Rett Syndrome - Initial Diagnosis

Page Contents

• Overview
• Presentations
• Diagnostic Criteria
• Pearls And Alerts
• Practice Guidelines
• Differential Diagnosis
• History And Examination
• Resources

Overview

Presentations

• congenital onset RS – there is no period of normal development; delay is noted early on, or seizures begin and are followed by developmental regression
• late onset RS – regression and/or delay are not noted until 2-4 years of age
• RS with preserved speech and hand skills – not usually diagnosed until later, with milder symptoms
• male RS – a severe neonatal encephalopathy or a more typical Rett-like syndrome seen in XXY males or somatic mosaicism
• provisional RS – thought to be classic RS but in a child not old for the diagnosis to be made
• atypical – early-onset seizures RS (the Hanefield variant, see [Scala: 2005])
• the spectrum of RS continues to widen as more is learned – mild learning disabilities in females and mental retardation in males (syndromic or non-syndromic) are also part of the MECP2-related disorders (see MECP2-related disorders (GeneReviews))

Diagnostic Criteria

• Normal prenatal and perinatal history
• Normal psychomotor development for the first six months
• Normal head circumference at birth
• Postnatal deceleration of head growth in most individuals
• Loss of purposeful hand skills between age six months and 2.5 years
• Hand stereotypies
• Evolving social withdrawal, communication dysfunction, loss of acquired speech, and cognitive impairment
• Impairment or deterioration of locomotion

• Breathing disturbances during waking hours
• Bruxism
• Impairment of sleeping pattern from early infancy
• Abnormal muscle tone associated with muscle wasting and dystonia
• Peripheral vasomotor disturbances
• Progressive kyphosis or scoliosis
• Growth retardation
• Hypotrophic, small, and cold feet and/or hands

• Evidence of a storage disorder, e.g., organomegaly
• Cataract, retinopathy, or optic atrophy
• History of perinatal or postnatal brain damage
• Confirmed inborn error of metabolism or neurodegenerative disorder
• Acquired neurologic disorder caused by severe head trauma or infection
  
  

• Reduction or absence of hand skills
• Loss or reduction of speech (including babble)
• Hand stereotypies
• Loss or reduction of communication skills
• Deceleration of head growth from early childhood
• Regression followed by recovery of social interaction

• Breathing irregularities
• Abdominal bloating or air swallowing
• Bruxism
• Abnormal locomotion
• Kyphosis or scoliosis
• Lower limb amyotrophy
• Cold, discolored, and usually hypotrophic feet
• Night-time screaming and other sleep disturbances
• Inexplicable episodes of screaming or laughing
• Apparently diminished sensitivity to pain
• Intense eye contact and/or eye pointing

Pearls And Alerts

Consider testing for a MECP-2 mutation in girls with moderate or severe mental retardation even without clinical features of RS. [Moeschler: 2006]

Evidence for subtle early developmental abnormalities in girls with RS is beginning to mount. For example, see [Einspieler: 2005] and [Einspieler: 2005].

Practice Guidelines

Differential Diagnosis

• Autism – girls with atypical RS are frequently first diagnosed with autism.
• Angelman syndrome – children with Angelman syndrome often have speech delay, microcephaly, and seizures, although they do not usually exhibit a developmental regression and seizures are a more prominent feature. Sometimes children with Angelman syndrome have positive testing for MECP2 mutations.
• Cerebral palsy – sometimes older girls with spasticity and MR that have been previously diagnosed with CP are found to have RS.
• Infantile form of neuronal ceroid lipofuscinosis (NCL) – see Neuronal Ceroid Lipofuscinosis for more information. Patients with NCL demonstrate a continuing progressive course and have ophthalmologic abnormalities (especially electroretinogram abnormalities).
• Rett syndrome, Hanefield variant – result of CDKL5 gene mutations that produce an atypical RS variant with prominent early-onset seizures. [Scala: 2005] This is a rare mutation type for RS-like features, but should be considered if seizures occur very early in the course of the disease and MECP2 testing is negative.

History And Examination

Resources

Authors

Page Bibliography

Einspieler C, Kerr AM, Prechtl HF.
Is the early development of girls with Rett disorder really normal?.
Pediatr Res. 2005;57(5 Pt 1):696-700. PubMed abstract

Einspieler C, Kerr AM, Prechtl HF.
Abnormal general movements in girls with Rett disorder: the first four months of life.
Brain Dev. 2005;27 Suppl 1:S8-S13. PubMed abstract

Hagberg B, Hanefeld F, Percy A, Skjeldal O.
An update on clinically applicable diagnostic criteria in Rett syndrome. Comments to Rett Syndrome Clinical Criteria Consensus Panel Satellite to European Paediatric Neurology Society Meeting, Baden Baden, Germany, 11 September 2001.
Eur J Paediatr Neurol. 2002;6(5):293-7. PubMed abstract

Moeschler JB, Shevell M.
Clinical genetic evaluation of the child with mental retardation or developmental delays.
Pediatrics. 2006;117(6):2304-16. PubMed abstract / Full Text
This report describes the "optimal clinical genetics evaluation" for children with developmental delay or mental retardation for medical home providers.

Scala E, Ariani F, Mari F, Caselli R, Pescucci C, Longo I, Meloni I, Giachino D, Bruttini M, Hayek G, Zappella M, Renieri A.
CDKL5/STK9 is mutated in Rett syndrome variant with infantile spasms.
J Med Genet. 2005;42(2):103-7. PubMed abstract / Full Text