Rett Syndrome

1
Rett Syndrome

• Alisha Byus Renee Devlin Anne
  Hoffman Andrea Ruwe

2
History and Origin

• Named for Dr. Andreas Rett, organized in 1983
• Vienna, Austria
• Pediatrics and Neurology
• Observed 2 girls in waiting room with similar
  hand movements in 1960
• Initial symptoms indicate what neurons are
  affected in the brain
• First published article (Hasberg et al.) with
  additional cases in 1983

www.rettsyndrome.org
3
Pervasive Developmental Disorders

• Autistic Disorder
• Asperger Disorder
• Childhood Disintegrative Disorder
• Rett Syndrome
• Pervasive Developmental Disorder - Not Otherwise
  Specified (PDD-NOS)

Diagnostic Statistic Manual-4th Edition (1994)
(DSM-IV)
? As more is learned about Rett Syndrome, it
is likely that the diagnostic criteria will soon
be revised, and Rett syndrome will not be
categorized with other pervasive developmental
disorders. The characteristics of a child with
Rett Syndrome are no longer congruent with those
of a child with Autism.
Dr. Ratlif-Schaubb (2008) Nationwide Childrens
Hospital
4
Etiology

• The majority of cases of Rett syndrome are caused
  by nonhereditary, acquired changes or mutations
  in the Rett syndrome gene on the X chromosome.
• Males with this defect often die before birth or
  in infancy
• Males that live through infancy have an extra
  X-chromosome in many/all of the bodys cells
• Klinefelter syndrome

5
Etiology

• Mutations in the CDKL5 and MECP2 genes cause Rett
  syndrome
• Majority of classic on the MECP2 gene (75)
• This gene provides direction for typical brain
  development.
• Connects synapses to nerve fibers
• Mutations in CDKL5
• Atypical form of Rett syndrome
• Early onset seizure variant

6
Etiology Inheritance

• 99 with classic Rett syndrome have no family
  history
• Inheritance research has shown
• X-linked
• Dominant
• Groups with diseases in families more prevalent
  in
• Norway, Sweden, Northern Italy
• Genetics tests are used but cannot identify every
  patient

7
Risk Factors

• There are no known risk factors with the
  exception of being female
• Mutation is sporadic
• Chance of having a second child with Rett
  Syndrome is less than 1
• No opportunities for prevention

8
Other CommonMedical Issues

• Scoliosis
• 80 of girls with Rett Syndrome
• Constipation and gastro-esophageal reflux
• Cardiac problems
• Feeding, swallowing, chewing
• Unusual breathing pattern (non-apneaic)
• Sleep disruption
• Including sudden death in sleep
• Seizures
• Very little is known of the life expectancy
• Very few women in 40s/50s with diagnosis

9
Epidemiology

• Data are limited to case studies
• This disorder has been reported mainly in
  females
• Prevalence rate of Rett Syndrome
• 1 in 10,000 1 in 15,000

10
Epidemiology

• Rett Syndrome Course
• Rett Syndrome has its onset prior to age 4 years,
  usually in the first or second year of life.
• The duration of the disorder is lifelong, and the
  loss of skills is generally persistent and
  progressive.
• In most instances, recovery is quite limited,
  although some very modest developmental gains may
  be made and interest in social interaction may be
  observed as individuals enter later childhood or
  adolescence.
• This disorder follows a continuous course. The
  social, communicative, and behavioral
  difficulties remain relatively constant
  throughout life.

11
Diagnostic Features

• Essential features of Rett Syndrome
• Development of multiple specific deficits
  following a period of normal functioning after
  birth
• Apparently normal prenatal and perinatal period
  with normal psychomotor development through the
  first 5 months of life
• Head circumference at birth is also within normal
  limits

12
Epidemiology Associated Features

• Typically associated with Severe or Profound
  Mental Retardation
• Increased frequency of EEG abnormalities and
  seizure disorder
• Nonspecific abnormalities on brain imaging have
  been reported

13
Differential Diagnosis

• Rett syndrome is often mistaken for autism,
  cerebral palsy, and mental retardation
• Rett syndrome differs from Childhood
• Disintegrative Disorder, Autistic Disorder
• Asperger Syndrome in the following areas
• Sex ratio
• 2. Onset
• 3. Pattern of deficits

14
Diagnostic criteria for Rett Syndrome (DSM-IV)

• A. All of the following
• apparently normal prenatal and perinatal
  development
• apparently normal psychomotor development through
  the first 5 months after birth
• normal head circumference at birth
• B. Onset of all of the following after the period
  of normal development
• deceleration of head growth between ages 5 and 48
  months
• loss of previously acquired purposeful hand
  skills between ages 5 and 30 months with the
  subsequent development of stereotyped hand
  movements (e.g., hand-wringing or hand washing)
• loss of social engagement early in the course
  (although often social interaction develops
  later)
• appearance of poorly coordinated gait or trunk
  movements
• severely impaired expressive and receptive
  language development with severe psychomotor
  retardation

15
Diagnostic Criteria Stages

• Stage 1 6-18 months
• Delayed head/brain growth
• Poor muscle tone
• Decreased interest in play/environment

16
Diagnostic Criteria Stages

• Stage 2 12-36 months
• Language regressions
• Social skill regressions
• Motor skill regressions
• Social vacancy stereotyped behaviors emerge
• Stereotypical hand-wringing behavior not always
  evident. May present as hand-to-mouth or similar
  motor activity.
• May become irritable

17
Diagnostic Criteria Stages

• Stage 3
• Stage 3 2-10 years
• Social vacancy decreases
• Profound motor delays

18
Diagnostic Criteria Stages

• Stage 4
• Stage 4 (10yrs)
• Improved social interactive behaviors
• Processing speed issues
• Increased motor problems
• Oral-motor skills decrease
• Often receive feeding tube at this
• point if one is not already in place

We have to be careful not to underestimate their
capabilities. Often their motor limitations
interfere with their abilities. Ex ability to
use sign language
Dr. Ratlif-Schaubb (2008) Nationwide Childrens
Hospital
19
Services

• In recent years, advances in medical technology
  have led to increases in the survival of
  individuals with complex medical conditions
• This causes increasing numbers of children with
  disabilities, and increasing demands for services
• Moore et al (2005)

20
Services

• General trends for medical service use
• Specialist appointments are most frequent in the
  younger age groups, and decline with age
• General practitioner appointments are frequent in
  younger age groups and increase with age
• Predisposing factors (e.g., demographics, social
  structure, genetics) played a large role in
  service use
• Moore et al (2005)

21
Services

• Medical Services
• Seizures
• Anti-seizure medications
• Feeding Disorders
• GERD
• Behavioral issues/agitation/sleep disorders

22
Services

• Physical Therapy
• Usually begin when there is loss of developmental
  milestones
• Range of motion and ambulation
• Deformities and contractures
• Maintaining postural alignment
• Loss of mobility
• Range of motion, transferring, positioning

23
Services

• Occupational Therapy
• Increase the use of the body, especially hands
• 75 of those with Rett Syndrome lose most
  functional use of hands
• Decrease repetitive hand movements
• Feeding skills
• Sensory processing
• Encouraging independence

• A lot of the motor skill regressions can be
  prevented with aggressive OT. Working to decrease
  repetitive hand movements (ie. splits on hands)
  and improve functional hand use could prevent a
  total loss of motor ability.
• Dr. Ratlif-Schaubb (2008)
• Nationwide Childrens Hospital

24
Services

• Nutrition
• Seizure management
• Ketogenic diet
• Osteoporosis
• Supplements
• Constipation

25
Services

• Speech Therapy
• Language development affected by
• General cognitive deficits, auditory processing,
  apraxia, dyarthria, abnormal respiration
• Expressive vs. receptive language abilities
• Increase communication abilities
• Speech of augmentative communication
• Increase socialization/participation

26
Services

• Other potential therapies
• Hydrotherapy
• Music Therapy
• Hippotherapy
• International Rett Syndrome Association Budden
  (1997)

27
Resources

• Rett Syndrome Research Foundation (RSRF)
• Founded in 1999 by a group of parents concerned
  about the lack of research on Rett Syndrome
• the world's leading private funder of Rett
  research.
• In the last five years RSRF has funded 104
  projects at premiere institutions totaling over
  11 million
• organizes the only annual scientific meeting
  devoted to Rett Syndrome.
• Each June RSRF convenes over 100 researchers and
  clinicians from around the world for a three day
  Rett Syndrome symposium
• RSRF Office4600 Devitt DriveCincinnati, OH
  45246Tel [phone]http//www.rsrf.org/abou
  t_rsrf/

28
Resources

• International Rett Syndrome Association
• Stated purpose
• to bring about cures and treatments for Rett
  syndrome AS SOON AS POSSIBLE while taking care of
  the families and individuals living with Rett
  syndrome RIGHT NOW.
• Information, research, family support, awareness,
  advocacy, fundraising

http//www.rettsyndrome.org/index.asp
29
Resources

• Ohios Parent Guide to Autism Spectrum Disorders
• Developed by the Ohio Center for Autism and Low
  Incidence (OCALI) Parent Resource Manual Task
  Force (including Pat Cloppert, Parent Advocate at
  the Nisonger Center)
• This guide was developed and written by parents
  of individuals with autism spectrum disorders.
  The examples provided are from their experiences.
  The information included in this manual is a
  result of their answer to the question
• When your child was first diagnosed, what
  information did you need most?
• http//www.ocali.org/family/fs_res_guide.php

30
Resources

• Girl Power 2 Cure, Inc.
• Girl power 2 Cure, Inc is a non-profit
  organization dedicated to raising funds for
  research for treatments and to find a cure for
  Rett Syndrome. The Foundation will also allocate
  funds to build and manage an interactive website
  where girls can learn about Rett Syndrome, and
  Rett families can find unique resources for their
  girls
• Activities
• Events/Programs
• CD available for purchase
• proceeds benefit Rett research
• http//www.girlpower2cure.org/

31
Resources

• Rett Angels
• Membership based
• A collection of links, current events and news
  items, blogs, pictures and personal stories.
• http//www.rettangels.org/news.php

32
Resources

• The Blue Bird Circle Rett Center at Baylor
  College of Medicine
• One of just a few centers in the United State
  that specializes in Rett Syndrome
• Provides care to women and girls with Rett
  Syndrome worldwide
• Rett syndrome information package available upon
  request
• Contact Information
• 6621 Fannin Street, CC1250Houston,TX
  77030Phone 832-822-RETT (7388)Toll-free
  1-888-430-7388 Fax [phone]email
  rett_at_bcm.edu
• http//www.bcm.edu/pediatrics/index.cfm?Realm9999
  1118This_Templatepedi_home.cfm

33
Bibliography

• Budden, S. (1997). Rett syndrome Habilitation
  and management reviewed. European Child
  Adolescent Psychiatry, 6, 103-107.
• This article examines the different services
  available to individuals with Rett Syndrome, with
  emphasis on the areas of medical, nutritional,
  physical, and speech-language. Each of these
  areas is then subdivided into its different foci
  (e.g., medical deals with seizures, GERD, and
  agitation/behavioral disturbances). Each of the
  remediation techniques/methods discussed has been
  shown via research to be effective in the
  management of some aspect of the disorder.
  Additionally, the article mentions several
  additional therapies that may be helpful to some
  individuals (e.g., hippotherapy, hydrotherapy,
  music therapy). While slightly outdated, this is
  one of the few articles that provides a
  comprehensive overview of different methods to
  remediate some of the characteristics of the
  disorder.

34
Bibliography

• Matson, J. (2007). Current status of differential
  diagnosis for children with autism spectrum
  disorders. Research in Developmental
  Disabilities, 28, 109-118.
• This article provides an overview of recent
  developments regarding diagnosis of children with
  autism spectrum disorders, with emphasis on
  diagnosis in early childhood. The author
  describes common instruments used by clinicians
  for diagnosing on the autism spectrum (e.g. CARS,
  AID-R). Methods currently used for early (birth
  - 4 years) diagnosis are discussed (genetic
  mapping, screening questionnaires) are discussed.
  The article concludes with a review of the range
  of autism spectrum disorders (Aspergers Syndrome,
  Rett Syndrome), with particular attention to
  prevalence rates and diagnostic measures used to
  assess these disorders on the autism spectrum.

35
Bibliography

• Moore, H., Leonard, H., de Klerk, N., Robertson,
  I., Fyfe, S., Christodoulou, J., Weaving, L.,
  Davis, M., Mulroy, S., Colvin, L. (2004) Health
  service use in Rett syndrome. Journal of Child
  Neurology, 19, 42-50.
• This article examines the extent to which
  different factors affect service use by families
  with children who have Rett Syndrome. These
  factors include the following age, maternal
  education, phenotype classification (mild
  atypical, classic, atypical early onset),
  X-inactivation, mutation location, and mutation
  type. The researchers then examined use of the
  following forms of medical service annual rates
  of medical appointments, number of general
  practitioner appointments, number of specialist
  appointments, and annual rates of hospital
  admissions. Based on a multivariate analysis, it
  was determined that phenotype classification,
  maternal education, and X-inactivation were
  significant predictors of the use of medical
  services.

36
Bibliography

• Morrison, J. Anders, T. (1999). Interviewing
  children and adolescents Skills and strategies
  for effective DSM-IV diagnosis. New York
  Guilford Press. 
• This book is designed for clinicians assessing
  children and adolescents. Psychiatric disorders
  typically diagnosed in non-adult populations, as
  outlined in the Diagnostic Statistical Manual
  (DSM) are described at length. The book contains
  an entire chapter on autism spectrum disorders,
  including diagnostic features and diagnostic
  criteria. This chapter is particularly helpful in
  differential diagnostics (e.g. differentiating
  Rett Syndrome from Childhood Disintegrative
  Disorder). The chapter also contains several case
  study vignettes which provide a more
  comprehensive illustration of disorders on the
  autism spectrum. These vignettes, in addition to
  a chapter that offers specific strategies for
  working with youth make this book an essential
  complement to the DSM.

37
Bibliography

• Normura, Y and Segawa, M. (2005). Natural history
  of Rett syndrome. Journal of Child Neurology.
  Vol. 20 (9), pp. 764-8.
• This article gave an historical look at the
  discovery and research behind Rett syndrome. It
  details the typical signs and symptoms present
  during onset, late infancy, early childhood,
  childhood, and adulthood. It also gives
  interesting data on a sleep study of patients
  diagnosed with Rett syndrome and associated
  disorders that have been found in these patients.
  It linked characteristic sleep abnormalities with
  gene components.

38
Bibliography

• Therapies. (2007). International Rett Syndrome
  Association. Retrieved November 16, 2007 from
  http//www.rettsyndrome.org/
• Harris, S., Glasberg, B., Rice, D. (1996).
  Pervasive Developmental Disorders
  Distinguishing among subtypes. The School
  Psychology Review, 25(3), 308-315.