Rett syndrome and autism spectrum disorder (ASD) are both neurodevelopmental conditions that can affect communication, behaviour, and social interaction. Some children with Rett syndrome initially receive an autism diagnosis because the conditions share certain clinical features.
However, Rett syndrome is a distinct genetic disorder characterized by a particular pattern of developmental regression, loss of purposeful hand movements, and other neurological features. Autism spectrum disorder is a broader diagnosis based on persistent differences in social communication and interaction, together with restricted or repetitive behaviours and interests. NCBI

1. Genetic cause
Rett syndrome: Classic Rett syndrome is most commonly associated with pathogenic variants in the MECP2 gene on the X chromosome. These variants disrupt normal brain function and development.
Autism spectrum disorder: Autism is genetically complex. It can arise through the combined effects of many genetic variants, environmental influences, and, in some individuals, identifiable genetic conditions. There is no single gene responsible for all cases of autism.
Genetic testing may be recommended for autistic individuals when clinical features or family history suggest an underlying genetic condition.

2. Developmental regression
Rett syndrome: A characteristic feature is the loss of previously acquired skills after a period of early development. The child may lose purposeful hand use, spoken language, and some motor abilities.
Autism: Some autistic children also experience developmental regression, particularly involving language or social skills. However, regression is not required for an autism diagnosis, and its pattern varies.
The presence of regression alone cannot distinguish Rett syndrome from autism. The overall developmental history and accompanying clinical features are important.

3. Hand movements
Rett syndrome: One of the most distinctive features is the partial or complete loss of purposeful hand skills, accompanied by repetitive, stereotyped movements. These may include hand wringing, washing-like movements, clapping, or tapping.
Autism: Repetitive movements can also occur in autism. Examples include hand flapping, rocking, spinning objects, or repeating particular actions.
The key difference is that in classic Rett syndrome, repetitive hand movements typically emerge as purposeful hand skills are lost.

4. Speech and communication
Rett syndrome: Children may lose previously acquired spoken language. Some individuals retain limited speech, while others rely heavily on eye gaze, gestures, communication boards, or assistive communication devices.
Autism: Communication abilities vary widely. Some autistic individuals have fluent speech, while others have limited or no spoken language. Difficulties may involve both verbal and nonverbal communication.
Therefore, the absence of speech alone cannot establish a diagnosis of Rett syndrome.

5. Motor function and breathing
Rett syndrome: Motor difficulties are common and may include problems with walking, balance, coordination, and purposeful hand use. Abnormal breathing patterns, such as breath-holding or hyperventilation while awake, can also occur.
Autism: Motor coordination difficulties may occur, but they are not defining features of autism. Breathing irregularities of the characteristic type seen in Rett syndrome are not a core diagnostic feature of autism.
These differences can help clinicians determine whether further neurological or genetic evaluation is necessary.

6. How are the conditions diagnosed?
Rett syndrome is diagnosed through clinical assessment using established diagnostic criteria, supported by MECP2 genetic testing when indicated.
Autism is diagnosed through a comprehensive developmental assessment that examines social communication, interaction, behaviour, and developmental history. There is no single genetic test that can diagnose autism in every individual.