chewing food is common during the early stages of life.
The combination of cranial and facial alterations results in the development of a characteristic facial phenotype in people suffering from Cornelia de Lange syndrome..
Some of the more common abnormalities include:
Delay in cognitive and psychomotor development constitutes one of the central clinical findings in Cornelia Lange syndrome. A slow acquisition of skills related to motor or mental activity is usually identified.
The most affected milestones are the acquisition of sitting, the affective smile, the babbling, the independent movement, the emission of the first words, the comprehension and orders, the feeding, ambulation or independent toilet.
In many of those affected, an average IQ associated with mild or moderate intellectual disability can be identified.
The behavior of those affected by Cornelia de Lange syndrome usually presents some distinctive features:
Cornelia de Lange syndrome is also associated with the development of various medical complications.
The most frequent causes of death or worsening of the medical status of those affected are related to:
The variability of the signs and symptoms of Cornelia de Lange syndrome has made it possible to classify its clinical course:
It is usually the most serious. The alterations and anomalies are characterized by the presence of physical undergrowth, musculoskeletal malformations, abnormal facial features, limitation of joint mobility, cognitive delay and other medical complications (auditory, ocular, digestive, reno-urological, cardiac and genital)..
In this subtype, the physical alterations are usually not very evident, especially in the extremities. Those affected do not usually have serious intellectual deficits. The most common is that the diagnosis is made beyond the neonatal stage.
Its clinical course is fundamentally characterized by clinical variability. Facial characteristics are present in most cases, but the expression of the rest of the anomalies is variable..
The origin of Cornelia Lange syndrome is associated with the presence of genetic abnormalities. In the cases examined, it has been possible to identify specific mutations in 5 different genes: NIPBL, SMC1A, HDAC8, RAD21 and SMC3.
The most common alteration is related to the NIPBL gene, identified in more than half of those affected. The rest of genetic anomalies are less frequent.
All these genes have a prominent role in the production of proteins related to the cohesin complex, responsible for the regulation of chromosomal structure and organization, stabilization of genetic information in cells and DNA repair..
In addition, they also fulfill several fundamental functions in the prenatal development of the extremities, the face and other regions and body systems..
The diagnosis of Cornelia de Lange syndrome is clinical. Currently there is no laboratory test that definitively indicates its presence. In the medical area, the most common is to use the diagnostic criteria proposed by Kline et al..
These refer to the identification of craniofacial anomalies, in growth and development, in the extremities, neurosensory and skin alterations, behavioral disorders, etc..
In addition, it is important to carry out a molecular genetic analysis to identify the presence of mutations associated with Cornelia de Lange syndrome..
Although there is no cure for Cornelia de Lange syndrome, its therapeutic approach involves the design of a continuous medical follow-up together with the treatment of complications..
The authors Gil, Ribate and Ramos (2010) point out some of the most used approaches.
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