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INTRODUCTION: Thyroid function in Rett syndrome (RTT) has rarely been studied with unanimous results. However, this aspect is of great concern regarding the effect thyroid hormones (TH) have on proper mammalian brain development. OBJECTIVE: To evaluate the prevalence of abnormalities of thyroid function in a cohort of children with RTT. PATIENTS AND METHODS: Forty-five consecutive Caucasian girls (mean age: 8.6 ± 5.3 years, range: 2.0-26.1) meeting the clinical criteria for RTT were recruited. In all of the subjects, we evaluated the serum concentrations of free-T3 (FT3), free-T4 (FT4), thyroid-stimulating hormone (TSH), thyroperoxidase autoantibodies, thyroglobulin autoantibodies (TgA), and TSH receptor (TSHr) autoantibodies. The results were compared with a group of 146 age-matched healthy Caucasian children and adolescent girls (median age: 9.5 years, range: 1.8-14.6) from the same geographical area. RESULTS: Mean FT3 and TSH levels were not significantly different between the RTT patients and controls. Nevertheless, FT4 levels were significantly higher in RTT patients than in controls (p < 0.005). In particular, 17.7% showed FT4 levels higher than the upper reference limit (vs. 0.7% of controls, p < 0.0001), whereas 12 patients (26.7%) showed higher FT3 levels than the upper reference limit, significantly differing in respect to controls (2.0%, p < 0.0001). Finally, 5 patients (11.1%) showed higher levels of TSH, statistically differing from the control subjects (2.0%, p < 0.0001). However, evaluating the patients on the basis of different RTT genotype subgroups, patients with CDKL5 deletions showed significantly higher FT4 values than patients with MeCP2 deletions (p < 0.05). On the other hand, patients with other types of MeCP2 mutations also showed FT4 levels significantly higher than patients with MeCP2 deletions (p < 0.05). In fact, out of 8 patients with FT4 levels higher than the upper references limit, 3 of them presented with CDKL5 deletions (3 patients, 37.5%), 4 (50%) had MeCP2 mutations, and 1 (12.5%) belonged to the subgroup of MeCP2 deletions. However, when analyzing FT3 levels of the 12 patients showing higher FT3 levels than the upper references limit, 6 (50%) belonged to the subgroup with MeCP2 mutations, 4 (33.3%) to the subgroup with MeCP2 deletions, and 2 (16.7%) to the subgroups with CDKL5 deletions. Furthermore, no patient with RTT was positive for antithyroglobulin autoantibodies, antithyroid peroxidase, or anti-TSHr, with no statistical differences in respect to the controls. L-thyroxine treatment was not necessary for any patient. CONCLUSIONS: Abnormalities of thyroid function are not rare in RTT. The possible relationship between these disorders and the RTT phenotype should be confirmed and studied. Children with RTT should be screened for potential thyroid dysfunction.
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Autoanticorpos/sangue , Síndrome de Rett/sangue , Glândula Tireoide/metabolismo , Hormônios Tireóideos/sangue , Adolescente , Adulto , Sequência de Bases , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Proteína 2 de Ligação a Metil-CpG/genética , Proteína 2 de Ligação a Metil-CpG/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Síndrome de Rett/genética , Síndrome de Rett/patologia , Deleção de Sequência , Glândula Tireoide/patologiaRESUMO
OBJECTIVE: A growing number of studies on deaf children with cochlear implant (CI) document a significant improvement in receptive and expressive language skills after implantation, even if they show language delay when compared with normal-hearing peers. Data on language acquisition in CI Italian children are still scarce and limited to only certain aspects of language. The purpose of this study is to prospectively describe the trajectories of language development in early CI Italian children, with particular attention to the transition from first words to combinatorial speech and to acquisition of complex grammar in a language with rich morphology, such as Italian. DESIGN: Six children, with profound prelingual deafness, provided with CI, between 16 and 24 months of age were prospectively assessed and followed over a mean period of up to 34.8 months postimplant. During follow-up, each child received between four to five individual language evaluations through a combination of indirect procedures (parent reports of early lexical and grammar development) and direct ones (administration of standardized receptive and expressive language tests with Italian norms and collection of spontaneous language samples). RESULTS: In relation to chronological age, the acquisition of expressive vocabulary was delayed. However, considering the duration of hearing experience, most CI participants showed an earlier start and faster growth of expressive rather than receptive vocabulary in comparison with typically developing children. This quite atypical result persisted right up until the end of the follow-up. The acquisition of expressive grammar was delayed relative to chronological age, though all but one CI participant achieved the expected grammar level after approximately 3 years of CI use. In addition, the rate of grammar acquisition was not homogeneous during development, showing two different paces: one comparable with normal hearing in the transition from holophrastic to primitive combinatorial speech and a much slower one to attain more advanced levels of morphosyntactic control. CONCLUSION: From a rehabilitative viewpoint, our results suggest the importance of implementing rehabilitation in lexical comprehension, even when expressive vocabulary appears to be within normal range. Moreover, assessment of language acquisition in CI Italian children should focus on those grammar aspects that are more vulnerable to early acoustic deprivation (such as free and bound morphology) to ensure enhanced language therapy planning.
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Implantes Cocleares , Surdez/reabilitação , Desenvolvimento da Linguagem , Pré-Escolar , Implante Coclear , Surdez/complicações , Feminino , Humanos , Lactente , Itália , Transtornos do Desenvolvimento da Linguagem/etiologia , Modelos Lineares , Estudos Longitudinais , Masculino , Testes Neuropsicológicos , Estudos Prospectivos , VocabulárioRESUMO
Rett syndrome (RTT) is a devastating neurodevelopmental disorder that affects one in ten thousand girls and has no cure. The majority of RTT patients display mutations in the gene that codes for the methyl-CpG-binding protein 2 (MeCP2). Clinical observations and neurobiological analysis of mouse models suggest that defects in the expression of MeCP2 protein compromise the development of the central nervous system, especially synaptic and circuit maturation. Thus, agents that promote brain development and synaptic function, such as insulin-like growth factor 1 (IGF1), are good candidates for ameliorating the symptoms of RTT. IGF1 and its active peptide, (1-3) IGF1, cross the blood brain barrier, and (1-3) IGF1 ameliorates the symptoms of RTT in a mouse model of the disease; therefore they are ideal treatments for neurodevelopmental disorders, including RTT. We performed a pilot study to establish whether there are major risks associated with IGF1 administration in RTT patients. Six young girls with classic RTT received IGF1 subcutaneous injections twice a day for six months, and they were regularly monitored by their primary care physicians and by the unit for RTT in Versilia Hospital (Italy). This study shows that there are no risks associated with IGF1 administration.
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UNLABELLED: Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting almost exclusively females. The Hanefeld variant, or early-onset seizure variant, has been associated with mutations in CDKL5 gene. AIMS: In recent years more than 60 patients with mutations in the CDKL5 gene have been described in the literature, but the cardiorespiratory phenotype has not been reported. Our aim is to describe clinical and autonomic features of these girls. METHODS: 10 girls with CDKL5 mutations and a diagnosis of Hanefeld variant have been evaluated on axiological and clinical aspects. In all subjects an evaluation of the autonomic system was performed using the Neuroscope. RESULTS: Common features were gaze avoidance, repetitive head movements and hand stereotypies. The autonomic evaluation disclosed eight cases with the Forceful breather cardiorespiratory phenotype and two cases with the Apneustic breather phenotype. CONCLUSIONS: The clinical picture remains within the RTT spectrum but some symptoms are more pronounced in addition to the very early onset of seizures. The cardiorespiratory phenotype was dominated by Forceful breathers, while Feeble breathers were not found, differently from the general Rett population, suggesting a specific behavioral and cardiorespiratory phenotype of the RTT the Hanefeld variant.