Riley-Day syndrome is a severe, genetically determined sensory-autonomic neuropathy. The symptom complex includes a combination of dysphagia, vomiting, decreased surface sensitivity, autonomic dysfunction, ataxia, insufficient secretion of lacrimal fluid. To diagnose Riley-Day syndrome, it helps to conduct a histamine test and DNA analysis, the exclusion of other pathology using neurosonography or MRI. The therapy is symptomatic, aimed at relieving vomiting, compensating for fluid losses, normalizing blood pressure, reducing muscle hypotension, neuropsychological correction.
General information
Riley-Day syndrome is named after the American pediatricians who first described it in 1949. The eponymous name was introduced in 1964. In addition, the terms “familial dysautonomia” and “hereditary sensory-autonomic neuropathy type III” (NSWR type III) are used in relation to this pathology. Riley-Day syndrome is prevalent mainly among Ashkenazi Jews. In their population, it occurs with a frequency of 1 case per 10-20 thousand population. The disease is a combination of severe autonomic dysfunction and sensitive disorders, in 40% of cases it is accompanied by convulsive paroxysms, which leads to a delay in the psychomotor development of the child. Due to the lack of specific therapy, up to a quarter of patients die during the 1st year of life. Due to the polymorphism of manifestations and the complexity of treatment, familial dysautonomia is a serious problem for modern neurology and pediatrics.
Causes
Currently, the pathogenesis of familial dysautonomia is not known. It is assumed that the substrate of the disease is metabolic disorders, in particular norepinephrine, the basic neurotransmitter of sympathetic synapses. According to another hypothesis, Reilly-Day syndrome is associated with excessive accumulation of acetylcholine in neuromuscular synapses and blocking the passage of nerve impulses to muscle fibers. Pathomorphologically, degenerative changes and demyelination zones are observed in the synaptic ganglia, the posterior pillars and roots of the spinal cord, the vestibular and trigeminal nerves, in the reticular formation, and the brainstem.
Recent research in the field of genetics has allowed us to establish that the hereditary nature of the pathology is determined by a genetic defect in the 9q31 locus of the 9th chromosome. In 95.5% of patients, a similar defect of the GKVKAR gene was detected, in the rest 2 more rare mutations were identified. Reilly-Day syndrome is inherited by an autosomal recessive mechanism. If both parents are carriers of a pathological gene, then the probability of having a sick child is 25%.
Symptoms
As a rule, clinical manifestations of familial dysautonomia appear immediately after the birth of a child. Children cry weakly, they have generalized muscle hypotension and decreased reflexes of newborns. At first, problems with feeding come to the fore: difficulty swallowing (dysphagia) and sucking, cyclic regurgitation, frequent vomiting are noted. Aspiration pneumonia may occur against the background of dysphagia. Vomiting can provoke gastric bleeding; in such cases, an admixture of blood is observed in the vomit.
Problems with nutrition persist throughout the entire childhood period, can lead to the development of hypotrophy and the lag of the child in physical development. At the age of 5 years, children have paroxysms of apnea, often leading to the development of syncopal states (fainting). 40% of children have tonic-clonic generalized epiprimes, which in some cases are associated with hyperthermia or hypoxia caused by respiratory disorders.
Vegetative dysfunction is manifested by hyperhidrosis, abundant salivation, thermoregulation disorder with periodic causeless rises in body temperature (sometimes hypothermia), lability of blood pressure (transient arterial hypertension, arterial hypotension when moving to an upright position), constant cooling, cyanosis and trophic changes in the skin of the distal extremities, alternating diarrhea and constipation, decreased secretion of tears.
The last symptom becomes apparent after 3 months of age. Normally, during this period, crying begins to be accompanied by lacrimation, and in children with Riley-Day syndrome, lacrimation is absent or sharply reduced. A decrease in tear production often leads to ulcerative keratitis. Due to the disorder of autonomic innervation of peripheral vessels, erythematous spots periodically appear on the skin. At the age of 4-5 years, prolonged vegetative crises lasting up to several days occur. They are accompanied by profuse sweating, vomiting every 25-30 minutes, anxiety, an increase in blood pressure, the appearance of erythema mottled.
Sensitivity disorders are manifested by the absence of pain and temperature perception of the skin and the ability to distinguish several identical stimuli simultaneously affecting different areas of the skin surface. Deep types of sensitivity (vibratory, musculoskeletal feeling) are less disturbed. Sensory disturbances contribute to the frequent traumatism of the child. With age, vegetative and sensory disorders are joined by ataxia, which becomes noticeable when the child begins to walk. Gait is characterized by slowness and clumsiness, which is probably due to sensory disorders.
Often, Riley-Day syndrome is accompanied by some delay in mental development, a moderate decrease in the cognitive sphere. Children (especially girls) have a later puberty. Indistinctness and nasal tone of speech are typical. With age, polyneuropathies join the clinical picture of the disease. Most patients develop progressive scoliosis. Children are often ill because they are susceptible to various infectious processes. Especially often they have inflammatory lesions of the respiratory tract: tracheobronchitis and pneumonia.
Diagnostics
The diagnosis is based on a characteristic combination of clinical symptoms (autonomic dysfunction, sensory disorders, decreased lacrimal secretion, vomiting, ataxia) and their occurrence in early childhood. To assess the mental development of the child, a neuropsychological examination is prescribed. From additional studies, the histamine test is of diagnostic value. Normally, intradermal administration of histamine solution causes skin redness by 1-3 cm around the injection site. The absence of any reaction confirms the Riley-Day syndrome.
Hardware studies are carried out in order to exclude other pathology of the nervous system. Infants are prescribed neurosonography through the fontanelle, older children — MRI of the brain. With familial dysautonomia, these examinations do not reveal any pathological abnormalities. Differential diagnosis is performed with other hereditary polyneuropathies and congenital immunodeficiency. Patients are recommended to consult a geneticist and DNA diagnostics. Genealogical research confirms the autosomal recessive type of inheritance.
Treatment and prognosis
Specific therapy has not been developed because there are no clear ideas about the pathogenesis of the disease. Perhaps the future treatment of familial dysautonomia is in the field of gene therapy. To date, symptomatic supportive treatment is being carried out, which requires the participation of several specialists at once: a neurologist, gastroenterologist, orthopedist, ophthalmologist, pediatrician. In case of vomiting, compensation for lost fluid is carried out by infusion therapy, chlorpromazine is prescribed as an antiemetic. With arterial hypertension, hypotensive therapy is carried out. To reduce muscle hypotension and prevent the development of scoliosis, physical therapy, classes on special simulators, massage are recommended. With a delay in mental development, neuropsychological correction is indicated.
Unfortunately, Riley-Day syndrome has a disappointing prognosis. About a quarter of cases die in early childhood due to severe nutritional disorders or intercurrent infections mainly of the respiratory tract. In some cases, with complex symptomatic therapy and adequate care, patients live to the age of 35.
