‘Rett-like’ label may offer little guidance for patients, study finds
Review of 166 cases finds widely varying genetic causes and symptoms
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The term “Rett-like” may offer little information about a person’s condition or what to expect over time, a systematic review suggests. The label is often used for people who have some features of Rett syndrome but do not meet the criteria for a diagnosis.
Researchers reviewed published reports of 166 people described as Rett-like, most of them female, and found wide differences in their genetic causes and symptoms. Most did not develop typically early in life, and only about one-quarter experienced regression, or the loss of previously acquired skills — a defining feature of Rett syndrome. Walking problems, repetitive hand movements, and seizures were common.
‘Rett-like’ label offers limited insight into diagnosis and prognosis
“‘Rett-like’ commonly describes female individuals with developmental disability, typically with no period of regression, with stereotypies, abnormal gait, and seizures,” the researchers wrote. They found a wide range of genetic causes and concluded that the term has limited clinical value, with little evidence that it helps doctors make a diagnosis or predict how a person’s condition may progress.
The study, “The utility of the term ‘Rett-like’ in relation to Rett syndrome: A systematic review,” was published in Developmental Medicine & Child Neurology.
Rett syndrome is a genetic disorder that mainly affects girls. Most cases are caused by mutations in a gene called MECP2. It can cause symptoms such as developmental problems, communication difficulties, loss of the ability to use the hands for purposeful movements, uncontrolled repetitive hand movements, walking problems, and seizures.
Children with classic Rett syndrome usually develop normally during their first few months of life before development slows or stops. They then experience regression, losing skills they had already learned, particularly speech and the ability to use their hands for purposeful movements. Development generally stabilizes after regression, and children may retain or regain some skills. Later, movement problems typically become more pronounced.
Current diagnostic criteria recognize two main forms of Rett syndrome: classic Rett, the most common Rett type, and atypical Rett. Both require a period of regression followed by stabilization or recovery. However, while classic Rett requires normal early development before regression, children with atypical Rett may already have developmental delays. The two forms also differ in how many other diagnostic features are required. A mutation in MECP2 alone does not establish a Rett diagnosis, and a person can have Rett syndrome without a mutation in that gene.
“Rett-like,” meanwhile, is not a formal diagnosis. The term describes people who have some features of Rett syndrome but do not meet the diagnostic criteria for either the classic or atypical form. However, there is no agreed definition of “Rett-like,” including which features of Rett syndrome a person must have or how many are needed to receive the label.
This raises questions about whether the “Rett-like” label is useful in medical care. The researchers noted that a useful diagnostic label should help identify the cause of a condition, suggest which symptoms may develop, or offer clues about what to expect over time.
Review finds wide range of genetic causes and symptoms
To assess the usefulness of the “Rett-like” label, two researchers in the U.K. reviewed studies published from 2010 through 2025. The review included 66 studies involving 166 people described as Rett-like.
Nearly three-quarters were female (73.5%). A genetic cause was identified in 158 people (95.2%), but the causes varied widely, including chromosomal abnormalities and changes in 47 different genes. MECP2 mutations were identified in only 13 people (7.8%). Changes in ACTL6B were the most common, affecting 21 people (12.7%), followed by changes in GRIA2 in 15 (9%).
Most people (69.3%) had not developed typically early in life, while 26.5% had experienced regression. Walking problems were reported in 64.5% of cases, and repetitive hand movements in 63.9%. Epilepsy was reported in nearly half (48.8%). Loss of previously acquired speech (15.7%) and the ability to use the hands for purposeful movements (11.4%) were reported less often.
Overall, the findings suggest that people described as “Rett-like” may share some Rett syndrome features but can have very different genetic causes and combinations of symptoms. The researchers concluded that the term has “limited clinical value,” with little evidence that it helps establish a diagnosis or predict how a person’s condition may progress.
“We recommend that when the next consensus on the diagnostic criteria for [Rett] is undertaken, consideration is placed on whether the term Rett-like should be encouraged or discouraged in the clinical community,” the researchers concluded.
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