He Riley-Day syndrome , Also known as family dysautonomia, is an autonomic sensory neuropathy of origin Heredity that generalizes nervous affectation that results in an autonomic and sensorial dysfunction (Axelrod, Rolnitzky, Gold von Simson, Berlin and Kaufmann, 2012).
In addition to this name, this type of disease can be known as familial dysautonomia, hereditary type autonomous sensory neuropathy III (NSAH III) (National Institutes of Health, 2016).
At the genetic level, Riley Day syndrome is produced by the presence of a mutation on chromosome 9, specifically in the localization (9q31) (Orphanet, 2007).
At the clinical level, it can lead to a wide variety of signs and symptoms, all of them resulting from sensory dysfunction and significant involvement of the autonomic nervous system (Orphanet, 2007).
Some of these include altered breathing, digestion, production of tears, pressure Arterial, stimulus processing, taste, pain perception, temperature, etc. (Genetics Home Reference, 2016).
The diagnosis of this pathology is made based on the clinical observation of the medical alterations, in addition, for its confirmation, the Use of a genetic study (Orphanet, 2007).
Riley Day syndrome presents a high rate of morbidity and portality. However, although there are no curative treatments, (National Institute for Neurological Disorders and Stroke, 2015) Improve the medical prognosis, survival, and quality of life of affected individuals (Axelrod et al., 2012).
Definition
Riley Day syndrome is a type of autonomic sensory neuropathy of hereditary genetic origin that is part of peripheral neuropathies, Resulting in dysfunction of the sensory and autonomic nervous structures as a consequence of a genetic alteration (Esmer, Díaz Zambrano, Santos Díaz, González Huerta, Cuevas Covarrubias and Bravo oro, 2014).
The Peripheral neuropathy , Also known as peripheral neuritis, is the term used to classify a group of disorders that occur As a result of the presence of one or more lesions in the nervous system, due to the suffering or development of damages in the nerves Peripheral devices (Johns Hopkins Medicine, 2016, Pai, 2009).
This type of alterations frequently produce episodes of localized pain in the extremities, Hypotonia , Muscle spasms and atrophy, loss of Balance, motor incoordination, loss of sensitivity, Paraesthesia , Changes in sweating, dizziness, loss of consciousness or dysfunction Gastro-intestinal, among others (American Chronic Pain Association, 2016).
Specifically, in the peripheral nervous system , Its nerve fibers distribute from the brain and spinal cord To the entire body surface (internal organs, skin areas, limbs, etc.).
Thus, its essential function is the bidirectional transmission of motor, autonomic and sensory information (Foundation for Pediatric Neuropathy, 2016; Foundation for Pediatric Neuropathy, 2016).
Classification
There are different types of peripheral neuropathies:
- Motor neuropathy
- Sensory neuropathy
- Autonomic neuropathy
- Mixed or Combined Neuropathy (Foundation for Peripheral Neuropathy, 2016)
According to the function of the type of nerve fiber that is affected:
- Motor nerves
- Sensory nerves
- Autonomic nerves (National Institute of Neurological Disorders and Stroke, 2016).
In the case of Riley Day syndrome, the Peripheral neuropathy Is of autonomic sensorial type.
Thus, in this pathology, both the nerve terminals and the autonomic nerve terminals (National Institute of Neurological Disorders and Stroke, 2016) are affected or injured.
The nerve terminals are essentially responsible for the transmission and control of perceptions and sensory experiences, while the autonomic nerve terminals are responsible for the transmission and control of all information related to the organism's non-conscious or involuntary processes and activities
Generally, sensory-autonomic neuropathies usually affect fundamentally the thresholds of sensory perception, transmission and Processing of stimuli related to pain, control and regulation of respiration, cardiac function and gastrointestinal function (Foundation for Peripheral Neuropathy, 2016).
Riley-Day syndrome was initially described by Riley et al. In 1949. In his clinical report he described 5 childhood cases In which he identified profuse sweating, an excessive reaction to anxiety with the development of hypertension , Absence of tears or Pain on temperature changes (Norcliffe-Kaufmann and Kaufmann, 2012).
In addition, this group of researchers observed this set of clinical symptoms in a specific population, in children of Jewish ancestry, who Made suspicion of a genetic origin or etiology (Norcliffe-Kaufmann and Kaufmann, 2012).
Later, in 1952 the initial clinical presentation was expanded with 33 more cases and the name assigned to this pathology was the one of Family dysautonomia (GIVES) (Norcliffe-Kaufmann and Kaufmann, 2012).
However, it was not until 1993, when the specific genetic factors involved in Riley-Day syndrome were discovered (Blumenfeld et al., 1993; Norcliffe-Kaufmann and Kaufmann, 2012).
Finally, Riley-Day syndrome is categorized as a neurological affection in which damage and lesions can be distinguished in axons or Cytoskeleton Of the autonomic and sensorial neurons (Esmer et al., 2014).
Frequency
Riley Day syndrome is a rare disease, has a specific prevalence in people of Jewish ancestry, especially in Europe. This (Orphanet, 2007).
Thus, different studies have estimated its incidence in approximately one case for every 3,600 births (Axelrod and Gold-von Simson, 2007).
Although this pathology is hereditary and therefore present from birth, a higher frequency has not been identified in one of the (Orphanet, 2007).
In addition, the average age of people with Riley-Day syndrome is 15 years, because the probability of reaching 40 years of age in The time of birth does not exceed 50% (Familial Dysautonomia Foundation, 2016).
Typically, the major causes of death are related to pulmonary pathologies and complications or sudden death due to deficits (Familial Dysautonomia Foundation, 2016).
Signs and symptoms
Riley-Day syndrome results in a pattern of complex neurological involvement, accompanied by Cardiovascular autonomic functioning, ventilatory response, pain, perception of temperature or taste, swallowing, walking or Expression of muscle reflexes (Norcliffe-Kaufmann and Kaufmann, 2012).
Clinical findings may vary significantly among affected individuals, however, the most common ones usually include (Axelrod and Gold-von Simson, 2007):
Musculoskeletal manifestations
Physical characteristics are often not obvious at birth, so Body dysmorphic Tend to develop over time due to Fundamentally to the suffering of a bony formation and deficient muscular tone.
In the case of facial configuration, a peculiar structure seems to develop with significant flattening of the upper lip, especially Evident when smiling, prominent jaw and / or erosion of the nostrils.
In addition, short stature or development of severe scoliosis (curvature or deviation of the spine) are some of the medical findings more frequent.
Autonomous manifestations
The alterations in the autonomic area are significant and constitute some of the most disabling symptoms for people suffering from Riley-Day.
- Alacrimia : Partial or total absence of tearing. This medical condition is one of the cardinal symptoms of Riley-Day, since tears are often absent from emotional crying from the moment of birth.
- Food deficit : In almost all affected there is a significant difficulty to eat normally efficient.
This is mainly due to factors such as poor oral coordination, gastroesophageal reflux (Stomach contents return To the esophagus due to poor closure), abnormal intestinal motility, recurrent vomiting and nausea, among others.
- Excess secretions : It is possible to observe an excessive increase of the corporal secretions, like the Diaphoresis (Sweating (Excessive production of juice and gastric mucosa), bronchorrhea (excessive production of bronchial mucosa), and / or sialorrhea (production of Excessive saliva).
- Respiratory distress : Hypoxia or oxygen deficiency in the body is one of the most frequent symptoms of the syndrome Riley-Day. Besides, the Hypoxemia Or deficit of oxygen pressure in the blood is also common.
On the other hand, many individuals can develop Chronic lung diseases such as pneumonia , By aspiration of substances and / or foods.
- Dysautonomic crisis : Brief episodes of nausea, vomiting, tachycardia (rapid and irregular heartbeat), high blood pressure (Abnormal elevation of blood pressure), hyperhidrosis (excessive and abnormal sweating), increase in body temperature, tachypnea Abnormal respiratory rate), pupillary dilatation, among others.
- Heart alterations : In addition to those mentioned above, it is so often observed Orthostatic hypotension (decrease Sudden blood pressure resulting from postural change) and bradyrhythmia (abnormally slow heart rate). In addition, it is also common to observe An increase of the blood pressure (hypertension) before emotional or stressful situations.
- Sincopes : In many cases, a temporary loss of consciousness may occur due to a sudden reduction of the flow Blood.
Sensory Manifestations
Alterations of the sensory area are usually less severe than those related to the musculoskeletal configuration or the autonomic function. Some Of the most common in Riley-Day syndrome include:
- Episodes of pain : Elevated perception of pain is common in individuals with Riley-Day syndrome, especially Associated with the skin and bone structure.
- Alteration of sensory perception : An abnormal perception of temperature, vibration, pain, or The taste, although it is never completely absent.
Other neurological manifestations
In all or a large number of cases, it is possible to identify a generalized developmental delay, characterized Late acquisition of gait or expressive language.
In addition, the Neuroimaging Indicate the development of neurological involvement and a Cerebellar atrophy Significant that, among other symptoms, May contribute to worsening of balance control, motor coordination or macha.
Causes
Family dysautonomia or Riley Day syndrome has a genetic etiological nature. Specifically, it is associated with a mutation of the HSAN3 gene (IKBKAP) located on chromosome 9, at location 9q31 (Orphanet, 2007).
The IKBKAP gene is responsible for proportionally lacking biochemical instructions for the production of a protein called the IKK-complex. Thus, in the case of Riley-Day syndrome, the absence or deficient production of this leads to the signs and symptoms characteristic of this pathology (Genetics Home Reference, 2016).
Diagnosis
The diagnosis of this pathology, like other hereditary neurological disorders, is based on the clinical recognition of signs and Cardinal symptoms of the pathology described above (Axelrod and Gold-von Simson, 2007).
It is essential to make a differential diagnosis to rule out the presence of other diseases other than Riley Day syndrome and to specify The symptomatology that suffers the affected person (Orphanet, 2007).
In addition, it is advisable to perform a genetic study to confirm the presence of a genetic mutation compatible with this disease (Axelrod and Gold-von Simson, 2007).
Treatment
At present, it has not yet been possible to identify a curative treatment for this pathology of genetic origin. Usually some drugs are used as Diazepam , Metoclopramide or chloral hydrate, to alleviate some of the symptoms (National Organization for Rare Disorders, 2007).
In addition, the use of physical and occupational therapy is also recommended for the management of musculoskeletal complications.
On the other hand, Compensatory measures of feeding or breathing are essential to compensate for deficits and Improve Life Quality Of the people affected (National Organization for Rare Disorders, 2007).
Therefore, the treatment is essentially supportive palliative, oriented to the control of alacrimia, respiratory and gastrointestinal dysfunction, Cardiac abnormalities, or neurological complications (National Organization for Rare Disorders, 2007).
In addition, in cases of dysmorphia and severe musculoskeletal disorders, surgical approaches may be used to correct some alterations, Especially those that inhibit normalized caporal development and the acquisition of motor skills and abilities.
References
- ACPA. (2016). Peripheral Neuropathy. Retrieved from the American Chronic Pain Association: https://theacpa.org/condition/peripheral-neuropathy
- Axelrod, F., & Gold von Simson, G. (2007). Hereditary sensory and autonomic neuropathies: types II, III, and IV. Obtained from BioMed Central:
- Axelrod, F., Rolnitzky, L., Gold von Simson, G., Berlin, D., & Kaufmann, H. (2012). A Rating Scale for the Functional Assessment of Patients with
Patients with. The Journal of Pediatrics, 1160-1165. - Esmer, C., Díaz Zambrano, S., Santos Díaz, M., Gonzélez Huerta, L., Cuevas Covarrubias, S., & Bravo Oro, A. (2014). Autonomic sensory neuropathy
Hereditary type IIA: early neurological and skeletal manifestations. An Pedriatr (Barc), 254-258. - FD. (2016). FD Fact Sheet. Retrieved from the Dysautonomia Foundation: http://www.familialdysautonomia.org/facts.htm
- FPN. (2016). What Is Peripheral Neuropathy. Retrieved from"The Foundation for Peripheral Neuropathy:
- Genetics Home Reference. (2016). Familial dysautonomia. Retrieved from"Genetics Home Reference:
- NIH. (2015). Dysautonomia Information. Retrieved from the National Institute of Neurological Disorders and Stroke:
- NIH. (2016). Neuropathy. Retrieved from the National Institute of Diabetes and Digestive and Kidney Disease:
- Norcliffe-Kaufmann, L., & Kaufmann, H. (2012). Familial dysautonomia (Riley-Day syndrome): When baroreceptor feedback fails. Autonomic Neuroscience: Basic and Clinical, 26-30.
- NORD. (2007). Dysautonomia, Familial. Retrieved from the National Organization for Rare Disorders:
- Orphanet. (2007). Family dysautonomia. Obtained from Orphanet:
- Father, S. (2009). Peripheral Neuropathy.
- UMM. (2016). Riley-Day syndrome. Retrieved from the University of Maryland Medical Center: http://umm.edu/health/medical/ency/articles/rileyday-syndrome