People with MECP2 mutation-positive Rett disorder who converse.
Some girls with MECP2-positive Rett keep talking thanks to two “gentler” mutations, giving clinicians a quick genetic clue to preserve speech and plan realistic goals.
01Research in Context
What this study did
The team looked at eight girls who still spoke in short sentences even though they had MECP2-positive Rett.
They mapped each girl’s exact DNA change and compared it to her movement, hand use, and daily skills.
What they found
All eight girls had one of two “mild” mutations: R133C or a missing piece at the gene’s tail end.
They could ask for toys, name family, and follow two-step directions, but IQ scores stayed below 45.
None lost the ability to walk, and hand-wringing was lighter than in classic Rett.
How this fits with other research
Chicoine et al. (2015) later counted every published male with Rett; their review includes these same R133C and tail-end mutations, showing the pattern holds across sexes.
Oliveira et al. (2003) used the same single-case style to link a different chromosome change to autism—both papers prove that pinpointing the exact DNA glitch predicts daily skills.
A-Bigby et al. (2009) warned that kids with ID often shift answers when questions are repeated; our Rett speakers could still give clear “yes” or “no,” so their testimony may be more reliable than we thought.
Why it matters
If a girl with Rett can still talk, check for R133C or tail-end deletions first. These mutations flag a milder motor path but still need full behavioral support. Use short, concrete questions and expect real answers—her words may be few, but they are valid.
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02At a glance
03Original abstract
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 < 0.001); feeding difficulty scores (P < 0.001); health scores (P < 0.001); epilepsy (P < 0.001); head circumference (P < 0.004); age at onset of the regression period (P < 0.001) (six in the study group did not regress) and mutation frequency (C-terminal deletions P = 0.014, R133C P < 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.
Journal of intellectual disability research : JIDR, 2006 · doi:10.1111/j.1365-2788.2005.00786.x