Phacomatoses are a group of progressive genetically determined pathologies, manifested by polymorphic symptoms with predominant damage to the nervous system, skin, visual organ and accompanied by the appearance of various neoplasms of visceral organs. It is possible to diagnose phacomatoses through the efforts of many specialists and only through a comprehensive examination of the patient (MRI, CT, ultrasound, ECG, EEG, ophthalmoscopy, etc.). Treatment is symptomatic: anticonvulsant, neurometabolic, dehydration, psychotherapeutic, surgical. The prognosis depends on the form and severity of phacomatoses.
ICD 10
Q85 Phacomatoses not classified elsewhere
General information
Separate clinical variants of phacomatoses were described by various authors at the end of the XIX century. For the first time, the Dutch ophthalmologist Van der Hoove proposed to combine diseases with combined damage to the nervous system, eyes and visceral organs, accompanied by skin manifestations in the form of hypo- and hyperpigmentation, neurofibromas and angioma into one group in 1923. He also introduced the definition of “phacomatoses”.
Currently, the term “phacomatoses” is not a nosological unit and cannot be a diagnosis, it only indicates that the disease belongs to a certain group of pathologies. The most common nosologies of this group include Recklinghausen’s neurofibromatosis and tuberous sclerosis. In total, the group includes about 30 neurocutaneous syndromes, including Louis-Bar syndrome, Hippel-Lindau disease, Bonnet-Deschaume-Blanc syndrome, Sturge-Weber syndrome, Van Bogart-Divry angiomatosis, Ito hypomelanosis, pigment incontinence syndrome.
Causes
Disease is a genetic disease caused by disorders in the processes of differentiation and development of cells in the early embryonic period. With the development of genetics and DNA analysis methods, genes have been identified for some diseases, aberrations in which determine this phacomatoses. Mutations often lead to a decrease in the synthesis of factors that block oncogenesis, which is considered a probable cause of multiple tumor growth, which in most cases characterizes phacomatoses. Studies have shown that phacomatoses have mainly autosomal dominant inheritance with incomplete penetrance, due to which the disease does not manifest itself in every generation.
Pathogenesis
Violations relate mainly to the ectodermal germ leaf, which gives rise to the entire nervous tissue, the outer layers of the skin, skin appendages (nails, hair), retina, epithelium of the oral mucosa and nasal cavity. Cells that remained in the phase of permanent embryonization, i.e. did not continue their development, form congenital tumor formations — hamartomas. These embryonic tumors of various localization often accompany any phacomatoses.
Due to the fact that phacomatoses is determined mainly by a malfunction in the development of ectodermal structures, in the literature on genetic pathology, pediatrics and neurology, it is often called neuroectodermal dysplasia. However, a combination of ectodermal dysplasia with impaired differentiation of meso- and endodermal germ leaves is not uncommon in phacomatoses. Manifestations of mesodermal dysplasia are aneurysms, angiomas, rhabdomyomas, leiomyomas, bone tissue defects (for example, hip dysplasia). The most common clinical symptom of endodermal dysplasia is polyposis of various parts of the gastrointestinal tract (stomach polyps, intestinal polyps, rectal polyps).
Symptoms
A typical feature of phacomatoses is a combined polymorphic lesion of the skin, nervous system and somatic organs. Moreover, some clinical syndromes, most often neurological and dermatological, are congenital or manifest in early childhood, and others — much later. In some cases, phacomatoses is combined with congenital immunodeficiency, premature aging and /or the risk of developing malignant tumors.
Neurological manifestations
The morphology of lesions of the nervous system is reduced to the formation of tubers, cysts, subependimal nodes, neurofibromas, calcifications, areas of gliosis, atrophy or demyelination in the substance and membranes of the brain; the presence of congenital anomalies of the vessels feeding the brain (aneurysms, AVMs, angiomas). Clinically, convulsive syndrome is most often observed, which can have a different course and a large variability of paroxysms. In early childhood, West syndrome is often noted, in older children — Lennox-Gastaut syndrome, generalized and partial sensorimotor seizures, absences.
Due to epilepsy and damage to cerebral structures, phacomatoses is often accompanied by mental retardation, speech disorders, oligophrenia, abnormal behavior. Mental underdevelopment varies from debility to idiocy, the degree of its severity directly correlates with the severity and frequency of epiprimes. Often there are disorders of the cranial nerves (oculomotor disorders, hearing disorders, facial paresis, etc.), pyramidal insufficiency (more often by hemitype), extrapyramidal symptoms (athetosis, bradykinesia, hyperkinesis, tonic muscle symptoms), cerebellar ataxia, sleep disorders (somnambulism, insomnia). Behavioral disorders are variable in nature: from ADHD to autism.
Skin manifestations
Dermatological changes accompanying phacomatoses are usually detected in the first few months of life. They can be single or diffuse, variable in color and size, as a rule, asymmetric. The most common are pigmented spots, areas of hypopigmentation, dermatofibromas, neurofibromas, papillomas, shagreen plaques, angiomas.
Endocrine disorders
In some cases, phacomatoses occurs with endocrine-metabolic disorders (diabetes insipidus, hypothyroidism, obesity, delayed or premature puberty) and disorders of the vegetative sphere and trophic (brittle nails, dry skin, hair loss).
Ophthalmological manifestations
In some variants, phacomatoses includes damage to the organ of vision. Usually, ophthalmological manifestations are congenital or have an early debut. Examination of the fundus in such cases can reveal angiomatosis or retinal hamartomas, conjunctival telangiectasia. Perhaps their inapparant course or manifestation in the form of a decrease in visual acuity.
Other manifestations
Concomitant phacomatoses lesions of somatic organs are caused mainly by neoplasms developing in them. The latter usually have a benign character, but are prone to relapse and progressive growth. Often such formations are hamartomas. In addition, children with phacomatoses have a tendency to infectious diseases, which, in turn, aggravate the course of the underlying pathology.
Diagnostics
The wide variability of symptoms and their manifestation in different age periods cause the difficulties that doctors have to overcome in order to identify and verify phacomatoses. Diagnostic search is carried out by the efforts of many specialists: neurologist, pediatrician, ophthalmologist, dermatologist, cardiologist, nephrologist, gastroenterologist, geneticist, endocrinologist, etc. If phacomatoses is suspected, biochemical blood and urine analysis, genealogical research and DNA analysis, extensive instrumental and neuropsychological examination are performed.
- Neurological diagnostics. Electroencephalography allows us to determine the nature of brain epiactivity. Echo-EG reveals signs of hydrocephalus. With the help of MRI and CT of the brain, morphological changes of cerebral tissues are visualized, with the help of brain angiography or MRA — defects of cerebral vessels.
- Ophthalmological diagnostics. Ophthalmoscopy is performed without fail, it allows you to diagnose damage to the organ of vision even in the case of its subclinical course.
- Examination of internal organs. Cardiological studies include ECG and ultrasound of the heart, gastroenterological — ultrasound of the abdominal cavity, if necessary, stomach radiography, X-ray contrast examination of the small and large intestines. Kidney examination is performed using ultrasound, urography and CT.
Treatment
Drug therapy
To date, no phacomatoses has a specific treatment. Symptomatic therapy is carried out. According to the indications, anticonvulsant (valproates, levetiracetam, carbamazepine, topiramate), dehydrating (acetazolamide), neurometabolic (B vitamins, glycine) treatment is used. Often, epiprimes turn out to be resistant to anticonvulsant therapy, and therefore it is necessary to change the drug or switch to combined regimens, including 2 anticonvulsants. In the presence of episindrome, stimulating neurometabolites (gamma-aminobutyric acid, piracetam, pyritinol) are contraindicated.
Surgical treatment
According to the indications, surgical treatment is carried out, the purpose of which is to remove the resulting neoplasm. Interventions are carried out in case of suspected malignancy of the tumor, with the increase of clinical manifestations caused by it, rapid growth of education, the development of compression syndrome. If we are talking about intracerebral tumors, then the operation is performed by neurosurgeons. In case of tumors of somatic organs, appropriate specialists operate.
Psychological correction
Along with pharmacotherapy, psychocorrection plays an important role in the treatment of phacomatoses. It is aimed at developing the child’s mental and mental abilities, individual correction of existing deviations, teaching the child in an accessible format and his social adaptation. Depending on the type and degree of mental disorders, classes with a psychologist, child psychotherapy, game therapy, AVA therapy, neuropsychological correction are recommended. Psychological counseling of parents is carried out. Complex psychological support of the child is possible.
Prognosis and prevention
Basically, phacomatoses belong to prognostically unfavorable diseases. The outcome depends on the type of phacomatoses, the age at which it debuted, and the severity of the pathology. An infectious disease or injury can aggravate the course of phacomatoses.
Prognostically unfavorable factors are: early manifestation, severe episyndrome, deep oligophrenia, the development of malignant neoplasms. The death of patients occurs when there is cerebral edema, epileptic status, cancerous cachexia, sepsis due to intercurrent infection.
The main means to prevent phacomatoses is to exclude the possibility of giving birth to a sick child. For this purpose, genetic counseling of couples planning pregnancy is carried out. The probability of having a child with phacomatoses is the basis for limiting childbearing.