Rett syndrome typically appears in girls who seem to develop normally for the first months of life, then gradually lose skills they had already gained. The most recognizable features are repetitive hand movements (often described as wringing or washing motions), loss of purposeful hand use, loss of speech, and difficulty walking. But the full picture changes significantly as the condition progresses through distinct stages, and the earliest signs can be surprisingly subtle.
The Earliest Signs Are Easy to Miss
Rett syndrome is caused by a mutation in a gene called MECP2, which produces a protein the brain needs to develop normally. The mutation either produces too little of this protein or a damaged version the body can’t use. Because the protein deficit affects brain development gradually, the first signs don’t look alarming. Between 6 and 18 months of age, babies may make less eye contact, lose interest in toys, or show delays in sitting or crawling. Many parents and even pediatricians don’t notice anything unusual during this window.
However, closer analysis has revealed that the problems start earlier than they appear. Researchers who reviewed home videos of infants later diagnosed with Rett syndrome found that all of them showed subtle problems with body movements from birth through 6 months, even when they appeared to be hitting milestones on time. This first stage can last anywhere from a few months to a full year before more obvious changes begin.
What Regression Looks Like
The most alarming phase usually hits between ages 1 and 4. Children begin losing abilities they had previously developed, sometimes rapidly over weeks, sometimes more gradually over months. Purposeful hand movements and speech are usually the first skills lost. A child who had been reaching for objects, feeding herself, or babbling will stop doing those things. Even babbling counts as lost language in the diagnostic criteria, so this regression can be identified in children who hadn’t yet spoken their first words.
During this stage, the hallmark hand movements emerge. These are repetitive, involuntary motions that replace the purposeful hand use the child once had. They look different from child to child but commonly include wringing (twisting the hands together as if washing them), squeezing, clapping, tapping, mouthing the hands, or rubbing them together. These movements are nearly constant during waking hours and are one of the most visually distinctive features of the condition.
Other changes appear in this stage too: head growth slows noticeably, coordination and movement deteriorate, and some children begin hyperventilating, screaming, or crying without an obvious trigger. Social interaction drops off. For parents, this period often feels like watching their child slip away.
Slowed Head Growth
One of the clinical markers that often prompts a closer look is deceleration of head growth. In girls with classic Rett syndrome, average head circumference falls progressively below the norm, reaching about 2 standard deviations below average by age 4 and stabilizing near 3 standard deviations below average after age 8. That said, the degree varies. About 20% of girls with classic Rett syndrome show less than 1 standard deviation of decline by age 6, meaning the change can be mild enough to go unnoticed on a growth chart. In milder variant forms, head circumference often stays within normal limits entirely.
Breathing Patterns
Irregular breathing is one of the more unsettling features of Rett syndrome, and it only occurs while the person is awake. The predominant pattern involves episodes of hyperventilation followed by breath-holding or breathing against closed airways. These episodes can look frightening: the person may breathe very rapidly, then hold their breath long enough to turn slightly blue. During sleep, breathing tends to normalize, though some individuals experience obstructive pauses during sleep as well. The waking-only pattern is distinctive enough that it’s considered a supportive feature when making a diagnosis.
Scoliosis and Seizures
Spinal curvature develops in the majority of people with Rett syndrome and worsens with age. Among 4-year-olds in one large study of over 900 girls with classic Rett syndrome, 28% already had measurable scoliosis. By age 13 and above, that number climbed to 79% or higher. Severe scoliosis affected about 27% of the study population overall, rising from 13% of 9-year-olds to over 40% of those in their late teens. This progression often becomes one of the most significant orthopedic challenges in long-term care.
Seizures are also common. Epilepsy is recognized as a frequent co-occurring condition, though its onset and severity vary widely depending on the specific genetic mutation involved.
How Communication Changes
Despite losing spoken language, many people with Rett syndrome develop a striking ability to communicate through eye gaze. This is so characteristic that “intense eye communication” and “eye pointing” are listed among the supportive diagnostic criteria. Over time, particularly after the most rapid phase of regression passes, children often gradually regain eye contact and develop nonverbal communication skills. Many families and caregivers describe feeling that the person with Rett syndrome understands far more than they can express, and eye-tracking technology has increasingly been used to give them a way to make choices, answer questions, and participate in their environment.
The Four Stages Over Time
After the early onset and rapid regression stages, Rett syndrome enters a plateau phase that can last for years or even decades. Motor problems and seizures may remain, but some social and communication skills stabilize or modestly improve. Many individuals settle into a pattern where their abilities, while significantly affected, remain relatively consistent for long stretches.
A later stage brings further motor deterioration. Muscle tone may become increasingly abnormal, scoliosis progresses, and some individuals who had retained the ability to walk may lose it. Cognitive and communication abilities, however, don’t typically decline further during this phase. Other features that can appear at various points include teeth grinding during waking hours, disturbed sleep, small and cold hands and feet, poor circulation in the extremities, growth delays, constipation, and episodes of inappropriate laughing or screaming.
Diagnosis and Variants
A diagnosis of classic Rett syndrome requires a clear period of regression followed by stabilization, along with all four main criteria: loss of purposeful hand skills, loss of acquired language, gait problems or inability to walk, and stereotypic hand movements. Genetic testing for the MECP2 mutation can confirm the diagnosis, and in some cases, the mutation is identified before regression has clearly begun. When that happens in a child under 3, the diagnosis is considered “possible” and reassessed every 6 to 12 months. If no regression appears by age 5, the diagnosis is reconsidered.
Atypical or variant forms exist as well. These require at least two of the four main criteria plus five of eleven supportive features, which include breathing disturbances, teeth grinding, sleep problems, abnormal muscle tone, scoliosis, growth delays, cold extremities, inappropriate laughing or screaming spells, reduced pain response, and intense eye communication. Variant forms can look quite different from classic Rett syndrome, with milder or more selective symptoms.
Life Expectancy
Rett syndrome was once considered a condition with a dramatically shortened lifespan, but survival data tells a more encouraging story. Analysis of the North American Rett Syndrome Database found that approximately 70% of individuals survived to age 35. Australian population data showed nearly 78% survival to age 25. Survival has also improved across generations: among those born in the 1970s, about 75% were still alive at follow-up, compared to nearly 90% of those born in the 1990s, reflecting advances in medical care and monitoring. People with atypical Rett syndrome had significantly better survival rates, with only about 4% mortality compared to roughly 18% in those with the classic form.