Rett Syndrome

Original Editors - Sofie Bourdinon

Top Contributors - <img class="FCK__MWTemplate" src="http://www.physio-pedia.com/extensions/FCKeditor/fckeditor/editor/images/spacer.gif" _fckfakelement="true" _fckrealelement="6" _fck_mw_template="true">  

Definition/Description

Rett Syndrome is a rare progressive disorder of the nervous system, leading to impaired cognitive and physical development (Genetics Home Reference, 2013; Medline Plus, 2014). The disorder results from a non-inherited genetic mutation, with almost all cases having no family history of the disorder (Genetics Home Reference, 2013).

Epidemiology /Etiology

Rett syndrome occurs almost exclusively in girls, affecting approximately 1 in every 10,000-15,000 females (Chahrour & Zoghbi, 2007). The incidence rate in males is unknown, partly due to males with the genetic mutation rarely surviving childbirth (Genetics Home Reference, 2013). In the rare circumstance where males with Rett syndrome survive, deficits are often more severe as males do not have an additional X chromosome to compensate for the mutation (Genetics Home Reference, 2013; Medline Plus, 2014). Children with Rett syndrome typically show normal development until 6 to 18 months after birth, later followed by regression of language and motor function (Banerjee, Castro, & Sur, 2012; Genetics Home Reference, 2013). On average, the life expectancy of females with Rett syndrome ranges between 40 to 50 years old, with death often occurring unexpectedly or due to secondary causes such as pneumonia (Medline Plus, 2014; Rapp, 2006).

Most cases of Rett syndrome are caused by a non-inherited mutation on the dominant X chromosome, on the gene encoding methyl-CpG-binding protein-2 (MECP2) (Kerr, 2002; Rapp, 2006). MECP2 is important for DNA methylation and mutations of this protein result in the inability to deactivate or repress specific genes (Rapp, 2006). The ability to ‘turn-off’ certain genes is necessary for normal development and maintenance of the nervous system, with impairment in this function potentially leading to cognitive and motor deficits (Banerjee, Castro, & Sur, 2012; Kerr, 2002). The severity of Rett syndrome varies dramatically between individuals and depends on the type and location of the MECP2 mutation as well as the process of random X chromosome inactivation (Kerr, 2002). Approximately 5-10% of cases do not appear to have MECP2 mutations (Weaving, Ellaway, Gecz, & Christodoulou, 2005). Rather, a proportion of atypical cases result from mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene, with seizures occurring before 6 months of age being characteristic of this mutation (Chahrour & Zoghbi, 2007; Weaving, Ellaway, Gecz, & Christodoulou, 2005). Further research needs to be conducted in order to investigate how MECP2 gene mutations and other factors contribute to the development and severity of Rett syndrome.

Characteristics/Clinical Presentation

Rett syndrome is characterized by normal development during the first few months of life followed by regression of motor and communication skills, cognitive impairment, stereotypic hand movements, abnormal breathing, and gait abnormalities. In Rett syndrome the central nervous system is primarily affected, however it often manifests as a multi-system disorder that impacts a child’s growth, pubertal development and overall health.

Comorbidities are common in Rett syndrome, including gastrointestinal problems, scoliosis, epilepsy, unusual breathing patterns, sleep disturbances and low bone density leading to increased risk of fractures. Scoliosis is the most prevalent orthopedic comorbidity, occurring by age 15 in approximately 75% of individuals with Rett syndrome. Altered sensitivity to pain is another characteristic that individuals with Rett syndrome may experience.

Signs and symptoms of Rett syndrome include:

Developmental and language skills
• Early developmental skills usually acquired but many later than normal
• Significantly impaired communication and cognitive abilities
• Many children lose ability to speak at around 12 to 18 months
• Gross motor and receptive language acquisition often superior to fine motor and expressive language skills
• Mathematics and reading skills are delayed or absent

Apraxia 
• Inability or impaired ability to perform tasks or movements
• Deficits in movements such as eye gaze and speech
• Complex motor skills such as managing stairs or riding a bike are delayed or absent

Hand movements
• Hang wringing/squeezing, clapping/tapping, mouthing and washing/rubbing automatisms are stereotypical in Rett syndrome
• Repeatedly moving the hands towards the mouth

Breathing Irregularities
• Apnea (breath holding)
• Hyperventilation
• Air swallowing

Other neurological symptoms
• Epilepsy
• Sleep disturbances
• Tremors
• Excess salivation
• Cognitive impairments

Symptoms affecting other parts of the body
• Scoliosis
• Microcephaly (small head size)
• Small hands and feet
• Gastrointestinal problems, including reflux and constipation
• Teeth grinding, issues with chewing and swallowing
• Heart rhythm abnormalities
• Low muscle tone
• Dystonia
• Toe walking

Differential Diagnosis 

Infantile autism is the most common incorrect diagnosis made for children with Rett syndrome. Autism spectrum disorders (ASDs) and Rett syndrome have common symptomology including impaired social interaction and communication, as well as unusual behaviour or movements. Boston Children’s Hospital encourages clinicians to think of Rett syndrome as a distinct disorder that has autism- like characteristics.

Other disorders with similar symptoms to Rett syndrome must be ruled out before a diagnosis can be made.

Some of these conditions include:
• Autism
• Cerebral palsy
• Other genetic disorders
• Hearing or vision problems
• Degenerative disorders that cause the body or brain to break down
• Brain disorders caused by trauma or infection
• Prenatal brain damage

Diagnostic Procedures

Table 1: Revised Diagnostic Criteria for Rett Syndrome. Adapted from Neul et al. (2010)

Main Criteria	Required for Typical RS	Exclusion Criteria for Typical RS	Required for Atypical RS
• Partial or complete loss of acquired purposeful hand skills • Partial or complete loss of acquired spoken language • Gait abnormalities • Stereotypic hand movements	• Period of regression followed by recovery or stabilization • All main criteria and all exclusion criteria • Supportive criteria often present	• Brain injury secondary to trauma • Grossly abnormal psychomotor development in first 6 months of life	• A period of regression followed by recovery or stabilization • 2/4 of main criteria • 5/11 supportive criteria

Supportive Criteria for Atypical RS

• Breathing disturbances when awake • Teething grinding or jaw clenching • Impaired sleep pattern • Abnormal muscle tone • Peripheral vasomotor disturbances • Scoliosis • Slowed growth • Small, cold hands and feet • Inappropriate laughing • Diminished pain response • Intense eye communication

Outcome Measures

add links to outcome measures here (also see <a href="Outcome Measures">Outcome Measures Database</a>)

Examination

add text here related to physical examination and assessment

Medical Management

The medical care and management for Rett Syndrome (RS) is symptomatic and varies among each person with RS. For example, persons with RS may take antiepileptic drugs for seizures and antidepressant drugs for anxiety  Currently, there is no effective treatment available; however, there are several potential avenues under investigation. Research on MeCP2 deficient mice suggests that the effects of dopamine agonists (levodopa) may be a potential treatment on motor dysfunction in RS.

In addition to pharmacologic treatments, orthopaedic approaches may be required for the management contractures or scoliosis in efforts to optimize gait or skeletal alignment. Specifically, surgery should be considered when lateral curvatures exceed 45 degrees. Similarly, feeding disorders among persons with RS may have a gastrotomy tube inserted to prevent aspiration during feeding . Furthermore, maintaining good bone health is also an area of management for persons with RS. Both pharmacological and non-pharmacological methods to improving bone density and reducing fractures are shown to be effective. In particular, RS guidelines emphasize vitamin D supplementation and increasing levels of physical activity.

Other health care professionals also play a crucial role in the treatment of persons with RS. Some may include:
- Speech-language pathologists – treatments targeted towards developing communication skills including non-verbal forms of communication (eye gaze, symbol boards), speech and language development
- Occupational therapists – therapy focused on achieving independence with activities of daily living and control over movements

Physical Therapy Management

RS is characterized by neuromuscular limitations that require active therapeutic intervention. Moreover, physical therapy is an important part of the management of the disorder as it aims to maximize and maintain function of persons with RS. Target areas of treatment in persons with RS include low cardiovascular capacity, uncoordinated movements (ataxia), bony deformities (spine, peripheral extremities) and spatial disorientation. Physical therapy aims to improve or maintain mobility and balance, prevent or reduce bony deformities, and ultimately improve independence. Given the large variability among persons with RS, some physiotherapy goals that may be appropriate for a majority of this population include (but not limited to):

• Improve mobility and posture and reducing tone (improves feeding abilities)
• Reducing apraxia through repetitive functional movements/activities
• Increase cardiovascular fitness
• Stimulate hand use (hand splints, fine motor activities)
• Enhance coordination and balance through practice in various situations and environments
• Improve body awareness through proprioceptive training
• Other therapies including hydrotherapy and hippotherapy

Some considerations with treatment:

• Individuals with RS experience daily fluctuations in mood and function. Therefore, the intervention plan should be flexible and constantly adjusted to the patient’s state . Therapists should practice good follow-up routines regarding the client’s status and adjust interventions as needed.
• Therapy goals (intensity and pace of treatments) should be adjusted according to reaction of patient.
• Foster elements of independence by enabling the patient to have control and choice in activities
• There is no optimal timeframe to begin physiotherapy, however the earlier treatments begin, the better.

Overall, the literature suggests that preventative approaches undergoing functional therapy with a multidisciplinary team should be adopted to maintain and maximize the abilities of persons with RS.

Resources

add appropriate resources here

Clinical Bottom Line

add text here

References

<span class="fck_mw_references" _fck_mw_customtag="true" _fck_mw_tagname="references" /> see <a href="Adding References">adding references tutorial</a>.