General Information (including ICD-9/-10 Codes)

Description :

• degenerative disease of white matter, progressive disease presenting as dementia and ataxia

Also called :

• Rett's disorder

ICD-9 Codes :

• 330.8 other specified cerebral degeneration in childhood

ICD-10 Codes :

• F84.2 Rett's syndrome

Who is most affected :

• girls 6 months to 2 years, affects only females
• males affected with mutation of MECP2 gene usually die; case report of Rett's syndrome in male with somatic mosaicism can be found in Lancet 2000 Sep 2;356(9232):830

Incidence/Prevalence :

• prevalence of 6-7 cases per 100,000 females

Causes and Risk Factors

Causes :

• X-linked trait, no enzymatic deficiency or other metabolic explanation has been identified
• most are de novo mutations ( 1 )

Complications and Associated Conditions

Complications :

• cardiac ( 1 )
  • sudden cardiac death
  • prolonged QT
  • bradycardia
• neurologic ( 2 )
  • seizures
  • loss of purposeful hand movements
  • abnormal respiration
  • motor deterioration (wheelchair-bound in adolescence)

History

Chief Concern (CC) :

• loss of previously acquired hand skills
• loss of social engagement (child no longer wants to interact with others)
• poorly coordinated gait and trunk movements
• difficulty expressing and understanding language (severely impaired expressive and receptive language development)
• severe psychomotor retardation
• loss of purposeful hand movements
• normal perinatal history

Physical

General Physical :

• autistic behavior, microcephaly (slowed growth in head circumference), peculiar wringing motion of the hands
• serial exams show child who developed normally at first, then severely slowed development and deterioration
• deceleration of head growth during early childhood has been considered a necessary diagnostic criterion, but in series of 450 cases, 12 (2%) did not have this criterion (Annual Meeting of American Pediatric Society and Society for Pediatric Research 1999 May 1-4 submitted abstract in Pediatric Notes 1999 Apr 29;23(17):68)

Diagnosis

Imaging studies :

• normal brain MRI

EKG :

• prolonged QT reported in 9 of 14 girls with Rett syndrome (Arch Dis Child 1999 May;80(5):470 in Pediatric Notes 1999 Jun 3;23(22):87)

Prognosis

Prognosis :

• phenotypic presentation varies considerably, based on cohort of 120 females with Rett syndrome and metyhyl-CpG binding protein-2 (MECP2) mutations
  • 12 (10%) never learned to sit, others first sat between 6-39 months of age, 6 (5%) lost ability to sit
  • 54 (45%) never learned to walk, rest walked at 10-48 months (median 19 months), 6 lost ability to walk
  • first words spoken at 6-36 months, ability to speak lost at median 24 months
  • 19 (16%) never had good hand function, 13% had preserved hand function
  • loss of hand function or language rarely occurred after age 4 years
  • Reference - Brain Dev 2003 Aug;25(5):346 in Pediatric Notes 2003 Sep 4;27(36):144

Treatment

Treatment overview :

• symptom relief
  • physical therapy for muscular dysfunction
  • medication for seizure control
  • behavior therapy for self-coping

Medications :

• L-carnitine for 8 weeks improved wellbeing in randomized placebo-controlled crossover trial of 35 patients with Rett syndrome (J Child Neurol 1999 Mar;14(3):162 in Altern Ther Health Med 2003 Sep-Oct;9(5):22)
• melatonin does not appear to provide clinically meaningful benefit in patients with secondary sleep disorders (level 2 [mid-level] evidence)
  • systematic review of 12 randomized trials of melatonin in patients with chronic medical or psychiatric disorder considered likely to cause sleep disorder
  • underlying disorders studied in only 1 or 2 trials each and included developmental disability, neurological impairment, mild cognitive impairment, Rett syndrome, tuberous sclerosis, dementia, Alzheimer's disease, major depression, schizophrenia, and chronic whiplash syndrome
  • 9 trials used crossover design with 6 to 44 patients per trial, 3 parallel trials had sample sizes of 33, 81 and 157 patients
  • melatonin associated with non-significant reduction in sleep onset latency of 13.2 minutes in meta-analysis of 6 trials with 163 patients limited by heterogeneity
  • melatonin associated with statistically significant 2% improvement in sleep efficiency (time spent asleep out of time spent in bed) in meta-analysis of 6 trials with 316 patients
  • Reference - BMJ 2006 Feb 18;332(7538):385 full-text, editorial can be found in BMJ 2006 Feb 18;332(7538):373, commentary can be found in BMJ 2006 Mar 4;332(7540):550

Prevention and Screening

Screening :

• universal newborn screening impractical
  • parents of an affected child should be offered prenatal diagnosis for subsequent pregnancies
  • Reference - J Child Neurol 2005 Sep;20(9):779

References including Reviews and Guidelines

General references used :

• 1. Segawa M, Nomura Y. Rett syndrome. Curr Opin Neurol. 2005 Apr;18(2):97-104.
• 2. Chahrour M, Zoghbi HY. The story of Rett syndrome: from clinic to neurobiology. Neuron. 2007 Nov 8;56(3):422-37.

Reviews :

• review can be found in Neurol Clin 2002 Nov;20(4):1125
• review of management of Rett syndrome with a controlled multi-sensory environment can be found in Int J Adolesc Med Health 2004 Jan-Mar;16(1):5
• review of clinical manifestations and stages of Rett syndrome can be found in Ment Retard Dev Disabil Res Rev 2002;8(2):61

Guidelines :

• American Academy of Neurology practice parameter on evaluation of the child with global developmental delay can be found in Neurology 2003 Feb 11;60(3):367
• guidelines for reporting clinical features in cases with MECP2 mutations can be found in Brain Dev 2001 Jul;23(4):208

Patient Information

Patient information :

• handout including organizations for more information from National Institute of Neurological Disorders and Stroke (NINDS)