RTT is a severe neurodevelopmental disorder, mostly affecting females. However, there are also rare cases of boys and adult males with RTT (1). The most important clinical signs are impairment in cognition, motor control and communication skills. The so-called classical form of RTT is characterised by an apparently normal development the first 6-18 months of life followed by regressive loss of abilities alongside autistic behaviour, at least in the early phases. Furthermore, loss of motor skills, loss of other acquired skills such as purposeful hand function, deceleration of head growth and later the appearance of stereotypic hand movements and respiratory dysfunction are all very common clinical features. A majority of those affected also suffer from epilepsy. In many cases the epilepsy is complicated and difficult to treat. Dysfunction in the autonomic nervous system is also common.
The diagnosis of classical RTT was originally based upon eight mandatory and eight supportive clinical criteria (2). These criteria were revised in 2010 (3) and were limited to the obligatory presence of a period of regression and four main criteria: Partial or complete loss of acquired purposeful hand skills and speech, gait abnormalities and stereotypic hand movements.
In recent years a substantial number of RTT cases have been published and the phenotypic spectrum of RTT has evolved. As early as 1994, the diagnosis included both classical RTT and so-called RTT variants. (4). In the last decade, the term RTT-like disorders has been used for individuals sharing many of the clinical characteristics with RTT, but not fulfilling all the diagnostic criteria. In contrast to classical and atypical RTT, the term RTT-like disorders is not clearly defined (5). This has created confusion and discussions about the concept of diagnosis and RTT.