Rett Syndrome

Description

Other Names

MECP2 disorder

Diagnosis Coding

ICD-10

F84.2, Rett syndrome

ICD-10 for Rett Syndrome provides further coding details.

Description

Rett syndrome (RS) first appears in infancy or, more typically, early childhood and has no racial or ethnic predilection. It is a clinical neurodevelopmental syndrome seen primarily in females. Features include:
  • normal development until approximately 6 months, followed by developmental regression
  • loss of purposeful hand movements and onset of characteristic hand wringing
  • growth retardation, particularly in head circumference, which is normal at birth but becomes microcephalic
  • breathing difficulties, including hyperventilation, apnea, and air swallowing
  • seizures in approximately 90% of individuals
  • autistic behaviors, including mouthing, hand movements, sighing, and decreased verbalization
  • teeth grinding, difficulty chewing, swallowing problems
  • severe to profound mental retardation (see the Intellectual disability/mental retardation module)
  • truncal ataxia and ataxic gait
  • dystonia and spasticity
  • in older girls, scoliosis, osteoporosis, and hand and foot deformities

The American College of Medical Genetics recommends that testing for the MECP2 gene mutation should be considered in females with unexplained moderate to severe mental retardation, even without the other clinical features. See [Moeschler: 2006].

Prevalence

Overall prevalence in Australia in 2004 was approximately 1:15,000 females, and the prevalence in girls age 5-18 years was 1:11,364. ([Laurvick: 2006]) The prevalence in China is 1:17,500 females under 35 years. ([Wong: 2007])

Genetics

Most cases of RS are due to mutations in the MECP2 gene on the X chromosome, although up to 20% of girls with the clinical picture of RS will have negative MECP2 testing. However, in China up to 96% of girls with RS features have MECP2 mutations. [Wong: 2007] It has also become clear that MECP2-related disorders comprise many more clinical syndromes than RS, including atypical RS, a severe newborn encephalopathy in males, and possibly X-linked intellectual disability without other clinical features of RS. Thus, RS is a MECP2-related disorder but not all MECP2-related disorders are RS. However, RS and MECP2-related disorders are commonly used as synonymous terms. See Rett Syndrome: Genetics for more detailed information.

Prognosis

Although developmental regression occurs in RS, it is not a degenerative disorder and survival into adulthood is usual. There are however, more sudden unexplained deaths in the RS population than in the general population. The incidence of sudden unexplained deaths is higher in those girls with decreased mobility, difficult to control seizures, and swallowing problems. Sudden unexplained death may be related to heart rhythm abnormalities (including prolonged QT intervals), seizures, or choking. Overall survival in Australia was 77.8% at 25 years when assessed in 2004. [Laurvick: 2006]

Roles Of The Medical Home

As RS is a genetic disease, there is no cure or treatment for the underlying problem. However, there are many interventions that can significantly help girls with this syndrome lead healthier lives. It is important for the Medical Home to ensure that all the necessary evaluations at diagnosis and as required thereafter have been performed. Due to the complicated nature of assessment and management of girls with RS, treatment in a multi-disciplinary clinic is recommended. The multidisciplinary clinic should include various specialists such as genetics, neurology, physiatry, speech, occupational, physical therapy, and orthopedics, but not always possible. Families with girls with RS face many challenges and may be helped by social work and parent support networks (See International Rett Syndrome Association (IRSA) as well as the Resource section below).

Practice Guidelines

The IRSA offers some guidelines for scoliosis evaluation ( Scoliosis information from the IRSF) and cardiac monitoring (International Rett Syndrome Association (IRSA)). Also, [Wilson: 2000] and [Allen: 2004] offer preventative management guidelines for children with chronic conditions, although not specifically for RS.

Helpful Articles

PubMed search for Rett syndrome in children, last 3 years

Venkat A, Jauch E, Russell WS, Crist CR, Farrell R.
Care of the patient with an autism spectrum disorder by the general physician.
Postgrad Med J. 2012;88(1042):472-81. PubMed abstract

Castro J, Mellios N, Sur M.
Mechanisms and therapeutic challenges in autism spectrum disorders: insights from Rett syndrome.
Curr Opin Neurol. 2013;26(2):154-9. PubMed abstract

Lotan M, Zysman L.
The digestive system and nutritional considerations for individuals with Rett syndrome.
ScientificWorldJournal. 2006;6:1737-49. PubMed abstract

Segawa M, Nomura Y.
Rett syndrome.
Curr Opin Neurol. 2005;18(2):97-104. PubMed abstract

Nomura Y, Segawa M.
Natural history of Rett syndrome.
J Child Neurol. 2005;20(9):764-8. PubMed abstract

Clinical Assessment

Overview

If Rett syndrome (RS) is suspected, testing may be performed by the primary care provider with referral for confirmation and genetic counseling to genetics, or the family may be sent directly to genetics for testing.

Screening

There is no screening recommended for this disorder. Testing is performed for clinical symptoms suggestive of RS or in girls with unexplained MR.

Presentations

RS will affect multiple aspects of the girl's health and the family's life. RS typically presents with deceleration of head growth, beginning as early as a few months of age, and loss of previously acquired developmental skills (fine motor and communication) between 12 and 18 months. Girls with variant RS, approximately 15% of the total, do not meet all the diagnostic criteria (see below) for classic RS. Several subtypes have been suggested:
  • congenital onset RS – there is no period of normal development; delay is noted early on, or seizures begin and are followed by developmental regression
  • late onset RS – regression and/or delay are not noted until 2-4 years of age
  • RS with preserved speech and hand skills – not usually diagnosed until later, with milder symptoms
  • male RS – a severe neonatal encephalopathy or a more typical Rett-like syndrome seen in XXY males
  • provisional RS – thought to be classic RS, but in a child not old enough for the diagnosis to be made
  • atypical – early-onset seizures RS (the Hanefield variant, see [Scala: 2005])
  • the spectrum of RS continues to widen as more is learned – mild learning disabilities in females and intellectual disability in males (syndromic or non-syndromic) are also part of the MECP2-related disorders (see MECP2-Related Disorders (GeneReviews))

Diagnostic Criteria

Diagnostic clinical criteria for classic RS: [Hagberg: 2002]

Necessary:
  • Normal prenatal and perinatal history
  • Normal psychomotor development for the first six months
  • Normal head circumference at birth
  • Postnatal deceleration of head growth in most individuals
  • Loss of purposeful hand skills between age six months and 2.5 years
  • Hand stereotypies
  • Evolving social withdrawal, communication dysfunction, loss of acquired speech, and cognitive impairment
  • Impairment or deterioration of locomotion
Supportive:
  • Breathing disturbances during waking hours
  • Bruxism
  • Impairment of sleeping pattern from early infancy
  • Abnormal muscle tone associated with muscle wasting and dystonia
  • Peripheral vasomotor disturbances
  • Progressive kyphosis or scoliosis
  • Growth retardation
  • Hypotrophic, small, and cold feet and/or hands
Exclusionary:
  • Evidence of a storage disorder, e.g., organomegaly
  • Cataract, retinopathy, or optic atrophy
  • History of perinatal or postnatal brain damage
  • Confirmed inborn error of metabolism, neurodegenerative disorder, or other genetic condition
  • Acquired neurologic disorder caused by severe head trauma or infection

Diagnostic clinical criteria for variant RS (suggested) At least 3 of 6 main criteria, and 5 of 11 supportive criteria are needed [Hagberg: 2002]

Main:
  • Reduction or absence of hand skills
  • Loss or reduction of speech (including babble)
  • Hand stereotypies
  • Loss or reduction of communication skills
  • Deceleration of head growth from early childhood
  • Regression followed by recovery of social interaction
Supportive:
  • Breathing irregularities
  • Abdominal bloating or air swallowing
  • Bruxism
  • Abnormal locomotion
  • Kyphosis or scoliosis
  • Lower limb amyotrophy
  • Cold, discolored, and usually hypotrophic feet
  • Night-time screaming and other sleep disturbances
  • Inexplicable episodes of screaming or laughing
  • Apparently diminished sensitivity to pain
  • Intense eye contact and/or eye pointing

Differential Diagnosis

It is easy to confuse RS with other diagnoses, particularly if the child doesn't have all the typical features. Other causes of similar clinical findings include:
  • Autism – girls with atypical RS are frequently first diagnosed with autism.
  • Angelman syndrome – children with Angelman syndrome often have speech delay, microcephaly, and seizures, although they do not usually exhibit a developmental regression and seizures are a more prominent feature. Sometimes children with Angelman syndrome have positive testing for MECP2 mutations.
  • Cerebral palsy – sometimes older girls with spasticity and MR that have been previously diagnosed with CP are found to have RS.
  • Infantile form of neuronal ceroid lipofuscinosis (NCL) – see Neuronal Ceroid Lipofuscinosis for more information. Patients with NCL demonstrate a continuing progressive course and have ophthalmologic abnormalities (especially electroretinogram abnormalities).
  • Rett syndrome, Hanefield variant – result of CDKL5 gene mutations that produce an atypical RS variant with prominent early-onset seizures. [Scala: 2005] This is a rare mutation type for RS-like features, but should be considered if seizures occur very early in the course of the disease and MECP2 testing is negative.

Pearls & Alerts

MECP-2 related disorders

Consider testing for a MECP-2 mutation in girls with moderate or severe mental retardation even without clinical features of RS. [Moeschler: 2006]

Abnormal early development

Evidence for subtle early developmental abnormalities in girls with RS is beginning to mount. For example, see [Einspieler: 2005] and [Einspieler: 2005].

Gallstones

Gallstones are more common in the RS population than in normal children and should be considered in girls with intellectual disability presenting with abdominal distress. Conversely, consider testing for RS in girls with intellectual disabilities and gallstones.

Air swallowing

Rarely, problems with irregular breathing may be associated with air swallowing which can cause abdominal distention and increased gas and may lead to severe gastrointestinal problems (rupture and peritonitis) if not treated.

History & Examination

Developmental delay, swallowing problems, heart abnormalities, constipation, scoliosis, physical limitations (for instance problems with eye gaze, hand use for activities of daily living, mobility changes), evidence of breathing problems, spasticity and/or dystonia may all be present at the time of initial diagnosis.

Ongoing problems and new problems that are frequent in girls with RS should be inquired about with chronic care Medical Home visits. These include loss of abilities including language, fine motor, and gross motor, scoliosis, osteoporosis, breathing problems, sleep problems, seizures, and gastrointestinal problems including reflux, abdominal pain, air swallowing, and constipation. Screening should be performed for cardiac abnormalities on a regular basis. Sensory abilities should be optimized with regular screening for vision and hearing problems. Weight and growth should be monitored. If the girl is on seizure medications and/or is nonmobile, screening for osteoporosis should be considered. Calcium and vitamin D intake should be monitored. Behavioral problems and school and social functioning should be monitored.

Family History

A family history of RS is very unlikely. Approximately 99.5% of mutations are sporadic and are not repeated in the family. MECP2-Related Disorders (GeneReviews)

Pregnancy Or Perinatal History

This history is usually normal.

Current & Past Medical History

Seizures: Ask about seizure activity. Seizures are generally grand mal or partial complex and these are easy to diagnose. However, parents may also describe episodes of staring, which may be atypical absence seizures, eye rolling, or myoclonic jerks. Ask about seizure frequency and side effects of antiepileptic medications. Up to 90% of girls with RS have seizures at some time in their lives, generally after the initial regressive period, although seizures may decrease in number and sometimes stop completely in adolescence. For more information regarding seizures, see the Seizure module.

Swallowing problems are frequent in girls with RS. They may be one of the causes of malnutrition in these children and may be linked to premature death due to choking or aspiration-caused pneumonia. The first signs of swallowing problems usually appear as choking and coughing with liquids, especially water, as it is the thinnest liquid. Foods that need extensive chewing are generally not tolerated well once swallowing difficulties occur.

Breathing problems: Girls with RS typically have episodes of abnormal breathing, consisting of disorganized breathing with periods of apnea and/or hyperventilation and resulting oxygen desaturation and clinical cyanosis. These become less noticeable with age. They should not be confused with seizures. Irregular breathing does not occur in sleep so girls with RS with abnormal sleep breathing need to be evaluated for diagnoses such as obstructive sleep apnea.

Sleep problems: Many girls with RS have difficulty sleeping. Although normal breathing occurs during sleep in girls with RS, the total sleep time may be decreased, and girls with RS may show periods of prolonged wakefulness and/or sleep. Frequent night time awakenings with laughing, crying, and or screaming may occur; screaming may represent an unrelated medical problem such as reflux or seizure as well as a sleep related phenomena.

Digestive problems: Ask about constipation, gastroesophageal reflux, air swallowing, abdominal distention, and episodes of abdominal distress.
  • Constipation is a common problem and can cause weight loss and discomfort. For diagnosis and management information, see Constipation and Management and Prevention of Constipation in Children for patient management/education material.
  • Ask about symptoms of gastroesophageal reflux, which is also common. See Gastroesophageal Reflux (general).
  • Ask about air swallowing and abdominal distention.
  • Gallstones are more common in girls with Rett syndrome than in typically developing children and can be easily overlooked. Consider gallstones as well as obstruction in a girl with RS who presents with abdominal distress.

Nutritional status/growth: Family concerns regarding eating and weight should be assessed. See Nutrition and Growth in Children with CP. Assess calcium and vitamin D intake, as osteoporosis is common in this population due to underlying nutritional problems, hypotonia, decreased mobility and/or antiepileptic medications. See Osteopenia Pathologic Fractures (general) for more information.

Mobility/Orthopedic issues: Gait may become increasingly difficult due to many factors including hypertonicity and ataxia, and should be evaluated with each chronic care visit. Scoliosis should also be looked for both clinically and if there is any concern with X-rays of the spine. By early adulthood, up to 80% of girls with RS develop scoliosis to some extent. [Kerr: 2003]

Developmental & Educational Progress

Developmental history is key – there is usually a period of fairly normal development followed by a slowdown and possibly regression. Agitation and screaming fits are common in RS but, before assuming they are behavioral, medical causes such as reflux, seizures, caries, etc. should be considered. Inquire about school progress and problems.

For repeat visits to the Medical Home it is important to evaluate the child's developmental progress. Often this is most easily done by getting early intervention and school evaluations. Families may need letters from the Medical Home to request some accommodations at school such as an evaluation by the augmentative communication team.

Social & Family Functioning

Assessing family functioning and resources available for family support are an important part of the Medical Home visit. Social functioning of the girl with RS should be evaluated as well as overall family functioning. Behavior management may be a significant problem and should be inquired about.

Physical Exam

General

Look for overall interaction and use of hands for purposeful movements.

Vital Signs

HR | BP | breathing rate should be followed for evidence of autonomic dysfunction

Growth Parameters

Height and weight should be followed closely in girls with RS so that problems with undernutrition may be identified early on. If weight is decreasing or not increasing as expected, consider further assessment with a nutritionist or a feeding clinic (see Services).

Skin

Look for signs of vasomotor instability. Check for pressure sores in girls with ankle-foot orthotics or if the girl is not ambulatory.

Extremities/Musculoskeletal

Look for evidence of hand and foot deformities. Look for scoliosis.

Neurologic Exam

Check specifically for dystonia and ataxia. Check eye movements.

Testing

Sensory Testing

Vision and hearing screens should be performed regularly. Intermittent esotropia is often observed in girls with RS.

Laboratory Testing

Only as clinically indicated after genetic testing to confirm diagnosis.

Imaging

Brain imaging is not necessary in girls with RS unless specific concerns arise.

Genetic Testing

MECP2 gene testing is key to the diagnosis – working with pediatric genetics may assure prompt testing and accurate interpretation of results. See Writing Letters of Medical Necessity (general) for sample letters to obtain insurance preauthorization for MECP2 testing.

Other Testing

EEG: It is important to get an EEG if seizures are suspected clinically, and possibly if there is an abrupt change in seizure frequency. The EEG should contain both sleep and wake states during the interval recorded. They do not need to be performed routinely if there is no clinical evidence of seizures. Sometimes the only way to clarify the issue of whether certain events, such as staring, represent seizures is to do an overnight (or longer) video EEG to see if the activity being questioned is correlated with EEG seizure activity. Imaging is not needed with a classical diagnosis of Rett syndrome unless other issues arise. During early stages of RS, the EEG will often show slowing of the occipital dominant rhythm with spike or sharp wave activity during sleep, in a pattern common for, but not pathognomic of, RS. During later stages, the occipital dominant rhythm and non-REM sleep characteristics often disappear.

EKG: Because of the risk of heart arrhythmias, girls with RS should have a baseline EKG and then repeated periodically. The International Rett Syndrome Association (IRSA) recommends the first EKG should be performed by age 5 and, if normal, repeated every other year. Long QT syndrome is fairly common in this population.

Swallow study - This test is recommended if a girl with RS has swallowing problems such as choking with drinking or if the past medical history includes frequent pneumonia. Occupational or speech therapy (depending on location) can evaluate swallowing function and safety, determine if interventions (e.g., speech therapy, special feeding techniques, improved feeding position) might lead to improvements in function, and determine the safest and most efficient textures for eating. In some cases, the therapist may suggest a fluoroscopic video swallow study (also called a modified barium or cookie swallow) be part of this evaluation (we currently have no Swallow Studies service providers listed, please search our Services database for related services).

DEXA-scan: In the clinical setting of fractures, consider a DEXA scan for assessment of bone density (we currently have no Bone Densitometry/DEXA service providers listed, please search our Services database for related services).

Sleep study - Consider if there are problems with breathing during sleep, including snoring, frequent awakenings, or excessive daytime sleepiness.

Subspecialist Collaborations & Other Resources

Developmental Pediatrics (see Services below for relevant providers)

For evaluation of developmental progress and behavioral concerns

Pediatric Genetics (see Services below for relevant providers)

For diagnosis and guidance regarding prognosis, management, genetic counseling, inheritance risk and genetic risks to other family members.

Pediatric Genetic Counseling (see Services below for relevant providers)

For provision of genetic counseling, education about the condition, and discussion of recurrence risks for family members.

Pediatric Neurology (see Services below for relevant providers)

Referral to a pediatric neurologist familiar with issues of RS is generally recommended for most girls with RS. A referral to neurology may be especially helpful in differentiating seizures from other types of episodes.

Pediatric Physical Medicine & Rehab (see Services below for relevant providers)

A referral to a rehabilitation team should be considered for evaluation of abilities, in developing a program to optimize functioning, and for medical equipment evaluations.

Psychiatrist, Child-18 (see Services below for relevant providers)

For evaluation of behavior problems with consideration of possible treatment with medications

Pediatric Cardiology (see Services below for relevant providers)

For interpretation of EKGs and education/management of long QT syndrome. The IRSA recommends yearly EKGs starting at age 5.

Pediatric Gastroenterology (see Services below for relevant providers)

For evaluation of nutritional problems, swallowing problems, reflux, and constipation. A primary care provider might wish to involve a gastroenterologist if these problems have not responded to usual management.

Pediatric Orthopedics (see Services below for relevant providers)

A baseline assessment by pediatric orthopedics is recommended by the IRSA and follow-up evaluations as recommended.

Local Support Groups, Child Abuse (see Services below for relevant providers)

For evaluation of sleep disorders including sleep apnea and frequent awakenings.

Treatment & Management

Systems

Development (general)

Referral to developmental services such as speech, occupational, and physical therapy should be made for girls with RS. Girls under three should be referred to Early Intervention (see Services) and girls over 3 should seek developmental services through the schools. Although therapies are sometimes available through these means, the intensity and frequency of this therapy may not be adequate for girls with RS and private therapy should be considered. A referral to a physiatrist and team might be helpful in this regard. Augmentative communication referrals should be considered for all girls with Rett syndrome. (See Augmentative Communication (general)).

Subspecialist Collaborations & Other Resources

Pediatric Physical Medicine & Rehab (see Services below for relevant providers)

A pediatric physiatrist and team is helpful in managing disability issues and providing private therapies for speech, occupational, and physical therapies. A primary care provider can consult a physiatrist on a one-time basis or for ongoing management if the child with RS has complicated problems. See Resources for listings of therapies.

Neurology

Seizures are frequent in girls with Rett syndrome and parents of these girls should be educated regarding what to watch for. As behavioral events may be difficult to distinguish from seizures in these girls, and as seizures in RS may be difficult to control, girls with RS should be referred to pediatric neurology for initial seizure diagnosis and treatment. Abnormal random discharges on EEG not correlated with seizure activity clinically do not need to be treated with antiepileptic medication. It will then be up to the neurologist and the Medical Home to communicate regarding follow-up treatment; some seizures may be managed completely within the Medical Home model whereas others may need frequent neurology consultation. There is some evidence that topiramate may be especially effective in girls with RS and that it may help respiratory function in some. [Goyal: 2004] See [Dolce: 2013] for more information. Medications for seizures and possibly behavior to be given in school may need to be ordered and followed by the Medical Home.

Subspecialist Collaborations & Other Resources

Pediatric Neurology (see Services below for relevant providers)

Evaluation and management of seizures in girls with RS is often difficult, and if possible, referral should be made to a pediatric neurologist. As girls with RS may have seizure-like events that aren't truly seizures, it is important to have a diagnostic evaluation before treatment.

Gastro-Intestinal & Bowel Function

Reflux: Girls with Rett syndrome have a high frequency of gastro-esophageal reflux, possibly due to their difficulties with muscle coordination. Reflux may present as arching, irritability, or food refusal rather than vomiting. Treatment can be started empirically (see Gastroesophageal Reflux (general) for details of treatment) with referral to gastroenterology if symptoms continue. Treatment is generally initiated with a proton pump inhibitor. Treatment of reflux can be augmented by the use of a motility agent (metoclopromide or low-dose erythromycin) or H2 blocker but the clinician must monitor closely for side effects (particularly irritability or dystonia with metoclopromide). Medical therapy is not successful in some patients and surgical procedures may be necessary. When medical therapy is not successful, Nissen or other type of fundoplication may be recommended and can be performed laparoscopically in some cases which shortens hospital and overall recovery time. For children who do not feed orally who are poor surgical candidates, another option is moving the distal end of the feeding tube to the small intestine (ie, GJ tube or J tube). See Feeding Tubes and Gastrostomies.

Air swallowing and abdominal distention: If problematic, behavioral treatment such as decreasing the length of mealtimes and keeping the child in a sitting position to maximize burping as well as avoiding constipation may be adequate. In severe cases, measures such as gastrostomy tubes or Nissen fundoplication may be necessary.

Constipation
is common in girls with Rett syndrome and should be asked about at visits to the Medical Home. Dietary intake should be optimized for the control of constipation (high fluid and high-fiber foods). Treatment should be as needed, and management information is provided in the Constipation.

Swallowing problems may result in drooling, malnutrition, aspiration, and dental caries. If swallowing problems causes aspiration, a referral to gastroenterology or pediatric surgery for feeding tube placement should be made. If dysphagia is determined to be a problem, diets using pureed foods and thickened liquids or feeding with a gastrostomy tube may be necessary to decrease aspiration and to help with nutrition. See Power Packing (general) and Thickening Liquids & Pureeing Foods (general).

Subspecialist Collaborations & Other Resources

Pediatric Gastroenterology (see Services below for relevant providers)

For management of reflux and constipation when necessary, as well as nutritional issues. May do feeding tube placements.

General Pediatric Surgery (see Services below for relevant providers)

For feeding tubes or surgical reflux management

Nutrition/Growth/Bone

Nutrition: Causes of poor nutrition include lack of purposeful hand movement, difficulties with coordination of chewing and swallowing, and length of time for feeding. Treatment options include small frequent meals, supplementation with Pediasure, Ensure or similar formulas, and if the girl is still underweight, consideration of feeding tube placement. Referrals to nutrition early in the course of RS should be considered. See information on Formulas, Power Packing (general) and Thickening Liquids & Pureeing Foods (general) and a helpful article [Motil: 2012] on gastroenterology needs and nutrition in girls with RS.

Osteoporosis: As osteoporosis is common in girls with RS, diet should be optimized for calcium and vitamin D (see Calcium and Vitamin D.) If fractures have occurred and a DEXA scan has shown decreased bone density, consider a trial with a bisphosphonate. While palmidronate needs to be given IV once every two months, there are numerous preparations such as alendronate and risedronate that are given orally at weekly or monthly intervals. There is no long-term data regarding their use in children, and osteonecrosis of the jaw is a potential although very small risk (see individual product data) but these medicines are helpful in preventing fractures in children with cerebral palsy. [Henderson: 2002] As with administration of bisphosphonate to anyone, girls with RS need to have empty stomachs and be able to sit upright (or be positioned in an upright fashion) for 30 minutes after ingestion. The medication can be given with a small spoon of applesauce to allow it to be swallowed. Episodes of heartburn and known uncontrolled reflux are relative contraindications. See Osteopenia Pathologic Fractures (general) for more information. See [Motil: 2011] for a recent article on vitamin D deficiency in girls with RS.

Subspecialist Collaborations & Other Resources

Pediatric Gastroenterology (see Services below for relevant providers)

A visit with gastroenterology may be helpful if the girl with RS is having trouble gaining weight or swallowing and medical management or possible gastrostomy tube placement is being considered.

Nutrition/Dietary (see Services below for relevant providers)

Consider a visit with a nutritionist in a child with difficulty gaining weight.

Pediatric Endocrinology (see Services below for relevant providers)

If bone density is low and there has been a fracture history, consider referral to endocrinology.

Cardiology

Heart problems are fairly frequent in older girls with RS, usually rhythm problems with either abnormally long pauses between heartbeats or arrhythmias. Girls with RS should have regular EKGs and if abnormal be evaluated by a pediatric cardiologist, or if older by a cardiologist that is familiar with pediatric cardiac disease. Families of girls with RS and prolonged QT syndrome should know which medications to avoid (see Drugs that Prolong the QT Interval and/or Induce Torsades de Pointes Ventricular Arrhythmia) in long QT patients. If the EKG is abnormal, a pediatric cardiologist with expertise in arrhythmias should be consulted.

Subspecialist Collaborations & Other Resources

Pediatric Cardiology (see Services below for relevant providers)

Even in girls without symptoms of heart disease, a baseline visit at age 5 with an EKG and periodic follow-up is recommended. Heart arrthymias may be the cause of the rare but real cases of premature death in girls with RS.

Musculoskeletal

Girls with RS should be followed for hand and foot deformities, and scoliosis, both of which may develop during childhood and adolescence. Up to 80% of girls with RS have scoliosis in young adulthood. The scoliosis curve may develop quite quickly and bracing does not seem to be helpful to prevent it. The IRSA is gathering information regarding the incidence and treatment of scoliosis in the hope of providing consensus guidelines. See Scoliosis information from the IRSF.

Subspecialist Collaborations & Other Resources

Pediatric Orthopedics (see Services below for relevant providers)

Baseline visits with periodic follow-up are recommended to follow girls with RS.

Mobility/Function/ADLs/Adaptive

As it takes time to evaluate a child for a wheelchair, get insurance approval, and order the wheelchair, possibly as long as 6 months, this needs to be done before the girl with RS is having great difficulty walking. Parents generally find that having a wheelchair available is helpful although sometimes initially raising the issue of a child needing a wheelchair can be emotionally difficult. Good positioning in a wheelchair with postural support and availability of a tray for toys and food may be helpful for preventing scoliosis and developmental tasks.

Girls with RS will usually need developmental and rehabilitative therapies including PT, OT, and speech, and may benefit from an augmentative communication device. See Augmentative Communication (general).

Mental Health/Behavior

Agitation, self-injurious behavior, and other behavior abnormalities are frequent in girls with RS, and behavior problems can be overwhelming for families. Behavioral counseling and medications may be necessary to manage these problems, especially agitation. Before visiting professionals for help, families should keep a brief record of the problem behaviors and their frequency as well as factors that bring on the behavior or decrease it. Low-dose resperidone, other atypical antipsychotics, and SSRIs have been used to treat agitation when necessary. Naltrexone may also be helpful for self-injurious behavior. See [Peebles: 2012] for a theoretical explanation of why self-injurious behavior occurs in individuals with intellectual disability.

Subspecialist Collaborations & Other Resources

Psychiatrist, Child-18 (see Services below for relevant providers)

For medical management of behavior problems.

Respiratory

Abnormal breathing in RS does not normally need treatment; although episodes of abnormal breathing may appear dangerous, they usually consist of hyperventilation followed by normal breathing. Topiramate, which is prescribed for girls with RS for seizures, may also help with breathing problem. [Goyal: 2004] Naltrexone, an opiate antagonist, may help control irregular breathing, and may be helpful in decreasing agitation and self-injurious behavior.

Subspecialist Collaborations & Other Resources

Pediatric Pulmonology (see Services below for relevant providers)

In some cases of very frequent abnormal breathing patterns, a visit with a pediatric pulmonologist may be helpful.

Sleep

Sleep problems are common and difficult in girls with Rett syndrome, and should be treated if they are causing disruption to the family. Sleep problems may be noted as early as a few months of age. Medical problems disrupting sleep, e.g., reflux, and seizures need to be ruled out, and treatment should begin with behavioral interventions. If not successful, medications that might be helpful include diphenhydramine, chloral hydrate (successful only for short periods), melatonin, low-dose trazadone and clonidine. See Medications for Sleep (general) for more information. See [Carotenuto: 2013] for a description of polysomnography in Rett syndrome.

Subspecialist Collaborations & Other Resources

Pediatric Sleep Medicine (see Services below for relevant providers)

Management consultation by a sleep specialist may be helpful.

Maturation/Sexual/Reproductive

There is not much information on sexual development in girls with RS, but in 1 study girls achieved maturation at typical ages despite growth retardation. [Holm: 1986] Menstrual periods may be difficult to manage in girls with difficulty using their hands and intellectual disability. Various treatments are available including depo-provera, non-cycling oral contraceptives, and intrauterine devices (IUDs). For more information, see Sexuality and People with Disabilities (PDF Document 257 KB).

Subspecialist Collaborations & Other Resources

Gynecology (Ped/Adol, Special Needs) (see Services below for relevant providers)

Providers on this list have indicated they are comfortable providing gynecologic care for girls with special needs.

Frequently Asked Questions

What is my child's life expectancy?

Most girls with RS live normal lifespans, although there is a small percentage who die unexpectedly of unknown causes. In one recent study in China, girls with RS had a 100% survival rate at 10 years of age and 87.5% at 25 years of age. [Wong: 2007] Etiologies that have been implicated include heart rhythm abnormalities and seizures; there does not appear to be any single cause however. [Kerr: 1999] The IRSA has recommended yearly EKG screening for heart rhythm abnormalities and seizures, if present or suspected, should be discussed with your Medical Home provider.

Issues Related to Rett Syndrome

Development (general)

Augmentative Communication

Funding & Access to Care

Writing Letters of Medical Necessity

Gastro-Intestinal & Bowel Function

Gastroesophageal Reflux

Resources

Information for Clinicians

MECP2-Related Disorders (GeneReviews)
An expert-authored, peer-reviewed, current disease description that applies genetic testing to diagnosis and management information; sponsored by the U.S. National Center for Biotechnology Information, U.S. National Library of Medicine.

Helpful Articles

PubMed search for Rett syndrome in children, last 3 years

Castro J, Mellios N, Sur M.
Mechanisms and therapeutic challenges in autism spectrum disorders: insights from Rett syndrome.
Curr Opin Neurol. 2013;26(2):154-9. PubMed abstract

Lotan M, Zysman L.
The digestive system and nutritional considerations for individuals with Rett syndrome.
ScientificWorldJournal. 2006;6:1737-49. PubMed abstract

Nomura Y, Segawa M.
Natural history of Rett syndrome.
J Child Neurol. 2005;20(9):764-8. PubMed abstract

Segawa M, Nomura Y.
Rett syndrome.
Curr Opin Neurol. 2005;18(2):97-104. PubMed abstract

Venkat A, Jauch E, Russell WS, Crist CR, Farrell R.
Care of the patient with an autism spectrum disorder by the general physician.
Postgrad Med J. 2012;88(1042):472-81. PubMed abstract

Clinical Tools

Assessment Tools/Scales

Constipation Evaluation Tool (PDF Document 84 KB)
Provides a format for evaluation of chronic constipation in children.

Home Toileting Record (PDF Document 49 KB)
An easy-to-use form for keeping track of a child's toileting habits.

Information & Support for Families

Family Diagnosis Page

Information on the Web

International Rett Syndrome Association (IRSA)
This link contains information about RS, research, ongoing studies, and RS related news.

El Síndrome de Rett
Spanish language overview of Rett syndrome with links to other organizations, from the National Institute of Neurlogical Disorders and Stroke.

Rett Syndrome (Genetics Home Reference)
Excellent, detailed review of condition for patients and families; sponsored by the U.S. National Library of Medicine.

Rett syndrome (MedlinePlus)
brief description of RS and numerous links to other reliable sources of information for parents and family members; from the National Library of Medicine.

Support National & Local

International Rett Syndrome Association (IRSA)
This link contains information about RS, research, ongoing studies, and RS related news.

Studies/Registries

Specific therapeutics are now in clinical trials. See [Castro: 2013]

Rett syndrome clinical trials
This NIH website lists current open clinical trials for girls with Rett syndrome.

Services for Patients & Families

Adaptive Recreation

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After School Programs

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Art Therapy

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Assistive Technology

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Behavioral Programs

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Bone Densitometry/DEXA

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Childcare, Special Needs

See all Childcare, Special Needs services providers (2) in our database.

Developmental - Behavioral Pediatrics

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Developmental Pediatrics

See all Developmental Pediatrics services providers (22) in our database.

Estate & Future Planning

See all Estate & Future Planning services providers (1) in our database.

General Pediatric Surgery

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Gynecology (Ped/Adol, Special Needs)

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Local Support Groups, Child Abuse

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National Support Groups, Disab/Diag

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Nutrition/Dietary

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Pediatric Cardiology

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Pediatric Endocrinology

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Pediatric Gastroenterology

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Pediatric Genetic Counseling

See all Pediatric Genetic Counseling services providers (1) in our database.

Pediatric Genetics

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Pediatric Neurology

See all Pediatric Neurology services providers (22) in our database.

Pediatric Orthopedics

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Pediatric Physical Medicine & Rehab

See all Pediatric Physical Medicine & Rehab services providers (2) in our database.

Pediatric Pulmonology

See all Pediatric Pulmonology services providers (6) in our database.

Pediatric Sleep Medicine

See all Pediatric Sleep Medicine services providers (1) in our database.

Psychiatrist, Child-18

See all Psychiatrist, Child-18 services providers (116) in our database.

Respite Care

See all Respite Care services providers (5) in our database.

Schools for Children with Autism

See all Schools for Children with Autism services providers (2) in our database.

Services for People with Disabilities

See all Services for People with Disabilities services providers (1) in our database.

Swallow Studies

We currently have no Swallow Studies service providers listed; search our Services database for related services.

For other services related to this condition, browse our Services categories or search our database.

Authors

Authors: Karin Dent, MS, CGC - 6/2013
Lynne M Kerr, MD, PhD - 6/2013
Content Last Updated: 10/2015

Bibliography

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Polysomnographic findings in Rett syndrome: a case-control study.
Sleep Breath. 2013;17(1):93-8. PubMed abstract

Castro J, Mellios N, Sur M.
Mechanisms and therapeutic challenges in autism spectrum disorders: insights from Rett syndrome.
Curr Opin Neurol. 2013;26(2):154-9. PubMed abstract

Dolce A, Ben-Zeev B, Naidu S, Kossoff EH.
Rett syndrome and epilepsy: an update for child neurologists.
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Is the early development of girls with Rett disorder really normal?.
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Abnormal general movements in girls with Rett disorder: the first four months of life.
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Effect of topiramate on seizures and respiratory dysrhythmia in Rett syndrome.
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An update on clinically applicable diagnostic criteria in Rett syndrome. Comments to Rett Syndrome Clinical Criteria Consensus Panel Satellite to European Paediatric Neurology Society Meeting, Baden Baden, Germany, 11 September 2001.
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Bisphosphonates to treat osteopenia in children with quadriplegic cerebral palsy: a randomized, placebo-controlled clinical trial.
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Physical growth and development in patients with Rett syndrome.
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Recent insights into hyperventilation from the study of Rett syndrome.
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Kerr AM, Webb P, Prescott RJ, Milne Y.
Results of surgery for scoliosis in Rett syndrome.
J Child Neurol. 2003;18(10):703-8. PubMed abstract

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Rett syndrome in Australia: a review of the epidemiology.
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Lotan M, Zysman L.
The digestive system and nutritional considerations for individuals with Rett syndrome.
ScientificWorldJournal. 2006;6:1737-49. PubMed abstract

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Clinical genetic evaluation of the child with mental retardation or developmental delays.
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Motil KJ, Barrish JO, Lane J, Geerts SP, Annese F, McNair L, Percy AK, Skinner SA, Neul JL, Glaze DG.
Vitamin D deficiency is prevalent in girls and women with Rett syndrome.
J Pediatr Gastroenterol Nutr. 2011;53(5):569-74. PubMed abstract

Motil KJ, Caeg E, Barrish JO, Geerts S, Lane JB, Percy AK, Annese F, McNair L, Skinner SA, Lee HS, Neul JL, Glaze DG.
Gastrointestinal and nutritional problems occur frequently throughout life in girls and women with Rett syndrome.
J Pediatr Gastroenterol Nutr. 2012;55(3):292-8. PubMed abstract / Full Text

Nomura Y, Segawa M.
Natural history of Rett syndrome.
J Child Neurol. 2005;20(9):764-8. PubMed abstract

Peebles KA, Price TJ.
Self-injurious behaviour in intellectual disability syndromes: evidence for aberrant pain signalling as a contributing factor.
J Intellect Disabil Res. 2012;56(5):441-52. PubMed abstract / Full Text

Scala E, Ariani F, Mari F, Caselli R, Pescucci C, Longo I, Meloni I, Giachino D, Bruttini M, Hayek G, Zappella M, Renieri A.
CDKL5/STK9 is mutated in Rett syndrome variant with infantile spasms.
J Med Genet. 2005;42(2):103-7. PubMed abstract / Full Text

Segawa M, Nomura Y.
Rett syndrome.
Curr Opin Neurol. 2005;18(2):97-104. PubMed abstract

Venkat A, Jauch E, Russell WS, Crist CR, Farrell R.
Care of the patient with an autism spectrum disorder by the general physician.
Postgrad Med J. 2012;88(1042):472-81. PubMed abstract

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Preventive Management of Children with Congenital Anomalies and Syndromes.
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Rett syndrome: prevalence among Chinese and a comparison of MECP2 mutations of classic Rett syndrome with other neurodevelopmental disorders.
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