What is phacomatosis?

Fakomatozy, or neyrokozhnye syndromes - is a whole group of diseases characterized by simultaneous damage to the skin, nervous system and internal organs that arise from similar embryonic violations. That is, the origins of phakomatosis are genetic. The name itself does not say anything to the man in the street. It may seem that these are some outlandish and completely uncommon illnesses. But here, for example, about albinism, perhaps, everyone heard. And this is a real phakomatosis. A total of more than 30 diseases are included in the group of known neurocausal syndromes. Each of them has its own clinical features. From this article you can learn more about the most common phakomatoses.

Why develop phakomatosis?

At the heart of most phakomatoses is a genetically conditioned defect of embryonic development (a mutation in one of the human genes). For each variety of neurocess syndrome, the mutation is localized in a particular gene.

The nervous system and skin are formed from the same layer of germ cells. Some internal organs are partially formed from the same layer. Therefore, the only genetic defect is manifested by the simultaneous defeat of seemingly completely different structures. However, the time of occurrence of such lesions is different: skin changes, for example, can be seen already when birth, whereas the symptoms of nervous system damage can appear only in adolescent or even adults age. Common for all phakomatoses are tumor growths in the form of fibroids, angiomas, telangiectasias, as well as disorders of skin pigmentation. At the same time, each species has its own specific symptoms.

What diseases are referred to as phacomatoses?

The most common phakomatoses include diseases such as:

• Type I neurofibromatosis (Recklinghausen's disease);
• neurofibromatosis type II (bilateral auditory neurinoma);
• tuberous sclerosis (Burneville-Pringle disease);
• Sturgeon-Weber syndrome (encephalotrigeminal angiomatosis);
• syndrome Klippel-Trenone-Weber (hypertrophic hemangiectasia);
• ataxia-telangiectasia (Louis-Bar syndrome);
• Hippel-Lindau disease (retinocerebrovascular angiomatosis);
• Osler-Randu-Weber disease (hereditary hemorrhagic telangiectasia);
• hypomelanos ito;
• pigment incontinence (Bloch-Sulzberger syndrome);
• albinism.

Clinical signs of phacomatosis

Type I neurofibromatosis (Recklinghausen's disease)

In patients with type 1 neurofibromatosis, a large number of neurofibromes appear on the body.

This is a fairly common disease: according to various sources, its frequency ranges from 1 case per 2500 population to 1 at 7800.

The genetic defect is located on the 17th chromosome. The disease manifests itself in the first few years of life. Type I neurofibromatosis is characterized by clinical symptoms from various organs and systems.

Disturbances of skin and eye pigmentation:

• in the form of spots of coffee and milk. The number and size of the spots vary depending on the age: before the adolescent period for such their diagnosis should be at least 5 diameters greater than 5 mm, after puberty - 6 spots with a diameter 15 mm;
• freckled rashes of 1-3 mm in the armpits, inguinal areas, popliteal fossa that may first appear in response to the effect of a provoking factor (intertrigo, friction clothing, minor injuries);
• Nodules Lisha - pigmented areas of the iris (see them only when viewed in a slit lamp). The color of the nodules differs from the color of the iris. They do not show themselves, they do not cause anxiety and do not affect vision, but they are a very specific symptom for this phakomatosis.

Disorders of the nervous system:

• Neurofibroma: benign neoplasm proliferation from the nerves. They can be cutaneous, subcutaneous and plexiform. Are located in any part of the body.Skinneurofibromas look like nodal formations from a few millimeters to a meter in diameter, they are located on a stem or on a wide base, purple-red. They are soft to the touch and not soldered with the underlying tissues.Subcutaneousneurofibromas are denser and still, ranging in size from a few millimeters to 3-4 centimeters, painful when palpating.Plexiformcombine the characteristics of the previous two types of neurofibre. All of them have a tendency to increase and increase in numbers, in connection with which they squeeze the surrounding organs and tissues, which causes the corresponding symptomatology (for example, compression of the larynx causes disturbances in breathing and tone vote);
• Tumors of the visual pathways (gliomas): located in any area of ​​nerve wires carrying information about the image. In the beginning they are asymptomatic, but as they grow, they cause a decrease in vision, the lowering of the eyelid and protrusion of the eyeball;
• disorders of mental development, epileptic seizures, fainting, migraine headaches.

Lesions of other organs and systems:

• phacocosteal disorders: underdevelopment of the sphenoid bone, scoliosis, spinal anomalies in combination with meningocele (protrusion of the meninges under the skin), large skull (macrocephaly), pseudoarthrosis, crooked leg, cystic changes in bones;
• anomalies of the vessels, leading to a narrowing of their lumen and a violation of blood circulation.

Neurofibromatosis type II (bilateral auditory neurinoma)

A specific symptom of type 2 neurofibromatosis is a bilateral tumor of the pre-cochlear nerve and the resulting hearing loss.

This phakomatosis is less common. The frequency is 1 case per 30 000-40 000 population. The reason is a mutation in the region of the 22nd chromosome.

The main features are:

• tumor formation of the cranial nerves: Especially specific is the bilateral Schwannoma VIII pair, which leads to a decrease or loss of hearing. This type of tumor has an uneven surface and contains hair, which is specific for Type II neurofibromatosis. Also, glioma of the optic nerve is often detected;
• tumors from the shells of nerve conductors of different locations (brain, limbs, internal organs, nasolabial folds, palms): meningiomas, neurofibromas, gliomas, schwannomas;
• posterior subcapsular cataracts: they cause a sharp decrease in vision. May be the first manifestation of the disease.

For type II neurofibromatosis, the following characteristic is characteristic: a prolonged asymptomatic course. That is, tumor formations, despite their presence, do not make themselves felt for years. The first clinical signs can appear only in adolescence (or even after 30 years), with the tumors may already be quite impressive sizes. Skin symptoms in the form of spots of coffee color with milk, freckles, bending of bones, Lish's nodules are not characteristic (they can be in a small percentage of patients). Usually only an accidental MRI of the brain (carried out for another reason) reveals changes in the preclinical stage.

Tuberous sclerosis

On average, there is a frequency of 1 case per , 00 population. Genetic defects can be located in the 9th, 11th, 16th chromosome regions. It manifests itself by such signs:

• changes in the skin and its appendages:
• hypopigmented (light) spots from 3-4 to 100. They appear in the first three years of life;
• discoloration of strands of hair, eyebrows, eyelashes;
• adenomas of the sebaceous glands on the face (angiofibroma of the face). These are small nodules pinkish-reddish color, located in nasolabial folds, on cheeks in the form of "butterfly wings
• Fibrous seals of small size, creating a roughness effect when feeling. The accumulation of such areas, slightly protruding above the surface of the skin resembling a pig's hide, is called "shagreen skin
• okolonogtevymi fibromas: dull multiple nodules on the fingers, under the fingernails (more often on the legs);
• defeat of the nervous system in the form of mental retardation of varying severity and epileptic seizures;
• pathology of internal organs:
• angiomyolipomas and renal cysts;
• benign tumors of the heart and lungs;
• polyps of the intestine;
• eye symptoms (tumors of the eyeball in the form of mulberries, cataracts, atrophy of the optic nerve, etc.).

Quite heavy lesions of internal organs, frequent epileptic seizures with this phacomatosis can cause deaths in the age of up to 30 years.

Sturgeon-Weber Syndrome (encephalotrigeminal angiomatosis)

There is a frequency of 1 case per 50 000-100 000 population. The exact genetic defect is not established.

The most demonstrative symptoms are:

• congenital pigmentary nevus (cutaneous hemangioma) on a large face ("port" or "flame" nevus): a spot of bright red or cherry color that captures almost half of the face. Usually one-sided, but can be located on both sides. The dimensions of the nevus in the proportions of the face do not change during life (it grows with the child);
• epileptic attacks of focal type followed by generalization. After seizures, muscle weakness in one half of the body (paresis) persists for some time;
• dementia;
• increased intraocular pressure (glaucoma) from the pigment nevus. Can be congenital or develops by the 2nd year;
• calcification in the brain.

There are so-called rudimentary forms of this disease, characterized by the appearance of only some of the symptoms described above, which makes it difficult to diagnose.

If encephalotrigeminal angiomatosis is combined with the defeat of internal organs in the form of angiomas, this version of phakomatosis is isolated in a separate form - the Klippel-Trenone-Weber syndrome.

Ataxia-telangiectasia

This phakomatosis occurs with a frequency of 1 case per 40 000-100 000 population. The mutation occurs in chromosome 11.

The disease manifests itself in childhood as a multitude of symptoms. The most typical signs are:

• cerebellar ataxia: instability in walking and standing, swinging gait, impaired coordination of movements when trying to take an object, trembling of fingers, violation of speech in the form of dividing words into syllables with emphasis on each of them, spontaneous oscillatory movements of the eye apples. Over time, these manifestations are accompanied by an increase in muscle tone, which prevents the movement, impoverishment of mimicry, involuntary movements in the hands, a peculiar installation of the fingers, a bent posture;
• telangiectasia (vascular sprouts): widening of the venous capillaries. They appear at the age of 3-6, first on the conjunctiva of the eyes, and then on the open surfaces of the skin (face, ears, elbows, popliteal fossa), are not accompanied by pain;
• frequent infectious diseases of the respiratory system, intestinal infections. This is due to the underdevelopment of the thymus (immune organ) and, as a consequence, a defect in the immune response;
• propensity to malignant neoplasms, such as leukemia, lymphosarcoma (which is also associated with a defect in the immune system);
• lag in growth, early gray;
• underdevelopment of the tonsils (or even their absence);
• condensation and dryness of the skin, seborrheic dermatitis.

The disease is steadily progressing. Immune deficiency causes chronic purulent diseases of the bronchopulmonary system. Children die from affiliated infections or malignant tumors. In rare cases, with maintenance therapy, such patients survive to 30-40 years.

Hippel-Lindau disease

Hemangioma of the retina is the cause of eye pain and loss of vision in persons with Hippel-Lindau disease.

Fakomatoz is associated with a genetic mutation in the 3rd chromosome. The main manifestation of the disease is multiple angiomas that arise in the most diverse parts of the body.

The most typical symptoms are:

• hemangiomas of the retina, which cause pain in the eye, loss of vision, and subsequent hemorrhages, retinal detachment and loss of vision;
• angiomas of the cerebellum (occur in at least 60% of patients): manifest themselves as cerebellar ataxia with dizziness, instability and unsteadiness in walking, awkwardness and awkward movements. As the tumor grows, there are signs of increased intracranial pressure;
• hemangiomas of the spinal cord, which debut with impaired sensation, and then with muscle weakness;
• kidney damage (cysts, adenomas, hemangiomas, carcinomas);
• vascular neoplasms of the liver, pancreas, testicles;
• pheochromocytoma (adrenal tumor).

The disease is characterized by steady progression, and tumor growths tend to recur even after removal.

Osler-Randu-Weber disease

This phakomatosis can be associated with a mutation in the 5, 9 or 12 chromosome region. It is rare - 1-2 cases per 100 000 population.

The essence of the disease consists in the defeat of blood vessels with thinning of their walls and increased vulnerability. As a result of these changes, bleeding occurs: nasal, gastric, renal, pulmonary. Small hemorrhages to the brain also occur.

On the skin, mucous membranes and internal organs appear telangiectasias.

Most often, the disease first manifests itself as nosebleeds already in childhood. After this, the first telangiectasies begin to appear, the number of which increases with age.

The amount of blood loss is very individual: from a few drops to 500 ml and even more. Constant hemorrhage leads to iron deficiency anemia.

The defeat of the nervous system is very diverse, because the symptoms depend on the place of the outpouring of the blood in the brain or spinal cord. The most frequent complaints are headaches, dizziness, and muscle weakness. The longer a disease exists, the greater its manifestation.

Massive bleeding carries a threat to the life of the patient and requires the transfusion of blood and its components.

Hito's Hypomelanoz

This phakomatosis in most cases is a sporadic (accidental) disease. Single cases with inheritance transfer are described. B, times more common in women.

Main clinical symptoms:

• hypopigmentation of skin areas in the form of curls, streaks, zigzags, marbled divorces (revealed at birth or in the first six months of life). After the puberty period, the spots become less pronounced, and in some places disappear completely;
• Mongoloid blue spots on the skin, spots of coffee color with milk;
• epileptic seizures that are not amenable to treatment with anticonvulsants;
• mental retardation;
• autism;
• macro- or microcephaly (large or small skull);
• Skeletal disorders - scoliosis, spine kyphosis, deformities of the feet;
• loss of hair, dysplasia, irregular face structure.

Incontinence of pigment

Fakomatoz, associated with the pathology of the X-chromosome, and therefore, manifested primarily in women (the ratio of women and men is 2:).

The disease begins in the first months of life with a rash in the form of vesicles of various sizes. Periodically, there are new rashes. The rash has the appearance of lines or bands. Vesicles dry up, crusts form, and then pigmentation in the form of cobwebs, strips, marble spots, curls, bizarre divorces remains in their place. Pigmentation is grayish or bluish. As you grow older, the pigmentation turns pale and becomes less noticeable.

Dysplasia of the teeth, nails, and hair in the form of patches of baldness are possible.

From neurological disorders, the disease is accompanied by a violation of mental development, epileptic seizures, increased intracranial pressure, weakness and violation of muscle tone in extremities.

In 30% of patients there are eye symptoms in the form of strabismus, cataracts, atrophy of the optic nerve.

Albinism

This kind of phakomatosis is also genetically conditioned. The mutation leads to the absence of a pigment - melanin. If it is absent only in the iris, then this is the eye form of albinism. If the pigment is not present in the iris, or in the hair, or in the skin, then this is an ocular form. At the same hair, eyelashes, eyebrows look whitish, the skin is pale or pink due to translucent vessels. The eyes will not necessarily be red, as is commonly believed. They can have a completely natural color. A red tint (as with a photo with a flash) appears as a result of the reflection of light from the retina.

The disease occurs with a frequency of 1-20 cases per 100 000 population. He is subject to all races on all continents.

In addition to changes in the color of the eyes, skin and hair, albinism is manifested by nystagmus (trembling involuntary movements of the eyes), nodal movements of the head, visual impairment. Such people do not tolerate sunlight because their skin does not know how to sunbathe, but completely absorbs rays, which can lead to burns and even skin cancer.

Rude and obvious neurological disorders are usually not detected, albinos do not differ from ordinary people in this sense. Their mental and mental development corresponds to the norm.

Treatment of phacomatosis

This group of diseases, to date, is incurable. The whole range of methods of care for such patients is classified as symptomatic.

Neurofibromas of large size are surgically removed, but they tend to recur. Laser and cryosurgery are also used (in the treatment of hemangiomas, retina of the eye). In the selection of methods of treatment are guided by individual characteristics of the course of the disease.

Of the medicines often used:

• anticonvulsants;
• antioxidants and multivitamin complexes;
• neurometabolites for improving brain function;
• means for reducing intracranial pressure;
• antibiotics and immune medications (especially with the Louis-Bar syndrome).

In the case of degeneration of tumors into malignant tumors, appropriate treatment is provided by the oncologist.

Fakomatosis is a large group, mainly of genetically determined diseases. Defect is formed during pregnancy and is realized after birth. The skin, the nervous system, and sometimes the internal organs are affected. In some cases, the disease immediately manifests itself (for example, pigment incontinence, albinism), in others - decades can pass decades of asymptomatic flow (type II neurofibromatosis). The phacomatosis is incurable, but many patients are partially helped by symptomatic treatment.