Analysis of Hungarian patients with Rett syndrome phenotype for MECP2, CDKL5 and FOXG1 gene mutations

Hadzsiev, Kinga; Polgár, Noémi; Bene, Judit; Komlósi, Katalin; Kárteszi, Judit; Hollódy, Katalin; Kosztolányi, György; Renieri, Alessandra; Melegh, Béla

doi:10.1038/jhg.2010.156

Cited by 17 publications

(12 citation statements)

References 49 publications

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“…Previous studies of the CDKL5 disorder have also reported dysmorphic features including: large deep-set eyes, strabismus, high forehead, full lips, wide mouth, widely spaced teeth and a high palate. 1,4,5,7,13,18,20,22,25,26,[28][29][30]35 Dysmorphic features have been described in other conditions presenting with early-onset encephalopathy, such as those with FOXG1 mutations and in Pitt-Hopkins syndrome (PHS). In those with FOXG1 mutations, subtle, non-specific dysmorphic features have been reported, along with severe microcephaly, which is typical of FOXG1 syndrome but not common in individuals with the CDKL5 disorder.…”

Section: Discussionmentioning

confidence: 99%

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The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy

et al. 2012

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The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n ¼ 86) and females with MECP2 mutations (n ¼ 920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant.

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Section: Discussionmentioning

confidence: 99%

“…1,4,5,7,13,18,20,22,25,26,[28][29][30]35 The presence of typical facial or other features could provide additional assistance in the clinical identification of individuals with a CDKL5 mutation.…”

Section: Introductionmentioning

confidence: 99%

The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy

et al. 2012

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“…In seeming contrast, we also describe a male patient with severe ID, who has inherited this same missense variant from his unaffected mother. The p.(Arg309Trp) variant and associated clinical phenotype has rarely been reported previously . The thorough clinical description of the present six patients enables discussion of the phenotypic effect of this variant.…”

Section: Summary Of Clinical Features For Each Case Focusing On Rtt Amentioning

confidence: 53%

“…The p.(Arg309Trp) variant is rather rare. Only five cases have been previously reported, three of these cases are described thoroughly in this study (patient 2, 3 and 5) there are only two other reports. The two cases not included in this study include a male patient with psychomotor delay and absent speech (parental testing was not performed) .…”

Section: Resultsmentioning

confidence: 73%

The MECP2 variant c.925C>T (p.Arg309Trp) causes intellectual disability in both males and females without classic features of Rett syndrome

et al. 2016

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Missense MECP2 variants can have various phenotypic effects ranging from a normal phenotype to typical Rett syndrome (RTT). In females, the phenotype can also be influenced by the X-inactivation pattern. In this study, we present detailed clinical descriptions of six patients with a rare base-pair substitution affecting Arg309 at the C-terminal end of the transcriptional repression domain (TRD). All patients have intellectual disability and present with some RTT features, but they do not fulfill the clinical criteria for typical or atypical RTT. Most of the patients also have mild facial dysmorphism. Intriguingly, the mother of an affected male patient is an asymptomatic carrier of this variant. It is therefore likely that the p.(Arg309Trp) variation does not necessarily lead to male lethality, and it results in a wide range of clinical features in females, probably influenced by different X-inactivation patterns in target tissues.

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“…Despite it being only one case, the results obtained should be considered very good in terms of the improvements achieved in the initial disabilities of the patient, and the severity of her genotype, although in this disease, the genotype and phenotype are not always well correlated [37,38]. This may be due to the fact that, as described in the Introduction, other genetic alterations may also be responsible for RTT [42].…”

Section: Discussionmentioning

confidence: 88%

Rett Syndrome: Treatment with IGF-I, Melatonin, Blackcurrant Extracts, and Rehabilitation

Devesa¹,

Devesa²,

Carrillo³

et al. 2018

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Abstract:(1) This study describes the good evolution of a 6-year-old girl genetically diagnosed (R106X) with Rett syndrome (RTT), after having been treated with IGF-I, melatonin (MT), blackcurrant extracts (BC) and rehabilitated for 6 months. (2) The patient stopped normal development in the first year of age. The patient showed short stature and weight and fulfilled the main criteria for typical RTT. Despite her young age, there was pubic hair (Tanner II), very high plasma testosterone, and low levels of plasma gonadotrophins. There were no adrenal enzymatic deficits, and abdominal ultrasound studies were normal. The treatment consisted of IGF-I (0.04 mg/kg/day, 5 days/week, subcutaneous (sc)) for 3 months and then 15 days of rest, MT (50 mg/day, orally, without interruption) and neurorehabilitation. A new blood test, after 3 months of treatment, was absolutely normal and the pubic hair disappeared (Tanner I). Then, a new treatment was started with IGF-I, MT, and BC for another 3 months. In this period, the degree of pubertal development increased to Tanner III (pubic level), without a known cause. (3) The treatment followed led to clear improvements in most of the initial abnormalities, perhaps due to the neurotrophic effect of IGF-I, the antioxidant effects of MT and BC, and the cerebral increase in the cyclic glycine-proline (cGP) achieved with administration of BC. (4) A continuous treatment with IGF-I, MT, and BC appears to be useful in RTT.

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Analysis of Hungarian patients with Rett syndrome phenotype for MECP2, CDKL5 and FOXG1 gene mutations

Cited by 17 publications

References 49 publications

The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy

The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy

The MECP2 variant c.925C>T (p.Arg309Trp) causes intellectual disability in both males and females without classic features of Rett syndrome

Rett Syndrome: Treatment with IGF-I, Melatonin, Blackcurrant Extracts, and Rehabilitation

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