Background: People with useful speech after regression constitute a distinct group of those with mutation-positive Rett disorder, 6% (20/331) reported among mutation-positive people in the British Survey. We aimed to determine the physical, mental and genetic characteristics of this group and to gain insight into their experience of Rett syndrome. Methods: Clinical and molecular data for people with Rett, aged 10 or more years at follow-up (the study group, n=13), with the ability to converse and a "MECP2" mutation are presented. They were compared with an age-matched control group (n=110), who could not converse and had a pathogenic "MECP2" mutation. Results: The study group differed significantly from the control group with regard to their disease severity (P is less than 0.001); feeding difficulty scores (P is less than 0.001); health scores (P is less than 0.001); epilepsy (P is less than 0.001); head circumference (P is less than 0.004); age at onset of the regression period (P is less than 0.001) (six in the study group did not regress) and mutation frequency (C-terminal deletions P=0.014, R133C P is less than 0.006). The results indicate that favourable skewing of X-inactivation is only present in a small proportion of mild cases. Speech was fragmented with a soft, breathless quality, and all but two had obviously irregular breathing. One person with an R168X mutation preferred signing to speech. All enjoyed interpersonal contact, showing affection and preferring people to objects, clearly distinguishing the condition from autism. Most were habitually anxious. Music was a source of pleasure and relaxation also providing a valuable educational asset. Even in these most able cases, understanding was severely restricted in most and little initiative was shown. Conclusions: While the Rett profile is present in these people they are commonly not classic, and the presence of speech, good head growth and lack of regression may lead to missed diagnoses. A strong association was demonstrated between this milder form of the disease and R133C and C-terminal deletions.