Rett Syndrome - Distribution of Phenotypes with Special Attention to the Preserved Speech Variant

Abstract

Rett syndmme -Preserved speech i So far the Norwegian series of listed females with a verified or tentative diagnosis of Rett syndrome comprises 94 individuals (October 1994). Wty-one of these have been thoroughly' assessed, both clinicaJly, neurophysiologically and biochemically. ?kro individuals did not fulfil the criteria of Rett syndrome, and were excluded. Hence, the present sample cornprises 49 females.Since early diagnosis is usually considered tentative, a l l girls included were above 2 '/2 years. The mean age was 1 ]/a ( y d m o n t h s ) and the range was 2/7-46/11, Tlmty-six of the females fulfilled the critmia of classical Rett syndrome, and 13 belong to the Reff variant group (1). Three of them were c I W e d as having the forme h t e variant with a more mdd and protracted clinical course. Six girls showed congenital o w t , two of them were sisters. Two of the females have the early onset variant, and finally two @rk have the preserved speech variant.The sample presented comprises a substantial part of the known Norwegian population of girls and women with Rett syndrome. It includes fewer than expected forme hste variants. The reasons for this may be that the delineation towards other variants can be d~£6cult to draw (e.9. towards the early seizure variant and the p& s p x h variant). Another possibility is that the age dstribution is skewed, favoring females with earlier onsets. It might also be that the forme fruste variants have a different genetic etiology than classical Rett syndrome, and therefore have a different incidence in different geographical areas.The fact that six &Is belong to the congenital variant implies that h c i a n s should be aware of Reff syndrome syrnptomatology even in girls who appeared delayed h m birth.The developmental and the present chical status of the two girls with prae.mil speech revealed symptoms and signs convincing of Rett syndrome. The speech of one of the girls, aged 16 years, is characterized by echolalia and little spontaneous use. It consists mainly of short sentences, typically repeating parts h m the same narratives, such as Winnie the Pooh, for many years. Most utterances appear in ritualized dialogues that are initiated by a partner -usually one of the parents -who facilitates the girl's speech by beghning utterances that she finishes. Although these dialogues may contain considerable variation in vocabulary use, the only genuinely self-initiated utterances are "I am hungry" and "I am thirsty".The other girl is five years old. She used several words at eight months, and long sentences before speech became sparse and was reduced to babbling mund two years of age. She started to speak again at 3 '/2 years, initially with single-word utterances, and mainly to express needs. At the age of five years she speaks in short sentences, but still only to express needs.In spite of their much larger speech repertoire than other females with Rett syndrome, the two girls with preserved speech have limited pragmatic functions, and truly spontaneous speech is mainly ...

Effects ofMECP2mutation type, location and X‐inactivation in modulating Rett syndrome phenotype

“…There are also a number of supportive criteria for diagnosis of RTT, some of which are shown in Table I [Trevathan and Moser, 1988]. RTT shows a large degree of variation in its clinical manifestations, from “classical” cases, to a range of less or more severely affected “atypical” cases [Hagberg et al, 1985; Goutiéres and Aicardi, 1986, 1987; Trevathan and Moser, 1988; Skjeldal et al, 1995]. Variation can arise in the age of onset, with severe onset from birth in some atypical RTT cases [Goutiéres and Aicardi, 1986, 1987], and late regression in others [Percy et al, 1987].…”

Three Rett patients with both MECP2 mutation and 15q11–13 rearrangements

“…Inability to speak is a cardinal feature of Rett syndrome, 11 but some girls, over the years, recover the ability to speak, improving at the same time the use of their hands. 12,13 These patients are grouped together under the heading of preserved speech variant (PSV) of Rett syndrome. 14 About 80% of Rett syndrome cases and 50% of PSV have a de novo mutation in the transcriptional silencer MECP2 gene, classifying Rett syndrome as a monogenic X-linked dominant disorder.…”

Preserved speech variants of the Rett syndrome: Molecular and clinical analysis

“…Girls affected by the Rett syndrome have long been considered unable to speak: the symptom of alalia was one of the cardinal features in a definition which was agreed upon by a number of professionals from all over the world [Trevathan and Moser, 1988], including one of us (M.Z.). However, more extensive clinical experience has subsequently suggested that the phenotype of Rett syndrome could be wider and include some girls who, over the years, recover the ability to speak in short or even more structured phrases, improving, at the same time, the use of their hands [Zappella, 1992; Zappella, 1994; Skjeldal et al, 1995; Zappella, 1997]. The main clinical feature of these patients was represented by their ability to speak; as a consequence it was suggested that these cases could be grouped together under the heading of preserved speech variant (PSV) of the Rett Syndrome [Zappella, 1992].…”