Rett Syndrome Clinical Presentation

Updated: Mar 20, 2023
  • Author: Bettina E Bernstein, DO; Chief Editor: Caroly Pataki, MD  more...
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The development of Rett syndrome (RS) progresses through 4 stages, which are typically reached at the following ages:

  • Stage I - Developmental arrest (6-18 months)

  • Stage II - Rapid deterioration or regression (1-4 years)

  • Stage III - Pseudostationary (2-10 years)

  • Stage IV - Late motor deterioration (>10 years)

The history varies according to the clinical stage. Typical stage I symptoms are as follows:

  • Parents may report gross motor development delay, disinterest in play, and loss of eye contact

  • Hypotonia may be noted

  • Hand wringing, a hallmark of the disease, typically appears

  • Infants may be reported as placid and calm when compared with healthy infants

  • Early symptoms are often very vague and nonspecific

  • Breath-holding spells, including apneustic breathing and hyperventilation, can occur early

Typical stage II symptoms are as follows:

  • Deterioration may be rapid; sometimes, parents can report specific dates after which their child was no longer healthy; in other cases, deterioration may be slow in onset

  • Stage II can last weeks to months and may be characterized by reports of autisticlike behavior (eg, loss of social interaction and communicative skills, loss of oral language, and loss of purposeful finger and hand use)

  • Parents may note stereotypic hand movements during wakefulness; these are usually midline and consist of hand wringing, clapping, washing, or hand-to-mouth movements

  • Parents or caregivers may also report episodes of breathing irregularities, such as hyperventilation [33] or breath holding

  • Patients may also have seizures and vacant spells that resemble seizures

  • Sleep disorders, intermittent strabismus, and irritability may be noted

Typical stage III symptoms are as follows:

  • Some improvement in behavior, hand use, and communication skills may occur

  • Patients may make good eye contact and make their intent known with whatever communicative skills that remain

  • Despite the improvement, mental impairment and hand stereotypies continue

  • Increasing rigidity, bruxism, and involuntary tongue movements may be reported

  • Motor dysfunction and seizures are frequently reported

  • Episodes of hyperventilation or breath holding may continue

  • Although the child has a good appetite, weight gain is poor

  • Feeding may become more difficult, and almost all patients have some degree of oral motor dysfunction

Typical stage IV symptoms are as follows:

  • No additional deterioration of cognitive skills, communication skills, or hand skills occurs; however, motor problems may increase, including hypertonia, dystonia, and parkinsonian symptoms (eg, bradykinesia, rigidity, and retropulsion)

  • Some patients stop walking

  • Seizure frequency may be reduced


Physical Examination

Physical findings of Rett syndrome (RS) also vary according to the clinical stage of the disorder. Typical findings in stage I include the following:

  • Patients may show gross motor development delay, loss of eye contact, deceleration in head growth (sometimes occurring by age 3 months), deceleration in weight growth (sometimes occurring by age 4 months), deceleration of height growth (sometimes occurring by age 16 months), hypotonia, and hand wringing

  • Infants may appear placid and calm in comparison with healthy infants

  • Cutaneous findings (eg, hypopigmented macules) are not observed on a Wood lamp examination

Typical findings in stage II include the following:

  • Patients may exhibit autisticlike behavior (ie, loss of social interaction and communicative skills with no oral language).

  • Midline hand wringing, clapping, hand washing, or hand-to-mouth movements may be present, along with episodes of hyperventilation or breath-holding

  • Seizures and vacant spells that resemble seizures may also occur, along with intermittent strabismus and irritability

Typical findings in stage III include the following:

  • Patients may have hand stereotypies, rigidity, hyperventilation, breath holding, bruxism, involuntary tongue movements, poor weight gain, and scoliosis

Typical findings in stage IV include the following:

  • Patients may have dystonia, rigidity, muscle wasting, quadriparesis, scoliosis or kyphoscoliosis, loss of ambulation, growth retardation, hyperventilation, and seizures.

  • Improvements may be observed in the frequency and intensity of hand movements

  • Eye contact continues to be preserved and may be the only avenue by which emotions and needs can be communicated