Retts syndrome(1)

Rett syndrome is a neurodevelopmental disorder that affects girls almost exclusively.
It is characterized by normal early growth and development followed by a slowing of development, loss of purposeful use of the hands, distinctive hand movements, slowed brain and head growth, problems with walking, seizures, and intellectual disability.

1. Presentation on Rett Syndrome Dr. P. Asma Afreen

2. INTRODUCTION: Rett syndrome is a neurodevelopmental disorder that affects girls almost exclusively. It is characterized by normal early growth and development followed by a slowing of development, loss of purposeful use of the hands, distinctive hand movements, slowed brain and head growth, problems with walking, seizures, and intellectual disability.

3. The rett’s disease was first founded by Dr. Andreas Rett . An Austrian Physician who first described it in a article in 1966.

4. EPIDERMIOLOGY 99.5% of rett syndrome occurs only once in a family Life span average is more than 50 years Require care and assistance through lifetime

5. AETIOLOGY Most children with Rett syndrome have a mutation on the X chromosome. Exactly what this gene does, or how its mutation leads to Rett syndrome, isn’t clear. Researchers believe that the single gene may influence many other genes involved in development. Although Rett syndrome is genetic, children almost never inherit the faulty gene from their parents. Rather, it’s a chance mutation that happens in DNA. When boys develop the Rett syndrome mutation, they rarely live past birth. Males have only one X chromosome (instead of the two girls have), so the effects of the disease are much more serious, and almost always fatal.

6. STAGES Rett syndrome is commonly divided into four stages: Stage I: early onset.  Signs and symptoms are subtle and easily overlooked during the first stage, which starts between 6 and 18 months of age and can last for a few months or a year. Babies in this stage may show less eye contact and start to lose interest in toys. They may also have delays in sitting or crawling. Stage II: rapid deterioration.  Starting between 1 and 4 years of age, children lose the ability to perform skills they previously had. This loss can be rapid or more gradual, occurring over weeks or months.

7. Symptoms of Rett syndrome occur, such as slowed head growth, abnormal hand movements, hyperventilating, screaming or crying for no apparent reason, problems with movement and coordination, and a loss of social interaction and communication. Stage III: plateau.  The third stage usually begins between the ages of 2 and 10 years and can last for many years. Although problems with movement continue, behavior may have limited improvement, with less crying and irritability, and some improvement in hand use and communication. Seizures may begin in this stage and generally don't occur before the age of 2.

8. Stage IV: late motor deterioration.  This stage usually begins after the age of 10 and can last for years or decades. It's marked by reduced mobility, muscle weakness, joint contractures and scoliosis. Understanding, communication and hand skills generally remain stable or improve slightly, and seizures may occur less often.

9. SYMPTOMS Stage I - Gross motor development delay, disinterest in play, and loss of eye contact; hypotonia ; hand wringing; unusual placidity and calmness; vague and nonspecific early symptoms; breath-holding spells Stage II - Deterioration; autisticlike behavior; stereotypic hand movements during wakefulness; breathing irregularities; seizures and vacant spells that resemble seizures; sleep disorders, intermittent strabismus, and irritability

10. Stage III - some improvement in behavior, hand use, Communication skills : good eye contact and attempts Communicate intent : continued mental impairment Hand stereotypies:increasing rigidity Involuntary tongue movements Motor dysfunction and seizures Continued breathing irregularities Poor weight gain despite good appetite Difficult feeding and some degree of oral motor dysfunction

11. Stage IV - No additional deterioration of cognitive skills, communication skills, or hand skills Increased motor problems Cessation of walking Possible reduction of seizure frequency

12. Pathophysiology: MECP2 gene located on X chromosome Loss of protein function and un regulated expressions Effects on nervous system Initial stages MECP2 It act as transcriptional repressor or activator 70% of RS cases due to missense mutation and 4 non sense proteins truncating mutations Sporadic cause gene destruction resulting greater severity MECP2

13. COMPLICATIONS Sleep problems that cause significant sleep disruption to the person with Rett syndrome and family members Difficulty eating, leading to poor nutrition and delayed growth Bowel and bladder problems, such as constipation, gastroesophageal reflux disease (GERD), bowel or urinary incontinence, and gallbladder disease Muscle , bone and joint problems Anxiety and problem behavior that may hinder social functioning

14. DIAGNOSIS Genetic testing:- A genetic test can identify the gene mutation on the X chromosome. Neuroimaging ( MRI) Electroencephalography (EEG) Polygraphic respiratory recordings Psychometric testing

15. Neurophysiologic testing (auditory brainstem-evoked responses, somatosensory -evoked responses. Electroretinography (ERG)

16. Non Pharmacologial Treatment There’s no cure for rett syndrome, so treatment focuses on managing the symptoms. Child may benefit from some of the following treatments and aids: Speech and language therapy, picture boards, eye gaze technology and other visual aids to help with communication. Medication for breathing and mobility problems, and anti-epileptic medicine to control seizures. Physiotherapy, attention to mobility, careful attention to child’s sitting posture and frequent changes in posture. If scoliosis does become established, a back brace and sometimes spinal surgery may be used to prevent the spine curving further.

17. PHARMACOLOGICAL TREATMENT Although there is no cure for Rett syndrome, treatments are directed toward symptoms and providing support, which may improve the potential for movement, communication and social participation. : Regular medical care.  Management of symptoms and health problems may require a multispecialty team. Regular monitoring of physical changes such as scoliosis and GI and heart problems is needed. Medications.  Though medications can't cure Rett syndrome, they may help control some signs and symptoms associated with the disorder, such as seizures, muscle stiffness.

18. Problems with breathing, sleep, the gastrointestinal tract . Physical therapy.  Physical therapy and the use of braces or casts can help children who have scoliosis or require hand or joint support. In some cases, physical therapy can also help maintain movement, create a proper sitting position, and improve walking skills, balance and flexibility Occupational therapy.  Occupational therapy may improve purposeful use of the hands for activities such as dressing and feeding.

19. Speech-language therapy.  Speech-language therapy can help improve a child's life by teaching nonverbal ways of communicating and helping with social interaction.And for improved mental, physical and social abilities. A high-calorie, well-balanced diet may be recommended. Behavioral intervention.  Practicing and developing good sleep. Nutritional support.  Proper nutrition is extremely important for normal growth p habits may be helpful for sleep disturbances.

20. PREVENTION Presently , Rett syndrome cannot be prevented. In most cases, the genetic mutation that is responsible for the disorder occurs randomly and spontaneously. However, couples who already have a child with Rett syndrome or have another family member who is affected may choose to discuss genetic testing with doctor. In a family who has had a child with Rett syndrome, the probability of having another child with Rett syndrome is very low but mothers should undergo carrier testing since recurrence risk is 50% if the mother is found to be a carrier.

21. REFERENCE: https://www.mayoclinic.org/diseases-conditions/rett-syndrome/symptoms-causes/syc-20377227 https://emedicine.medscape.com/article/916377-overview#a4 https://www.slideshare.net/kylemiyahara/rett-syndrome https://www.medicinenet.com/script/main/art.asp?articlekey=11960 https://www.mayoclinic.org/diseases-conditions/rett-syndrome/diagnosis-treatment/drc-20377233

22. Thank you