Rett syndrome is usually recognized during early childhood, although the exact age of diagnosis varies between individuals. Many affected children appear to develop relatively typically during the first 6–18 months of life. After this period, developmental progress may slow, followed by the loss of previously acquired skills.
The characteristic regression often occurs between 1 and 4 years of age, although the timing and severity vary. Some children may show signs earlier or later, and genetic testing can help establish the diagnosis before all the typical clinical features have developed. NCBI

Stage 1: Early development (birth to approximately 6–18 months)
During the first few months of life, a baby with classic Rett syndrome may appear to develop normally.

The child may acquire early skills such as:
– Making eye contact.
– Smiling and interacting with caregivers.
– Reaching for objects.
– Sitting with support.
– Babbling and making sounds.

However, some children may have subtle developmental differences that become apparent only in retrospect.
For example, parents may notice reduced interest in toys, slower acquisition of motor skills, or less frequent use of their hands.
These early signs are not specific to Rett syndrome and may occur in several other developmental conditions.

Stage 2: Developmental stagnation and regression (approximately 1–4 years)
This is often the most recognizable period in classic Rett syndrome.
Developmental regression means losing skills that a child had already acquired.
Possible changes include:
– Loss of purposeful hand movements: The child may no longer reach for or manipulate objects as effectively.
– Loss of spoken language: Previously acquired words may disappear, and communication may become increasingly limited.
– Repetitive hand movements: Hand wringing, washing-like movements, clapping, or tapping may replace purposeful hand use.
– Motor difficulties: Sitting, standing, walking, and maintaining balance may become difficult.
– Social and behavioural changes: The child may show changes in interaction, attention, or emotional responses.
– Breathing irregularities: Episodes of breath-holding or hyperventilation may develop, particularly while awake.
Some of these features can resemble autism spectrum disorder, cerebral palsy, or other neurological conditions. This can make early diagnosis challenging.

Stage 3: Stabilization or partial recovery
Following the regression period, many children enter a stage in which the rapid loss of skills slows or stops.
Some individuals show improvements in eye contact, attention, communication, or social interaction. However, difficulties with purposeful hand use, speech, and mobility may persist.
This stage does not mean that the underlying genetic condition has disappeared. Rather, the clinical course may become more stable.

Stage 4: Later motor complications
As individuals grow older, motor difficulties may become more prominent.
Possible complications include:
– Scoliosis, or abnormal curvature of the spine.
– Muscle stiffness or abnormal muscle tone.
– Reduced mobility.
– Joint contractures.
– Feeding difficulties and poor weight gain.
– Constipation and other gastrointestinal problems.
Not every individual develops all these complications. Their severity depends on the person’s clinical course and overall health.

How is Rett syndrome diagnosed?
Diagnosis involves a combination of clinical assessment and genetic testing.
Clinical evaluation includes reviewing developmental milestones, identifying any loss of previously acquired skills, examining hand movements, and assessing walking, communication, and other neurological features.
Genetic testing can identify a pathogenic variant in the MECP2 gene. Testing may include gene sequencing and deletion/duplication analysis. If the findings suggest another genetic condition, a broader genetic panel or genomic test may be appropriate.
A negative MECP2 result does not automatically exclude every Rett-like disorder. The clinical findings and other possible genetic causes must also be considered