| Treatment of Rett syndrome | |
|---|---|
| Specialty | Clinical Psychologist, Psychiatry, Pediatrics |
There is no cure for Rett syndrome. Treatment is directed towards improving function and addressing symptoms throughout life. A multi-disciplinary team approach is typically used to treat the person throughout life. This team may include primary care physician, physical therapist, occupational therapist, speech-language pathologist, nutritionist, and support services in academic and occupational settings.
Treatment of Rett syndrome includes:
Because of the increased risk of sudden cardiac death, when long QT syndrome is found on an annual screening EKG it is treated with an anti-arrhythmic such as a beta-blocker. There is some evidence that phenytoin may be more effective than a beta-blocker. [1]
Trofinetide, sold under the brand name Daybue, is a medication used for the treatment of Rett syndrome. [2] It is taken by mouth. [2]
The most common adverse reactions include diarrhea and vomiting. [3]
Trofinetide was approved for medical use in the United States in March 2023. [2] [3] [4] [5] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication. [6]The symptoms of RTT severely limit individuals from independently taking part in meaningful activities in their day-to-day lives. [7] As a result, most people with this disorder are very dependent on their caregivers in most areas of their lives. [8] Occupational therapists (OTs) try to find ways to encourage these individuals to take part in activities that are meaningful to them, as this has been shown to improve health and well being. [8] The goals of occupational therapy interventions are to maintain or improve the functional abilities of individuals with this disorder. It is important to remember that services for each individual with RTT can differ greatly. OTs work together with clients and their families to help clients achieve their unique goals. OTs not only provide direct services for the client and families, but they can also connect family members to information and resources outside of occupational therapy. Services provided may include but are not limited to: maintaining motor and daily living skills and maintaining cognitive and communication functioning.
Goals of physical therapy treatment include improving and maintaining function by addressing impairments in mobility, posture, cardiovascular endurance, coordination, and balance. [9] A physical therapist can also fit braces, casts, and assistive devices as necessary to those with Rett syndrome to address bony malformations, and stabilize joints. [10]
Hydrotherapy is an alternative is a branch of both physiotherapy and occupational therapy. [11] There is some evidence to suggest that hydrotherapy can improve movements, feeding skills, motor skills and walking balance in children with Rett syndrome. [12] [13]
Some symptoms such as involuntary stereotypical hand movements can make eating a very difficult self-care task for individuals with RTT. One way OTs address this problem is by educating and encouraging caregivers to practice guided feeding. Guided feeding involves having the individual with RTT grasp the spoon, with the caregiver's hand on top of the child's to guide eating movements. [8] The purpose of this therapy is to encourage involvement in this important self-care activity, particularly for individuals with severe cases of RTT. [8] Signals such as opening their mouth in preparation for food, rejecting unwanted foods, and spending an increased amount of time watching their helpers, indicates that guided feeding therapy can increase engagement in eating in some cases. [8]
Another way OTs may increase involvement in eating and hand function in general is by making hand splints. Research suggests that hand splints place the hand in a more functional position and prevent repetitive motion; this leads to better finger and spoon-feeding skills. [8] Although fully independent feeding is rare for individuals with RTT, hand splints allow them to become more engaged in eating. Alternatively, active participation can be encouraged through the use of elbow splints, which decrease the repetitive stereotyped arm movements characteristic of RTT. As a result, socialization and interaction with the environment during eating may increase. [8]
Other adaptations to eating include altering the pace of feeding and recommending specific foods and textures that the individual is easily able to swallow, which is difficult done by a speech therapist. [14] In addition, OTs provide adaptive devices such as cuffs and loops (to help the individual hold their utensils), large handled utensils that are easier to grasp, and cups with lids to assist with eating and address proper nutrition. In general, all of these therapeutic methods are aimed at improving the quality of the swallowing response and general eating performance. [15] Although parental and self-reports indicate good appetite in most of the population, weight loss is an issue that many individuals with RTT face. This suggests the importance of proper nutritional education for both the individual and their caregivers. This education, along with meal management and planning, may be provided by the Speech and language therapist often in consultation with OT, a nutritionist or dietitian.
Seating and positioning the individual can also affect how they do daily tasks such as eating, dressing, and grooming. For an individual to engage in these tasks, OTs may adjust and modify tables, chairs, and wheelchairs to promote positive interactions within different social environments. [16] OTs are also involved in educating families on various adaptive devices that can promote comfort, ease of use, and safety for children and their caregivers. Some of the commonly used adaptive devices include bath benches, toilet chairs, and movable shower heads. [17] Finally, occupational therapists work with children and their families to develop skills required to brush their teeth and hair, bathe, and dress. [16]
If children with RTT are in school during the day, OTs PTs and speech pathologists can play a role in teaching special education assistants (SEAs) about the self-care needs of the child. This can include education on feeding techniques that are suitable for the child, proper mechanics of lifts and transfers, as well as toileting techniques and routines.
Children with RTT need to engage and participate in leisure activities just like typically developing children. Play is the primary activity of childhood, and is considered both a form of leisure and productivity. It is essential to development as it facilitates cognitive, physical, social, and emotional well-being. [18] Play is an activity with multiple purposes; it provides opportunities for a child to grow and develop, explore, learn, build relationships, and develop interests. Because play is so central to a child's development, therapists try to find ways that allow these children to play. The support team, including the special education teacher, OT, PT, and speech pathologist, work with clients and their family to make sure that the interventions focus on play activities that are meaningful to the child, whether it be arts, music, sports, computer games, and/or maintaining social relationships.
There is no set list of the services that are provided in terms of leisure activities, as the team works with the child to find activities that he or she finds enjoyable and important. [17] Some examples of how the team may facilitate play include adapting bicycles, providing switches so that the child can turn on music/video players, and connecting the child and her family to resources and programs within the community. [17]
In addition, some therapeutic activities are regarded as highly enjoyable for children with RTT and can be considered a form of play as well as therapy. One such activity that children with RTT may participate in is aquatic, or swimming therapy. The aims of swimming therapy are to promote relaxation, improve circulation, strengthen muscles, and improve coordination and balance. [7] Aquatic therapy is an enjoyable and relaxing activity for children with RTT, and in some cases therapy has been associated with a decrease in abnormal hand movements and an increase in goal directed hand movements and feeding skills. [7] Examples of other activities that are therapeutic and enjoyable include horseback riding therapy and music therapy.
Individuals with RTT often do not develop, or lose the ability to communicate through speech. [19] If these individuals cannot communicate with their family and caregivers it makes it very difficult for them to participate in daily activities as they also have severe physical difficulties. Speech-language pathologists plan communication interventions that aim to increase the skills needed for carrying out self-care, productivity, and leisure tasks. Studies suggest that only twenty percent of the people with RTT had the use of words, and most of these words were used out of context and without meaning. [19] As a result of their lack of spoken language, individuals with RTT can benefit from Augmentative and Alternative Communication (AAC), which are communication methods used in place of speech. Examples of AAC may be written language, body language, and facial expressions. [17] It is within the scope of practice for speech-language pathologists to provide a thorough AAC evaluation taking into consideration all factors such as sensory, motor, kinesthetic, speech, and receptive as well as expressive language in its verbal and non-verbal forms.
The Speech and Language Therapist will assess the person for signs of respiratory compromise and other symptoms of swallowing difficulty, and negotiate management strategies based on balancing and maintaining the persons physical safety, psychological well-being and quality of life. The speech pathologist works with the family, caregivers and client to improve communication and social interaction. This may include using an aac device, eye contact or using their body to communicate their wants and needs to others.
Individuals with RTT often do not develop, or lose the ability to communicate through speech. [19] If these individuals cannot communicate with their family and caregivers it makes it very difficult for them to participate in daily activities as they also have severe physical difficulties. Speech-language pathologists plan communication interventions that aim to increase the skills needed for carrying out self-care, productivity, and leisure tasks. Studies suggest that only twenty percent of the people with RTT had the use of words, and most of these words were used out of context and without meaning. [19] As a result of their lack of spoken language, individuals with RTT can benefit from Augmentative and Alternative Communication (AAC), which are communication methods used in place of speech. Examples of AAC may be written language, body language, and facial expressions. [17] It is within the scope of practice for speech-language pathologists to provide a thorough AAC evaluation taking into consideration all factors such as sensory, motor, kinesthetic, speech, and receptive as well as expressive language in its verbal and non-verbal forms. OTs are consulted in this process, to determine motor or sensory skills and deficits, as well as seating and positioning. This evaluation will result in a recommendation of AAC systems, which often include low-technology, mid-technology and high-technology systems. A speech-language pathologist will also provide therapy to help the client with RTT to access and learn the systems once they are procured, through private funds, school districts, or private/public medical insurance.
Some of the AAC systems common to individuals with RTT include eye-gaze boards, communication boards, switches, or voice output communication devices. Speech-Language Pathologists (SLPs), often with specialized AAC training and knowledge, provide education and training to families, educational teams, and other communication partners on these tools. AAC options are often divided into three levels of technology: no technology, low technology, and higher technology (mid-tech or high-tech, consisting of systems requiring the use of a battery or powercord). [17] The simplest way to communicate is through ‘no technology’ or "unaided" methods in which the individuals with RTT indicates a response (i.e., points, blinks their eyes, raises their eyebrows) to indicate a response. The second type are ‘low technology’ communication systems which often include using pictures, symbols, and/or objects placed on a board. A person then uses eye gaze or finger pointing to show his or her choices. Communication boards can be set up by the SLP and OT in both home and school environments. The third and most complex level of technology is ‘higher technology’. Some of the more commonly used technological devices include voice output systems and computer communication software. [17] Low-technology, mid-technology, and high-technology systems are considered "aided" systems, as they require the use of an object other than one's own body to communicate. The SLP and OT work with the child, as well as the family, caregivers, and school assistants to encourage the child to communicate as much as possible by using all these different tools.
Studies, funded by the International Rett Syndrome Foundation, demonstrate that neurological deficits resulting from loss of MeCP2 can be reversed upon restoration of gene function. These studies are quite exciting because they show that neurons that have suffered the consequences of loss of MeCP2 function are poised to regain functionality once MeCP2 is provided gradually and in the correct spatial distribution. This provides hope for restoring neuronal function in patients with RTT.
However, the strategy in humans will require providing the critical factors that function downstream of MeCP2 because of the challenges in delivering the correct MeCP2 dosage only to neurons that lack it, given that the slightest perturbation in MeCP2 level is deleterious. Thus, therapeutic strategies necessitate the identification of the molecular mechanisms underlying individual RTT phenotypes and picking out the candidates that can be therapeutically targeted.
The next phase of research needs to assess how complete the recovery is. Clearly, lethality, level of activity, and hippocampal plasticity are rescued, but are the animals free of any other RTT signs such as social behavior deficits, anxiety, and cognitive impairments? Since postnatal rescue results in viability, it will be important to evaluate if even the subtler phenotypes of RTT and MeCP2 disorders are rescued when protein function is restored postnatally. This is particularly important given emerging data about early neonatal experiences and their long-term effects on behavior in adults. [20]
GW Pharmaceuticals is running a 252-subject Phase 3 clinical trial in 2019 with Epidiolex (CBD) in an attempt to treat Rett syndrome. [21]
Trofinetide is a novel synthetic analog of the amino‐terminal tripeptide of IGF-1 designed to treat the core symptoms of Rett syndrome by reducing neuroinflammation and supporting synaptic function, it has been developed by Neuren pharmaceuticals. [22] It has shown — in a phase 2 randomised double blind placebo control trial (RDBPC) — to have statistically significant and clinically relevant improvements to the baseline testing at doses of 200 mg/kg in pediatric patients. [23] A stage 3 RDBPC has been completed with a greater number of participants and over a longer time scale [24] and a new drug application for Trofinetide was submitted to the FDA in mid 2022 and accepted for priority review. [25]
Assistive technology (AT) is a term for assistive, adaptive, and rehabilitative devices for people with disabilities and the elderly. Disabled people often have difficulty performing activities of daily living (ADLs) independently, or even with assistance. ADLs are self-care activities that include toileting, mobility (ambulation), eating, bathing, dressing, grooming, and personal device care. Assistive technology can ameliorate the effects of disabilities that limit the ability to perform ADLs. Assistive technology promotes greater independence by enabling people to perform tasks they were formerly unable to accomplish, or had great difficulty accomplishing, by providing enhancements to, or changing methods of interacting with, the technology needed to accomplish such tasks. For example, wheelchairs provide independent mobility for those who cannot walk, while assistive eating devices can enable people who cannot feed themselves to do so. Due to assistive technology, disabled people have an opportunity of a more positive and easygoing lifestyle, with an increase in "social participation", "security and control", and a greater chance to "reduce institutional costs without significantly increasing household expenses." In schools, assistive technology can be critical in allowing students with disabilities to access the general education curriculum. Students who experience challenges writing or keyboarding, for example, can use voice recognition software instead. Assistive technologies assist people who are recovering from strokes and people who have sustained injuries that affect their daily tasks.
Expressive aphasia is a type of aphasia characterized by partial loss of the ability to produce language, although comprehension generally remains intact. A person with expressive aphasia will exhibit effortful speech. Speech generally includes important content words but leaves out function words that have more grammatical significance than physical meaning, such as prepositions and articles. This is known as "telegraphic speech". The person's intended message may still be understood, but their sentence will not be grammatically correct. In very severe forms of expressive aphasia, a person may only speak using single word utterances. Typically, comprehension is mildly to moderately impaired in expressive aphasia due to difficulty understanding complex grammar.
Wernicke's aphasia, also known as receptive aphasia, sensory aphasia, fluent aphasia, or posterior aphasia, is a type of aphasia in which individuals have difficulty understanding written and spoken language. Patients with Wernicke's aphasia demonstrate fluent speech, which is characterized by typical speech rate, intact syntactic abilities and effortless speech output. Writing often reflects speech in that it tends to lack content or meaning. In most cases, motor deficits do not occur in individuals with Wernicke's aphasia. Therefore, they may produce a large amount of speech without much meaning. Individuals with Wernicke's aphasia often suffer of anosognosia – they are unaware of their errors in speech and do not realize their speech may lack meaning. They typically remain unaware of even their most profound language deficits.
Occupational therapists (OTs) are health care professionals specializing in occupational therapy and occupational science. OTs and occupational therapy assistants (OTAs) use scientific bases and a holistic perspective to promote a person's ability to fulfill their daily routines and roles. OTs have training in the physical, psychological, and social aspects of human functioning deriving from an education grounded in anatomical and physiological concepts, and psychological perspectives. They enable individuals across the lifespan by optimizing their abilities to perform activities that are meaningful to them ("occupations"). Human occupations include activities of daily living, work/vocation, play, education, leisure, rest and sleep, and social participation.
Rett syndrome (RTT) is a genetic disorder that typically becomes apparent after 6–18 months of age and almost exclusively in females. Symptoms include impairments in language and coordination, and repetitive movements. Those affected often have slower growth, difficulty walking, and a smaller head size. Complications of Rett syndrome can include seizures, scoliosis, and sleeping problems. The severity of the condition is variable.
Home care is supportive care provided in the home. Care may be provided by licensed healthcare professionals who provide medical treatment needs or by professional caregivers who provide daily assistance to ensure the activities of daily living (ADLs) are met. In-home medical care is often and more accurately referred to as home health care or formal care. Home health care is different non-medical care, custodial care, or private-duty care which refers to assistance and services provided by persons who are not nurses, doctors, or other licensed medical personnel. For patients recovering from surgery or illness, home care may include rehabilitative therapies. For terminally ill patients, home care may include hospice care.
Occupational therapy (OT) is a healthcare prof that involves the use of assessment, intervention, consultation, and coaching to develop, recover, or maintain meaningful occupations of individuals, groups, or communities. The field of OT consists of health care practitioners trained and educated to support mental health and physical performance. Occupational therapists specialize in teaching, educating, and supporting participation in activities that occupy an individual's time. It is an independent health profession sometimes categorized as an allied health profession and consists of occupational therapists (OTs) and occupational therapy assistants (OTAs). OTs and OTAs have different roles, with OTs licensed to complete comprehensive occupational therapy evaluations. Both professionals work with people who want to improve their ability to participate in meaningful occupations.
Hypotonia is a state of low muscle tone, often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength. Hypotonia is a lack of resistance to passive movement, whereas muscle weakness results in impaired active movement. Central hypotonia originates from the central nervous system, while peripheral hypotonia is related to problems within the spinal cord, peripheral nerves and/or skeletal muscles. Severe hypotonia in infancy is commonly known as floppy baby syndrome. Recognizing hypotonia, even in early infancy, is usually relatively straightforward, but diagnosing the underlying cause can be difficult and often unsuccessful. The long-term effects of hypotonia on a child's development and later life depend primarily on the severity of the muscle weakness and the nature of the cause. Some disorders have a specific treatment but the principal treatment for most hypotonia of idiopathic or neurologic cause is physical therapy and/or occupational therapy for remediation.
High-functioning autism (HFA) was historically an autism classification where a person exhibits no intellectual disability, but may experience difficulty in communication, emotion recognition, expression, and social interaction.
Auditory integration training (AIT) is a procedure pioneered in France by Guy Bérard. Bérard promoted AIT as a cure for clinical depression and suicidal tendencies, along with what he said were very positive results for dyslexia and autism, although there has been very little empirical evidence regarding this assertion. AIT typically involves 20 half-hour sessions over 10 days listening to specially filtered and modulated music. It was used in the early 1990s as a treatment for autism. Since, it has been promoted as a treatment for ADHD, depression, and a wide variety of other disorders. AIT has not met scientific standards for efficacy that would justify its use as a treatment for any condition.
Speech–language pathology (a.k.a. speech and language pathology or logopedics) is a healthcare and academic discipline concerning the evaluation, treatment, and prevention of communication disorders, including expressive and mixed receptive-expressive language disorders, voice disorders, speech sound disorders, speech disfluency, pragmatic language impairments, and social communication difficulties, as well as swallowing disorders across the lifespan. It is an allied health profession regulated by professional bodies including the American Speech-Language-Hearing Association (ASHA) and Speech Pathology Australia. The field of speech-language pathology is practiced by a clinician known as a speech-language pathologist (SLP) or a speech and language therapist (SLT). SLPs also play an important role in the screening, diagnosis, and treatment of autism spectrum disorder (ASD), often in collaboration with pediatricians and psychologists.
The floortime or Developmental, Individual-differences, Relationship-based (DIR) model is a developmental model for assessing and understanding any child's strengths and weaknesses. This model was developed by Stanley Greenspan and first outlined in 1979 in his book Intelligence and Adaptation.
Neurorehabilitation is a complex medical process which aims to aid recovery from a nervous system injury, and to minimize and/or compensate for any functional alterations resulting from it.
Angelman syndrome (AS) is a genetic disorder that mainly affects the nervous system. Symptoms include a small head and a specific facial appearance, severe intellectual disability, developmental disability, limited to no functional speech, balance and movement problems, seizures, and sleep problems. Children usually have a happy personality and have a particular interest in water. The symptoms generally become noticeable by one year of age.
Classic autism, also known as childhood autism, autistic disorder, (early) infantile autism, infantile psychosis, Kanner's autism, Kanner's syndrome, or (formerly) just autism, is a neurodevelopmental condition first described by Leo Kanner in 1943. It is characterized by atypical and impaired development in social interaction and communication as well as restricted, repetitive behaviors, activities, and interests. These symptoms first appear in early childhood and persist throughout life.
Mental disorders diagnosed in childhood can be neurodevelopmental, emotional, or behavioral disorders. These disorders negatively impact the mental and social wellbeing of a child, and children with these disorders require support from their families and schools. Childhood mental disorders often persist into adulthood. These disorders are usually first diagnosed in infancy, childhood, or adolescence, as laid out in the DSM-5 and in the ICD-11.
Speech and language impairment are basic categories that might be drawn in issues of communication involve hearing, speech, language, and fluency.
Global developmental delay is an umbrella term used when children are significantly delayed in two or more areas of development. It can be diagnosed when a child is delayed in one or more milestones, categorised into motor skills, speech, cognitive skills, and social and emotional development. There is usually a specific condition which causes this delay, such as Cerebral Palsy, Fragile X syndrome or other chromosomal abnormalities. However, it is sometimes difficult to identify this underlying condition.
Autism spectrum disorder (ASD) refers to a variety of conditions typically identified by challenges with social skills, communication, speech, and repetitive sensory-motor behaviors. The 11th International Classification of Diseases (ICD-11), released in January 2021, characterizes ASD by the associated deficits in the ability to initiate and sustain two-way social communication and restricted or repetitive behavior unusual for the individual's age or situation. Although linked with early childhood, the symptoms can appear later as well. Symptoms can be detected before the age of two and experienced practitioners can give a reliable diagnosis by that age. However, official diagnosis may not occur until much older, even well into adulthood. There is a large degree of variation in how much support a person with ASD needs in day-to-day life. This can be classified by a further diagnosis of ASD level 1, level 2, or level 3. Of these, ASD level 3 describes people requiring very substantial support and who experience more severe symptoms. ASD-related deficits in nonverbal and verbal social skills can result in impediments in personal, family, social, educational, and occupational situations. This disorder tends to have a strong correlation with genetics along with other factors. More research is identifying ways in which epigenetics is linked to autism. Epigenetics generally refers to the ways in which chromatin structure is altered to affect gene expression. Mechanisms such as cytosine regulation and post-translational modifications of histones. Of the 215 genes contributing, to some extent in ASD, 42 have been found to be involved in epigenetic modification of gene expression. Some examples of ASD signs are specific or repeated behaviors, enhanced sensitivity to materials, being upset by changes in routine, appearing to show reduced interest in others, avoiding eye contact and limitations in social situations, as well as verbal communication. When social interaction becomes more important, some whose condition might have been overlooked suffer social and other exclusion and are more likely to have coexisting mental and physical conditions. Long-term problems include difficulties in daily living such as managing schedules, hypersensitivities, initiating and sustaining relationships, and maintaining jobs.
Developmental regression is when a child who has reached a certain developmental stage begins to lose previously acquired milestones. It differs from global developmental delay in that a child experiencing developmental delay is either not reaching developmental milestones or not progressing to new developmental milestones, while a child experiencing developmental regression will lose milestones and skills after acquiring them. Developmental regression is associated with diagnoses of autism spectrum disorder, childhood disintegrative disorder, Rett syndrome, Landau-Kleffner syndrome, and neuro-degenerative diseases. The loss of motor, language, and social skills can be treated with occupational therapy, physical therapy, and speech therapy.
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