Bloch-Sulzberger syndrome is a genetic form of skin pigmentation disorder. Pathology is often combined with malformations of the eyes, nails, hair and teeth. According to ICD-10, the Bloch-Sulzberger syndrome has a code of P 83, that is, other changes in the external integument that are specific to the newborn and fetus. They are considered in dermatovenerology - a medical field that studies sexually transmitted and skin pathologies, their treatment and prevention.
Description
Bloch-Sulzberger Syndrome (neurodermal melanoblastosis, a familial form of pigment incontinence) is a genetic disease that is characterized by a defect in melanin metabolism in the skin and some associated malformations. This disease was first described by a dermatologist from Switzerland B. Bloch in 1926, then M. Sulzberger, an American pediatrician, studied this pathology in more detail in 1929, and, independently of other researchers, G. Siemens, a German doctor. That's why there is another name in the literature - Bloch-Siemens syndrome.
Who is more often detected?
Diagnosed with Bloch-Sulzberger syndrome in newborns, many times more often in girls. At the same time, the sexual distribution is approximately 6: 210, since the presence of such a mutation in male embryos is almost always fatal and causes spontaneous termination of pregnancy. In boys, the development of the disease can be triggered by genetic mosaicism, the presence of concomitant Klinefelter syndrome and infrequent “soft” point mutations. Moreover, for Bloch-Sulzberger syndrome, the total incidence is about 1: 75,000 newborns. Clinical supervision at the children's doctor and related doctors is recommended.
Causes of pathology
With Bloch-Sulzberger syndrome, the IKBKG gene located on the X chromosome is damaged. The result of its expression is a complex multifunctional protein, that is, the regulatory subunit of the NEMO-inhibitory kinase, which takes part in the NF-kappa-B signaling system, a significant transcription factor. This factor and the signaling pathway corresponding to it regulates many different processes in the human body - it takes part in adaptive processes during the immune response, stress, cell adhesion processes, some types of inflammatory reactions, and also stops apoptosis processes. The most common cause of Bloch-Sulzberger syndrome is large deletions and translocations of the IKBKG gene, as a result, protein isolation and expression of this gene cease completely.
Since women have two X chromosomes, in the presence of a normal second allele of the IKBKG gene, such a mutation does not threaten life, but it provokes the development of this pathology. There is a fact that in the somatic cells of a woman’s body, only one X chromosome is always active, while the second chromosome is condensed into sex chromatin. Strong variability of the symptomatic severity of the disease is caused by cell distribution, where the chromosome with the mutant form of the IKBKG gene is active. As a result, the regulatory subunit of the NEMO-inhibitory kinase is not formed in the above cells, which causes typical malformations that form the clinical picture of the disease.
Men, unlike women, normally have only one X chromosome, and therefore, when a nonsense mutation in the IKBKG gene does not occur, the release of an important protein in all cells of the body. In boys, the development of abnormalities similar to Bloch-Sulzberger syndrome may occur in the presence of the concomitant XXY karyotype (Klinefelter syndrome) or genetic mosaicism, in which some of the cells in the body have a violation of the IKBKG gene. But most often, boys with similar defects do not develop the syndrome that we describe, but other genetic diseases - skeletal malformations, immunodeficiencies and ectoderm dysplasias.
Symptoms of the disease
Among the most common and pronounced symptoms of the Bloch-Sulzberger syndrome is dermatosis, which is detected at birth or occurs less frequently during the first days of a baby's life. In the development of changes in the skin integument with such a disease, characteristic staging is noted, which is also a significant indicator of diagnosis. Localization of these changes is observed on the lateral surfaces of the arms and legs, neck, trunk, along the projections of the main nerve trunks or Charcot lines.
Dystrophy of nails and alopecia
In addition to the manifestations on the skin, Bloch-Sulzberger syndrome can cause the development of nail dystrophy, focal alopecia. In almost 80% of patients, anomalies of the dentition are observed - the absence of teeth and their curvature. In half the cases of pathology, visual disturbances are determined - strabismus, cataracts, atrophy of the eye nerve and some other disorders. Mental development often does not suffer, but there may be a certain delay. Oligophrenia is very rare. All pathogenic manifestations have a tendency to weaken after the end of adolescence.
Stages
The disease is characterized by a colorful picture of the components of the rash, as a result of which four successive stages of development are noted.
- Stage I - erythematous vesicular. Blisters, spots, blisters, vesicles, pustules arise, which are linearly in the form of strips along the nerve trunks. Elements of the rash are most often localized in the area of the lateral surfaces of the body and on the limbs.
- Stage II - hypertrophic. Hyperkeratotic, warty, lenticular and lichenoid plaques and papules appear on an infiltrated base, which are located both linearly, symmetrically, and randomly.
- Stage III - pigmented. It is characterized by the presence of peeling brown-yellow spots, which are similar to traces of the ebb of waves or splashes of dirt.
- Stage IV has mild atrophy and depigmentation areas. Staged rash elements are not always maintained.
Diagnostics
To diagnose pigment incontinence and Bloch-Sulzberger syndrome, a large number of diagnostic techniques and methods are used - the study of genetic history, dermatological examination, histological analysis of the affected areas of the skin integument, molecular genetic studies.
During the examination, various (depending on the stage of the disease and age of the patients) skin changes of the hyperkeratic, vesicular or erythematous type are determined, focal hypo- or hyperpigmentation of the epidermis can be established in older patients.
In addition to these signs, there may be alopecia, dystrophy of the nails and abnormalities in the structure of teeth in people with Bloch-Sulzberger syndrome. Photos do not reflect all the symptoms.
A genetic history can establish a dominant, familial and chromosome X-linked mode of inheritance of the disease.
The mother of the patient in some cases has a history of several situations of spontaneous abortion, which is associated with death inside the womb of the male fetus. The results of a histological analysis of skin tissues with Bloch-Sulzberger syndrome are determined by the stage of pathology - at the first stage, spongiosis is diagnosed, as well as the development of epidermal blisters filled with fibrin masses and eosinophils. At the second stage of the disease, acanthosis, symptoms of intraepithelial keratinization and hyperkeratosis are detected, edema with eosinophilic and neutrophilic infiltration is noted in the dermis. The third stage of the syndrome is characterized by the disappearance of inflammatory changes in the dermis (infiltration, edema), but the appearance of a significant accumulation of pigment in the upper skin layers. The fourth stage of Bloch-Sulzberger syndrome in newborns (pictured) is characterized by the loss of pigment, the formation of fibrous tissue and the disappearance of a certain part of the skin appendages.
Molecular genetic diagnosis
Molecular genetic diagnosis of Bloch-Sulzberger syndrome is performed by a genetic doctor and can be carried out in several main ways. Direct automatic sequencing of the sequence of the IKBKG gene makes it possible to detect almost any of its structural changes. Deletions and translocations of significant regions of the gene, often appearing as the cause of the Bloch-Sulzberger syndrome, are detected by FISH analysis. This disease can also be confirmed by analysis of the inactivation of X chromosomes in affected tissue cells.
How is the follow-up for Bloch-Sulzberger syndrome?
Methods for treating the disease
Currently, there is no specific therapy for the syndrome; skin lesions in the inflammatory stage of the disease are treated with antiseptic solutions and agents to prevent possible complications of the infection. In addition, local administration of glucocorticoid steroids to reduce inflammation is desirable, but such treatment should be done carefully, given the high permeability of the skin in young children. Other symptoms (developmental disorders of the eyes, teeth) are treated when indicated.
What is the prognosis for Bloch-Sulzberger syndrome in dermatovenereology?
Prevention and prognosis for this pathology
Most often, the prognosis for the syndrome is favorable, since from the beginning of the process of puberty, pathogenic manifestations significantly weaken. The prognosis can worsen changes in the nervous system, internal organs, eyes, which are rarely observed with such a pathology. Also, in some cases, primary immunodeficiency may appear, significantly worsening the prospects of the disease. Prevention of pathology consists in medical and genetic counseling of parents and prenatal diagnosis with burdened heredity in a woman planning a pregnancy.