The development of Rett syndrome happens in 4 stages . The ages at which each stage occurs and the presentations for the stage are detailed below:
This is known as developmental arrest and is seen in patients aged 6-18 month. Symptoms include:
- Delay in gross motor development
- Lack of interest in playing
- Inability to maintain eye contact
- Wringing of the hands (the main sign of the disease)
- Calm and dull appearance that is not seen in healthy infants of same age
- Hyperventilation and holding of breath
This is the rapid deterioration or regression stage and it is seen in children aged 1-4 years.
- Behaviour consistent with autism is most dominant at this stage and so the child loses ability to speak and is unable to use the finger and hands naturally.
- During wakefulness, hand-to-mouth movements, clapping, wringing etc. are noticeable.
This is the pseudostationary stage and is seen in children aged 2-10 years.
- Feeding is often difficult at this stage.
- Rigidity and involuntary movement of the tongue is also common.
This is the Late motor deterioration stage and it is seen in children aged 10 years and above (>10 years).
Entire Body System
- Short Stature
A striking deceleration of growth has been found across all measurements in most girls with Rett syndrome who end up with short stature and microcephaly. The mortality (death) rate among children with Rett syndrome is increased (1.2% per year). [medicinenet.com]
Rett syndrome patients with short stature, females (000s) Table 10. Rett syndrome patients with skeletal problems, females (000s) Table 11. Rett syndrome patients with seizures, females (000s) Table 12. [giikorea.co.kr]
Short stature, renal dysfunction, and polydactyly are some signs of Bardet-Biedl syndrome or Laurence-Moon syndrome when associated with pigmentary retinopathy. [patient.info]
Upon its binding to methylated/hydroxymethylated DNA, MeCP2 is able to recruit a plethora of interacting protein and RNA partners. [ncbi.nlm.nih.gov]
Face, Head & Neck
Mutations in the P/Q type calcium channel CACNA1A have been implicated in epileptic encephalopathy, familial hemiplegic migraine, episodic ataxia 2, and spinocerebellar ataxia 6, but not Rett syndrome. [ncbi.nlm.nih.gov]
Cerebroatrophic hyperammonemia, dementia, ataxia, and loss of purposeful hand use, Rett disorder, Rett's disorder, Rett's syndrome, RTT, RTS Prevention - Rett syndrome There's no known way to prevent Rett syndrome. [checkorphan.org]
The affected female is normal until the age of 6-25 months when progressive loss of voluntary control of hand movements and communication skills; ataxia; seizures; autistic behavior; intermittent hyperventilation; and hyperammonemia appear. [icd10data.com]
- Abnormal Gait
Rett syndrome is a neurodevelopmental genetic disorder, characterized by developmental delay, hand stereotypies, abnormal gait, and acquired microcephaly. Epilepsy is very common in Rett syndrome and can be medically intractable. [ncbi.nlm.nih.gov]
[…] breathing difficulty ambulating seizures Physical exam apraxia abnormal gait scoliosis decreased head circumference usually starts to become evident at 5-6 months poor circulation indicated by cold, blue extremities Imaging Radiographs recommended views [orthobullets.com]
These gait patterns are among the most common gait abnormalities in children with cerebral palsy. [en.wikipedia.org]
- Neurologic Manifestation
Neuroimaging may be used to exclude other causes of the neurological manifestations. ECG and possibly 24-hour ECG may be needed, as there is an association with cardiac arrhythmias. [patient.info]
- Rotary Nystagmus
He has a prominent rotary nystagmus, which has attenuated with age, and striking bilateral pupillary constriction (miosis). He has periodic breathing while awake and asleep. [doi.org]
- Axial Dystonia
He presented the association of postnatal microcephaly, severe axial dystonia with severe feeding difficulties with protruding tongue movements during the first year of life that subsequently evolved into dyskinetic movement disorders with hand stereotypies [ncbi.nlm.nih.gov]
Females that present any of the clinical presentations above are subjected to genetic testing to properly establish the presence of the condition   . In patients where MECP2 mutation is not found, it is important to undergo other diagnostic tests that are aimed at finding out the possible causes of the signs and symptoms being experienced.
At present, there is no cure for the Rett syndrome. However, studies have demonstrated that restoration of the functions of the MECP2 may bring about a cure . The treatment of the condition focuses on management. This includes the following:
- Management of gastrointestinal issues like reflux and constipation and nutritional poor weight gain issues
- Surveillance of scoliosis
- Surveillance of long QT syndrome by annual ECG
- Increasing the patient's communication skills, especially with augmentative communication strategies
- Parental counselling
- Modifying social medications
- Provision of sleep aids
It is not easy to predict the developmental potential for patients with the Rett syndrome. Some individuals with this syndrome are able to maintain and achieve some functional skills . Around 60% of RS patients are able to retain their abilities to ambulate. Others lose ambulation and due to scoliosis, dystonia, or atrophy, they may never walk.
The survival rate is poor in individuals that are 10 years or older and the 35-year survival rate is placed at 70%. Death may be sudden and is often followed by secondary pneumonia. Some of the risk factors commonly seen are difficulty with swallowing, loss of mobility and seizures. It is however, important to note that life expectancy is better in patients with Rett syndrome in comparison to patients with profound intellectual disability. The 35-year survival rate for the latter is only 27%.
Rett syndrome is caused genetically by mutations that occur in the MECP2 gene that is found on the X chromosome . It can arise sporadically or from germline mutations. Rett syndrome was first described via clinical observations but the diagnosis becomes definitive only when the defect in the MECP2 gene becomes definitive. However, there have been some rare cases of the condition where the MECP2 remains unaffected.
Approximately, the incidence of Rett syndrome occurs is 1 case per 23,000 live female births. In some countries, wide variations have been reported with some of them posting figures showing 1 case per 10,000 live female births . Figures in Japan suggest 1 case per 45,000 females aged 6 to 14. Variations in incidence may be due to the inclusion of atypical and/or variant forms of this condition. The atypical forms include congenital RS, preserved speech variants, as well as milder forms with later onset of regression.
The syndrome becomes evident clinically by 2 to 4 years of age, however the neurodevelopmental malfunction in children begin when they are 6 to 18 months or younger.
The patients identified are often female because the disease is X-linked. Most of the males that have the syndrome are believed to die in utero.
Studies have shown no racial variations of the syndrome as well.
The severity and symptom of the RS condition is dependent on both the percentage of defective genes that are activated as well as the type of mutation responsible for the condition . Varying mutation types have been seen in the 3 coding regions of the MECP2 gene and most of these cause truncations and missense proteins.
The mutations in the MECP2 gene bring about a loss of function of this protein with an unregulated expression of the genes that are normally affected. Some of these are crucial in the development of the nervous system past the early stages. The nervous system is the primary site of the condition but the specific target genes remain unknown. Due to the dysfunction of the MECP2 gene, astrocyte function is abnormal in Rett syndrome patients.
Rett syndrome cannot be prevented.
Formerly known as cerebroatrophic hyperammonemia, Rett syndrome (RS) is a genetic and neurologic disorder that affects the grey matter of the brain . It is a very rare condition that is seen predominantly in females with occasional occurrence in males.
The common clinical features are deceleration in head growth and small hands and feet. Other common symptoms are repetitive hand movements such as continuously putting hand in mouth and hand wringing. Growth failure, scoliosis and constipation are also common and they prove the most problematic amongst all symptoms. Individuals with this condition are prone to gastrointestinal disorders and as much as 80% of affected people have seizures. They generally do not have any verbal skills and more than 50% of those affected do not walk.
Rett syndrome is a genetic disorder that has been classified as rare. It affects the way the brain develops and is seen almost entirely in girls.
Babies that have this condition develop normally at first but the symptoms become visible by the time they are 6 months old. As time passes, children with the condition show increasing difficulty with movement, communication and coordination. This often affects their ability to use their hands, walk and communicate.
Presently, there is no known cure for the condition but potential treatments are being considered. Treat for now is focused on improving movement and communication and also providing care and support for the affected children and their families.
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- Cheadle JP, Gill H, Fleming N, et al. Long-read sequence analysis of the MECP2 gene in Rett syndrome patients: correlation of disease severity with mutation type and location. Hum Mol Genet 2000; 9:1119.