Rett Syndrome

Annika Jones

Daniel Osborne

Amanda Roth

Eric Aldea

Definition

• Rett syndrome is an incurable, rare, genetic disorder which affects the development of the brain. It occurs mainly in girls and is most often be misdiagnosed as autism or cerebral palsy. The onset of the symptoms of Rett Syndrome appear after a normal period of growth and development. Rett syndrome causes problems with a child's motor skills, affecting the use of their hands, walking, eating, and breathing.

Causes

• The majority of the cases are caused by mutation of the MECP2 gene which in involved in producing a protein that is essential for brain development. The gene appears on the x chromosome

– Only a few cases reported to be inherited – Usually, the mutation happens randomly– Affects about 1 in 10,000 births

Causes

• Boys– Rett Syndrome in boys: Because boys have one

x chromosome and one y chromosome, the x chromosome can't be inactivated. Therefore, boys can't be protected from the severe effects of the disease. They usually die at birth or a few months afterward

Causes

• Girls – Rett syndrome in girls: Because girls

have two x chromosomes and a cell only needs one copy of the gene that works, each cell inactivates one of its chromosomes . The more cells that have the gene inactivated, the less severe the symptoms

– http://www.youtube.com/watch?v=o0n8ym2KXRM

Symptoms

• While the symptoms vary from child to child, there are 4 general stages to Rett syndrome:

• 6-18 months: – The symptoms are easily overlooked, with most babies developing normally. If abnormal signs are

being displayed, they usually consist of a delay in sitting or crawling and don't demonstrate eye contact

• 1-4 years old: – Begin to lose the ability to speak – Chorea (spasmodic movements of hand or facial muscles)– They may also breath abnormally – Crying and Screaming without provocation – Microcephaly (Abnormally small heads)

Symptoms cont.

• 2-10 years old: – problems with mobility continue, (however, behavior

begins to improve) which include:– less crying,– become more alert, – improved attention span – non verbal communication skills

This is the plateau stage, and many who are afflicted with Rett syndrome stage in this stage for the rest of their lives

• Ages varied: – Scoliosis (an abnormal curvature of the spine)– Hypotonia (weakness of the muscles) – decreased mobility– Bruxism ( Grinding of the Teeth)

Symptoms cont.

• Ages Varied cont. – Ataxia (Involuntary movements) – Epileptic Seizures

• http://www.youtube.com/watch?v=H2vH1igOoh0

– Dystonia ( Repetitive movements) • http://en.wikipedia.org/wiki/File:Hemichorea_a

nd_dystonia.ogv

• Most people with Rett syndrome live to be between 40-50 and need continuous care throughout their life

Diagnosing Rett Syndrome

• Genetic testing• Clinical diagnosis- looking for abnormal signs and behaviors• Looking for a period of normal growth and then a gradual

regression of development• muscular atrophy• EEG abnormalities • epileptic seizures • scoliosis • repetitive hand movements • breathing abnormalities

Treatment Options

• Physical, occupational and speech therapy – Physical therapy: can be used for scoliosis, help maintain

walking abilities, balance and flexibility– Occupational therapy: may help with purposeful use of hands– Speech therapy: can teach non-verbal communication

• Nutrition is extremely important for growth and development; some may respond to high fat, high calorie diet while others may need to be fed through a tube in the nose or directly through the stomach

• Alternative medicine: massage therapy, acupuncture, chiropractic therapy

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

Research

• The MECP2 gene was discovered in 1999– Research is being conducted on how the MECP2 protein

works in order to manipulate other chemical pathways to make up for the malfunctioning MECP2, helping to prevent any further progression of the disease.

• Other genes, FOXG1 and CDKL5, have been identified as other genes that may also effect the development of Rett syndrome

Research

• FOXG1: specific function has not yet been determined; however, it may help in brain and telencephalon (cerebrum) development

• -CDKL5: essential in normal brain development; acts as a kinase, an enzyme that alters the activity of other proteins by adding oxygen and phosphate atoms at different positions. Researchers have not found what proteins are effected by CDKL5. The mutation of the gene changes a single amino acid that is integral for its kinase function. The effect of the mutation of CDKL5 in Rett syndrome is related to it working in conjunction with MECP2

Work Cited

• http://www.mayoclinic.com/health/rett-syndrome/DS00716• http://en.wikipedia.org/wiki/FOXG1• http://www.cdkl5.com/• http://www.rettsyndrome.org/index.php?option=com_content&task=

blogsection&id=6&Itemid=944• http://www.umm.edu/ency/article/001536.htm• http://www.ncbi.nlm.nih.gov/pubmed/2360701?ordinalpos=1&itool=E

ntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=1&log$=relatedarticles&logdbfrom=pubmed

• http://clinicaltrials.gov/ct2/show/NCT00593957• http://www.rettsyndrome.org.uk/Diagnosing_RS.htm• http://www.ninds.nih.gov/disorders/rett/detail_rett.htm#118393277• http://en.wikipedia.org/wiki/Rett_syndrome#Development_and_sym

ptoms