RETT SYNDROME: UPDATE ON DIAGNOSIS MANAGEMENT AND RESEARCH

SAROJINI S. BUDDEN MD, FRCP(C)

Director Rett Syndrome Clinic

Associate Professor Pediatrics

Oregon Health Sciences University

Portland, Oregon

(Presented by Sue Gibson & Kylie Opperman 3/5/06)


RETT SYNDROME

In 1954, Dr. Rett, a Viennese physician, first noticed this syndrome in two girls as they sat in his waiting room with their mothers. He observed these children making the same repetitive hand-washing motions. Curious, he compared their clinical and developmental histories and discovered they were very similar

In 1960, young female patients in Sweden with quite similar symptoms caught the eye of their own physician, Dr. Bengt Hagberg. Dr. Hagberg collected the records of these girls and put them aside, intending to return to them when he had more time to study this curious phenomenon.

But in 1983 an article on RS appeared in the mainstream, English-language journal, Annals of Neurology. Written by Dr. Hagberg and his colleagues, the report finally raised the profile of RS. This article was a breakthrough in communicating details of the disease to a wide audience, and the authors honoured its pioneering researcher by naming it Rett Syndrome.


RETT SYNDROME


RETT SYNDROME

X-linked dominant neurodevelopmental disorder.

NOT progressive, degenerative disorder as once thought

Predominantly affects females

Being identified in males

Sporadic in 99.5 % cases

Hereditary factors in 0.5 %.


RETT SYNDROME – new class of genetic disease

In October of 1999, the discovery of a genetic mutation (MECP2 - methyl-cytosine binding protein) on the X chromosome (Xq28) provided significant insight into the cause of Rett syndrome.

This mutation has now been found in more than 95% of those meeting criteria for typical RS and more than 50% meeting those for atypical RS.


MECP2 GENE

MECP2 encodes a protein called Mecp2 which regulates the expression of other genes by silencing them

Lack of properly functioning protein allows other genes to be expressed in an unregulated way



Diagnosis of Rett Syndrome

Diagnosed with Rett Syndrome if display a certain set of symptoms in their first 3 – 4 years.


Other effects of Rett Syndrome


Variations in time of onset


Stages of Rett Syndrome


CLINICAL FEATURES:
Pre-Regression Stage (<1 Year)

(* ANS involvement)


Developmental Stagnation (9-24 months)


Stage of Regression
(1-4 years)


Early Post- Regression Stage
(Preschool -early school years)


Late Post- Regression stage
(5-15-25 Years ++)


Differential Diagnosis

EARLY STAGES

R/O progressive neurological, muscular metabolic and chromosomal disorders,

and Cerebral Palsy

LATE STAGES

R/O Autism,sensory disturbances, acquired CNS infections and Infantile Spasms


Differential Diagnosis
Autism RS.


RETT SYNDROME:
NEURODEVELOPMENTAL DISORDER

  1. Brain immaturity due to developmental arrest

  2. Immature autonomic nervous system

  3. Growth failure


Autonomic Dysfunction in Rett Syndrome


Autonomic Dysfunction in Rett Syndrome


Growth Failure


Medical management


Seizure Management

50% (5/10) 100% reduction in seizures

30% (3/10) 90% reduction in seizures

20% (2/10) 60-70% reduction in seizures


Sleep Disturbances
Medications for Sleep


Feeding / Nutrition


Management of Drooling


Management of Agitation


Management of Respiratory problems


Management of dystonic spasms and rigidity


Management of Osteoporosis


Interventions

Treatment and therapies should be based on the rationale that Rett Syndrome is NOT a degenerative disease

Each individual has potential to develop new skills

Receptive communicative skills are far better than expressive


Interventions


Therapeutic Interventions

COVENTIONAL APPROACHES – physiotherapy, occupational therapy, speech pathology

OTHER EFFECTIVE THERAPIES-

Factors interfering with communication - Cognitive impairment, delayed latency of response, delayed auditory processing, oral- motor dyspraxia,

dysarthria


Lessons Learned


Useful Links