RETT SYNDROME

ArunrajGroup-10Tbilisi state medical university

Overview Rett syndrome is a rare, but severe brain disorder

that affects girls.  It is related to various mutations on

the MECP2 gene, which codes for methyl-CpG binding protein-2 (MECP2).

MECP2 is expressed in neurons and glial cells. Rett Syndrome is estimated to affect 1 in every

10,000 to 15,000 live female births in all racial and ethnic groups worldwide.

Diagnosis is based on clinical observation of signs and symptoms during the child's early growth and development.

Treatment involves a multidisciplinary approach that focuses on the management of symptoms.

ETIOLOGY Usually Rett syndrome is caused by a mutation

in the methyl CpG binding protein 2 ( MECP2 ) gene. The MECP2 gene is involved in the production of a protein called methyl-cystine binding protein 2 ( MeCP2) which is needed for brain development and acts as a biochemical switch that can either increase gene expression or tell other genes when to turn off and stop producing their own unique proteins. The MECP2 gene does not function normally in Rett syndrome so that structural abnormal forms or inadequate amounts of the protein are produced and can cause other genes to have abnormal gene expression.

The development of Rett syndrome (RS) progresses through 4 stages, which are typically reached at the following ages:

•Stage I - Developmental arrest (6-18 months)•Stage II - Rapid deterioration or regression (1-4 years) •Stage III - Pseudostationary (2-10 years)•Stage IV - Late motor deterioration (>10 years)

Clinical features

•Stage I - Gross motor development delay; loss of eye contact; deceleration of head, weight, and height growth; hypotonia; hand wringing; abnormal placidity and calmness; no cutaneous findings on Wood lamp examination.

•Stage II - Autisticlike behavior; midline hand wringing, clapping, hand washing, or hand-to-mouth movements; episodes of hyperventilation or breath-holding; seizures and vacant spells that resemble seizures; intermittent strabismus and irritability

•Stage III - Hand stereotypies, rigidity, hyperventilation, breath holding, bruxism, involuntary tongue movements, poor weight gain, and scoliosis.

•Stage IV - Dystonia, rigidity, muscle wasting, quadriparesis, scoliosis or kyphoscoliosis, loss of ambulation, growth retardation, hyperventilation, and seizures; improved frequency and intensity of hand movements; preserved eye contact.

DIAGNOSISClinical & Genetic testingDiagnosis is made clinically by observing signs and symptoms during the child’s early growth and development. Ongoing evaluation of the child’s physical and neurologic status is needed.

Genetic testing for the MECP2 mutation on the X chromosome (Xq28) is used to complement the clinical diagnosis.

TREATMENT Medications

Medications can be taken to help with the symptoms like seizures and muscle stiffness, but can't be taken to cure the disease Bromocriptine: test trials with Rett syndrome patients have

been used to improve relaxation and communication skills Dextromethorphan: being used to determine if DM will

prevent the harmful over-stimulation of the neurons thereby reducing EEG spike activity and aims to find out which dose if any will help improve EEG abnormalities, behavior, cognition, and reduce seizures, as well as improve breathing abnormalities, motor capabilities, bone density, and GI dysfunction.

Folate and betaine L- carnitine: which may help improve language skills,

muscle mass, alertness, energy and quality of life while decreasing constipation and daytime sleepiness

L-dopa: for motor rigidity in later stages of the disease

Prognosis Survival rates decline in individuals older

than 10 years; the 35-year survival rate is 70%. Death may be sudden and often is secondary to pneumonia. Risk factors include seizures, loss of mobility, and difficulties with swallowing. The life expectancy is more favorable in patients with RS than in other individuals with profound intellectual disability, which is associated with a 35-year survival rate of only 27%.

Developmental potential for patients with RS is difficult to predict.