This is a rare congenital pathology, characterized by the fact that the child is born with immediately noticeable multiple deviations from the norm. Subsequently, the infant also shows signs of mental retardation.
The first to describe the syndrome as an independent disease was the German physician V. Brahman in the early twentieth century. A little later, a pediatrician from the Netherlands, Cornelia de Lange (de Lange), led two small patients suffering from the disease and described it in detail. This pathology can also be called the Brahman-de Lange syndrome or degenerative nanism (dwarfism) of the "Amsterdam" type, because Three children with this diagnosis lived in the capital of the Netherlands.
Epidemiology
Epidemiology of the Cornelia de Lange syndrome: it is rare, newborns with such pathology appear in approximately one case of 10 to 30 thousand genera, other sources call even lower indicators - one case of 100 thousand. In total, more than 400 cases of this disease are known in different countries, boys and girls are approximately equally divided among them.
Causes of the cornelia de Lange syndrome
The etiology and pathogenesis of this syndrome has not yet been established and are under study. There are assumptions that the disease is hereditary and may be due to various genetic anomalies, although the gene responsible for intrauterine development disorders and the type of its transmission has not yet been determined (a hypothesis about mutations in the BIPBL gene (HSA 5p13.1) encoding delangin is put forward).
Mutations in the genes that encode two other proteins involved in the cohesion of sister chromatids, SMC1A and SMC3, were reported in 5% and 1% of patients with Cornelia de Lange syndrome, respectively.
Analysis of the samples of this disease suggests that the inheritance of a mutant gene in this case is not characterized by a primitive transfer. Probably, over time, an improved cytogenetic study will be able to identify pathology at the chromosomal level.
Most of the studied episodes of the Cornelia de Lange syndrome are single, and there were usually no changes in the chromosome set of patients, although anomalies were occasionally detected - more often there was fragmentary trisomy over the long arm of chromosome 3 and chromosome 1, and chromosome 9 had the shape of a ring.
There are also known cases of disease of members of one family, in the analysis of which, an assumption is made about the autosomal recessive way of transferring the gene that provokes this pathology.
Nevertheless, in the manifestations of the syndrome, members of one family do not have complete or partial underdevelopment of the limbs, as in single cases. Based on this, a hypothesis is advanced about the differences in the causes of family and single cases of Cornelia de Lange syndrome.
The influence of the father's age on the incidence of a child with this disease is more than controversial, so it is still unclear whether this syndrome can trigger single autosomal dominant transformations of the genotype.
Risk factors
Risk factors - the presence of a family history of this syndrome, tk. In this case (if the assumption of the recessive method of gene transfer is true), the possibility of the appearance of the next child with pathology is 25%. The degree of probability of repetition of the situation in single episodes, in the absence of chromosomal mutations in parents, is theoretically 2%.
It is assumed that the transformation of chromosomes arise due to severe infections and intoxications carried by the expectant mother during the first three months of pregnancy, side effects of chemotherapeutic drugs and some physiotherapeutic procedures. Genetic mutations can be promoted by endocrine diseases of the mother, radiation, a solid age of the father of the child or maternal age of more than 35 years, and also when the mother and father are blood relatives.
Symptoms of the cornelia de Lange syndrome
It is characterized by numerous developmental defects, which are usually noticeable, although sometimes they are detected only through diagnostic procedures.
The main symptoms of Cornelia de Lange syndrome:
- "Bizarre face" - thick hair for the newborn scalp, connected eyebrows and long curled cilia, deformation of the ears and a small nose with open nostrils from the front, the gap from the upper lip to the tip of the nose is abnormally large, a thin red border of the upper lip, the corners of the lips are lowered;
- microcephaly of the brain;
- brachycephaly - a decrease in the height of the skull with a simultaneous increase in its horizontal size;
- pathology of the oral cavity and nasopharynx - atresia of the khohans, arched sky with a cleft, failures in the process of eruption of milk teeth.
- dysfunction of vision - strabismus, lens-shaped abnormalities, cornea, eyes, myopia, atrophy of the optic nerve;
- shortened extremities, their ectrodactyly, oligodactilia and other abnormalities of the limbs;
- leather of marble color;
- abnormalities of nipples and genitals;
- hypervelocity of the body;
- episodic convulsive alertness, hypotension, hypertension of muscles;
- dwarfism;
- mental retardation of varying degrees - from minor abnormalities (rarely) to oligophrenia and imbecility in most cases.
The first signs of the disease are visually apparent in newborns. In addition to external features, attracts attention to the small weight of the child at birth - it is 2/3 the weight of a healthy child, born on a similar period of pregnancy. Newborns have problems with feeding and breathing. From an early age, suffer frequent infectious-inflammatory diseases of the respiratory tract due to the specific structure of the nasopharynx.
When autopsies of deceased patients, various defects of the brain are detected (underdevelopment of the inferior frontal gyrus, ventricular expansion, dysplasia and gipoplasia of convolutions), histology often shows a pronounced transverse pattern of neurons in the outer granular layer of the cortex of the cerebral hemispheres and disorder of the topography of the neurons of the cerebellum.
More than half of all cases of Amsterdam Nanism are accompanied by defects in the structure of the heart (aorto-pulmonary window, an unprotected septum separating both the atria and the ventricles, often in combination with vascular disorders, the tetralogy of Fallot), defects in the structure of the gastrointestinal tract (mainly impaired turning intestine), urogenital system (cystic kidney formation, single and multiple, sometimes - horseshoe kidney and hydronephrosis of its changes, cryptorchidism, bicorne uterus).
This disease, characterized by a number of developmental defects, is inherently not yet discovered by the genetic anomaly that begins at the time of embryo formation. The process triggered by the pathogenic factor continues and is further aggravated after the birth of the child. The stages of the disease go hand in hand with biochemical pathologies in the brain neurons throughout all stages of the maturation of the organism. Such lesions are accompanied by mental retardation, and the existing multiple behavioral and external deviations in the patient does not yet indicate the end of the process in the prenatal period.
Forms
Modern psychiatry classifies the following types of this syndrome:
- Classic (first), when all the symptoms are clearly manifested: specific appearance, multiple developmental defects, marked mental retardation.
- The frayed appearance (the second), in which the same defects of the face and trunk occur, but there are no incompatible anomalies of internal organs, motor, mentality and intellect disorders are poorly expressed.
According to the observations of parents, children with such a disease at any age do not ask for toilet, are prone to irritability, constantly commit meaningless, not typical for healthy children actions: tear or eat paper, break anything that comes across their eyes, move around in circles. It brings peace to them.
Complications and consequences
The consequences and complications of the presence of de Lange syndrome are unfavorable, people are very dependent on others, live independently, without constant help they are not able, in classical cases, death from any pathology of internal organs development is possible in infancy.
Diagnostics of the cornelia de Lange syndrome
At the present stage of the development of diagnosis it is impossible to detect the presence of this pathology in the embryo. The risk factor for the syndrome is the absence in the serum of a pregnant woman of protein-A plasma (RAPP-A), which is normally produced during pregnancy in large quantities. However, to accurately diagnose the presence of the disease in the embryo only by the results of this test is impossible, because in 5% of cases of normal pregnancies, a false positive result is observed, and chromosomal abnormalities in the fetus are detected only in 2-3% of cases of a decrease in the level of this protein.
Amsterdam's dwarfism is determined in newborns by characteristic external features.
Multiple defects and anomalies that are incompatible with life must be diagnosed in time, so that the surgical intervention necessary to preserve life can be carried out.
Instrumental diagnostics is carried out with the help of magnetic resonance imaging, ultrasound and radiographic examination, rhinoscopy and other modern diagnostic methods as needed.
The patient is made as a standard clinical analysis, and cytogenetic.
Diagnosis is carried out in two stages: a clinical examination of the state of the newborn, corresponding to modern techniques, and differential diagnosis of a specific genetic pathology. It is based on the differentiation of such lesions with the most typical symptomatic manifestations of the syndrome.
Diagnosis of the de Lange syndrome is sometimes controversial, since children with mental retardation and a small number of defects - signs of the disease - come across. Since there is no indisputable biological method of confirming the diagnosis, it is impossible to determine precisely whether these episodes refer to this syndrome.
Treatment of the cornelia de Lange syndrome
Specific methods of treatment of this condition are absent. Infants in cases of necessity make operations to eliminate developmental defects that are not compatible with life.
In the course of a later life, therapeutic procedures are prescribed - physiotherapeutic, psychotherapeutic, massage, wearing glasses and the like for symptomatology. Medicamentous treatment - nootropics, anabolics, vitamins, anticonvulsants and sedatives.
Prevention
Prevention of the syndrome, the factors of occurrence of which are not precisely established, it is difficult to deal with.
However, given the known sources of gene mutations, it can be recommended as preventive measures:
- prevention of conception of children from mother and father - blood relatives;
- carefully monitored in case of late maternity and paternity;
- pregnant women, avoid infection with viral infections, especially in the first trimester, and in case of infection, use medicinal therapy only as directed by the doctor.
Women and men with a family history of Cornelia de Lange syndrome must visit a medical genetic consultation. During pregnancy, women need to be screened for protein-A plasma.
Forecast
The life expectancy measured to people with this disease depends on many factors, the most important of which can be called - the severity of the vices of vital organs, their early diagnosis and the quality of surgical interventions to eliminate them.
With developmental anomalies incompatible with life, a child dies in the first week of life. In case of their insignificance or timely surgical removal, a patient with Cornelia de Lange syndrome can live long enough. Predicting is complicated by the lack of resistance of the organism of patients with this syndrome to ordinary, non-dangerous infections for common people, for example, viral infections, which also cause the early death of such patients.
The average life expectancy of about 12-13 years, according to some sources, patients with an erased form of the disease or successfully performed operations to eliminate developmental defects sometimes survived to the fifth or sixth decade.