Pregnancy in a Patient with RETT SYNDROME Mutation: Dilemmas in Management

Rett syndrome, a neurodevelopmental disorder is caused by MECP2 gene mutations inherited sporadically or x linked dominant fashion. It almost exclusively affects girls. Genetic testing can help in preventing recurrence by offering prenatal diagnosis in affected families. We discuss the case of a patient who had such a mutation and discuss her pregnancy outcomes.

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Rett syndrome: a neurodevelopmental disorder

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20192790 ◽

2019 ◽

Vol 6 (4) ◽

pp. 1757

Author(s):

Setu Dagli ◽

Arpita Thakker Adhikari ◽

Mona Gajre

Keyword(s):

Genetic Testing ◽

Developmental Delay ◽

Rett Syndrome ◽

X Chromosome ◽

Genetic Disorder ◽

Neurodevelopmental Disorder ◽

Hand Movements ◽

Global Developmental Delay ◽

Mecp2 Gene ◽

Ataxic Gait

Rett Syndrome is a rare genetic disorder caused by a mutation on the MECP2 gene on the X chromosome. It classically presents with neuroregression, loss of purposeful hand use, stereotypical involuntary hand wringing movements, an ataxic gait and acquired microcephaly with a large proportion of patients developing seizures. The authors present the case of a 3.5 year old girl with severe global developmental delay and regression, loss of purposeful hand use and an ataxic gait for 2 years and seizures since 5 days along with microcephaly with involuntary hand movements but no classic wringing movements with no significant findings on MRI and EEG and diagnosed with Rett Syndrome on the basis of genetic testing.

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Sphingolipid Metabolism Perturbations in Rett Syndrome

Metabolites ◽

10.3390/metabo9100221 ◽

2019 ◽

Vol 9 (10) ◽

pp. 221 ◽

Cited By ~ 1

Author(s):

Cappuccio ◽

Donti ◽

Pinelli ◽

Bernardo ◽

Bravaccio ◽

...

Keyword(s):

Rett Syndrome ◽

Metabolic Profiling ◽

Neurodevelopmental Disorder ◽

Sphingolipid Metabolism ◽

Tandem Mass ◽

Mecp2 Gene ◽

Loss Of Function ◽

Disease Pathogenesis ◽

Blood Samples ◽

Disease Biomarkers

Rett syndrome is a severe neurodevelopmental disorder affecting mostly females and is caused by loss-of-function mutations in the MECP2 gene that encoded the methyl-CpG-binding protein 2. The pathogenetic mechanisms of Rett syndrome are not completely understood and metabolic derangements are emerging as features of Rett syndrome. We performed a semi-quantitative tandem mass spectrometry-based analysis that measured over 900 metabolites on blood samples from 14 female subjects with Rett syndrome carrying MECP2 mutations. The metabolic profiling revealed alterations in lipids, mostly involved in sphingolipid metabolism, and sphinganine/sphingosine, that are known to have a neurotrophic role. Further investigations are required to understand the mechanisms underlying such perturbations and their significance in the disease pathogenesis. Nevertheless, these metabolites are attractive for studies on the disease pathogenesis and as potential disease biomarkers.

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ESOPHAGEAL MOTILITY DISTURBANCES IN CHILDREN WITH RETT SYNDROME: CORRELATION WITH X-LINKED METHYL CPG BINDING PROTEIN (MECP2) GENE MUTATIONS

Journal of Pediatric Gastroenterology and Nutrition ◽

10.1097/01.mpg.0000181946.55344.ff ◽

2005 ◽

Vol 41 (4) ◽

pp. 520-521 ◽

Cited By ~ 1

Author(s):

John E Fortunato ◽

Anil Darbari ◽

John Desbiens ◽

Geni Bibat ◽

Sakkubai Naidu ◽

...

Keyword(s):

Rett Syndrome ◽

Esophageal Motility ◽

Binding Protein ◽

Gene Mutations ◽

Mecp2 Gene ◽

Protein Mecp2

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The Molecular Functions of MeCP2 in Rett Syndrome Pathology

Frontiers in Genetics ◽

10.3389/fgene.2021.624290 ◽

2021 ◽

Vol 12 ◽

Author(s):

Osman Sharifi ◽

Dag H. Yasui

Keyword(s):

Rett Syndrome ◽

Neurodevelopmental Disorder ◽

Gene Mutations ◽

Original Research ◽

Novel Treatments ◽

Conflicting Evidence ◽

Mecp2 Protein ◽

Culture Models ◽

Biologic Function ◽

Cell Culture Models

MeCP2 protein, encoded by the MECP2 gene, binds to DNA and affects transcription. Outside of this activity the true range of MeCP2 function is still not entirely clear. As MECP2 gene mutations cause the neurodevelopmental disorder Rett syndrome in 1 in 10,000 female births, much of what is known about the biologic function of MeCP2 comes from studying human cell culture models and rodent models with Mecp2 gene mutations. In this review, the full scope of MeCP2 research available in the NIH Pubmed (https://pubmed.ncbi.nlm.nih.gov/) data base to date is considered. While not all original research can be mentioned due to space limitations, the main aspects of MeCP2 and Rett syndrome research are discussed while highlighting the work of individual researchers and research groups. First, the primary functions of MeCP2 relevant to Rett syndrome are summarized and explored. Second, the conflicting evidence and controversies surrounding emerging aspects of MeCP2 biology are examined. Next, the most obvious gaps in MeCP2 research studies are noted. Finally, the most recent discoveries in MeCP2 and Rett syndrome research are explored with a focus on the potential and pitfalls of novel treatments and therapies.

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Rett Syndrome without MECP2 Mutation in a Pakistani Girl

Life and Science ◽

10.37185/lns.1.1.77 ◽

2020 ◽

Vol 1 (2) ◽

pp. 3

Author(s):

Rubina Dad ◽

Humaira Aziz Sawal ◽

Arsalan Ahmad ◽

Muhammad Ikram Ullah ◽

Muhammad Jawad Hassan

Keyword(s):

Intellectual Disability ◽

Genetic Testing ◽

Social Behavior ◽

Rett Syndrome ◽

Causative Mutation ◽

Nucleotide Variation ◽

Mecp2 Gene ◽

Pakistani Family ◽

History Of ◽

Electroencephalogram Eeg

Rett syndrome is a rare inherited neurodegenerative disease which mostly affects females but has a lethal impact on males. Rett syndrome is mostly caused by mutations of Methyl CpG binding protein-2 (MECP2) gene located on chromosome Xq28. A 7-year girl from a consanguineous Pakistani family presented with history of abnormal social behavior, tonic colonic seizures, limb'sataxia, intellectual disability, growth retardation and speech abnormalities. Physical and neurological examinations established likely clinical features of Rett syndrome with abnormal electroencephalogram (EEG). Genetic testing of MECP2 gene did not identify any functional nucleotide variation indicating the involvement of another gene mutation in this patient.A consanguineous case of Rett syndrome did not carry the mutation of MECP2 gene. Due to heterogeneity of the phenotype, it is proposed that there might be involvement of another locus for this disease. In future, targeted next generation sequence can be helpful to identify the causative mutation in this patient.

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Rett syndrome: clinical and epidemiological aspects in a Brazilian institution

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2003000600004 ◽

2003 ◽

Vol 61 (4) ◽

pp. 909-915 ◽

Cited By ~ 2

Author(s):

Cristina M. Pozzi ◽

Sergio Rosemberg

Keyword(s):

Rett Syndrome ◽

Clinical Data ◽

Neurodevelopmental Disorder ◽

Mecp2 Gene ◽

Laboratory Studies ◽

Cerebral Malformation ◽

Brazilian Sample ◽

Female Patients ◽

Congenital Form ◽

Frequent Finding

Rett syndrome (RS) is a neurodevelopmental disorder, preferentially found in females and specifically involving the functions on which intelligence and its expression depend - learning, hand use and speech - leaving many others intact. Mutations have been identified at Xq28 on the MECP2 gene (methyl-CpG 2), which selectively silences the expression of other genes whose location is still unknown. This is a study on clinical, diagnostic and epidemiological aspects of RS in a Brazilian sample. It included 33 female patients with chronic encephalopathy without known etiology. RS was diagnosed in 24 patients (72.7%): 17 (70.8%) had classical RS; 5 (20.8%), atypical RS and 2 (8.4%), potential RS. In 9 girls clinical data and/or laboratory studies excluded diagnosis of RS. Among the atypical RS patients, 4 were form fruste and one, congenital form. Among the girls with other encephalopathies, cerebral malformation was the most frequent finding.

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ESOPHAGEAL MOTILITY DISTURBANCES CORRELATE WITH CLINICAL SYMPTOMS OF DYSPHAGIA AND GER INDEPENDENT OF MECP2 GENE MUTATIONS IN RETT SYNDROME

Journal of Pediatric Gastroenterology and Nutrition ◽

10.1097/00005176-200610000-00169 ◽

2006 ◽

Vol 43 (4) ◽

pp. E58

Author(s):

John E. Fortunato ◽

Anil Darbari ◽

John Desbiens ◽

Geni Bibat ◽

Sakkubai Naidu ◽

...

Keyword(s):

Rett Syndrome ◽

Esophageal Motility ◽

Clinical Symptoms ◽

Gene Mutations ◽

Mecp2 Gene

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Red blood cells in Rett syndrome: oxidative stress, morphological changes and altered membrane organization

Biological Chemistry ◽

10.1515/hsz-2015-0117 ◽

2015 ◽

Vol 396 (11) ◽

pp. 1233-1240 ◽

Cited By ~ 10

Author(s):

Lucia Ciccoli ◽

Claudio De Felice ◽

Silvia Leoncini ◽

Cinzia Signorini ◽

Alessio Cortelazzo ◽

...

Keyword(s):

Rett Syndrome ◽

Morphological Changes ◽

Single Gene ◽

Neurodevelopmental Disorder ◽

Gene Mutations ◽

Autism Spectrum ◽

Current Evidence ◽

Loss Of Function ◽

Beneficial Effects ◽

Spectrum Disorders

Abstract In this review, we summarize the current evidence on the erythrocyte as a previously unrecognized target cell in Rett syndrome, a rare (1:10 000 females) and devastating neurodevelopmental disorder caused by loss-of-function mutations in a single gene (i.e. MeCP2, CDKL5, or rarely FOXG1). In particular, we focus on morphological changes, membrane oxidative damage, altered membrane fatty acid profile, and aberrant skeletal organization in erythrocytes from patients with typical Rett syndrome and MeCP2 gene mutations. The beneficial effects of ω-3 polyunsaturated fatty acids (PUFAs) are also summarized for this condition to be considered as a ‘model’ condition for autism spectrum disorders.

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Clinical Stringency Greatly Improves Mutation Detection in Rett Syndrome

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100004200 ◽

2005 ◽

Vol 32 (3) ◽

pp. 321-326 ◽

Cited By ~ 4

Author(s):

Julie Gauthier ◽

Giovana de Amorim ◽

Gevork N. Mnatzakanian ◽

Carol Saunders ◽

John B. Vincent ◽

...

Keyword(s):

Diagnostic Criteria ◽

Rett Syndrome ◽

Mutation Detection ◽

Neurodevelopmental Disorder ◽

Diagnostic Procedures ◽

Diagnostic Tools ◽

Mecp2 Gene ◽

Strict Adherence ◽

Mecp2 Mutation ◽

The Impact

ABSTRACT:Background:Rett syndrome (RTT) is a severe neurodevelopmental disorder of girls, caused by mutations in the X-linked MECP2 gene. Worldwide recognition of the RTT clinical phenotype in the early 1980's allowed many cases to be diagnosed, and established RTT as one of the most common mental retardation syndromes in females. The years since then led to a refinement of the phenotype and the recent elaboration of Revised Diagnostic Criteria (RDC). Here, we study the impact of the presence versus the absence of the use of diagnostic criteria from the RDC to make a diagnosis of RTT on MECP2 mutation detection in Canadian patients diagnosed and suspected of having RTT.Methods:Using dHPLC followed by sequencing in all exons of the MECP2 gene, we compared mutation detection in a historic cohort of 35 patients diagnosed with RTT without the use of specific diagnostic criteria to a separate more recent group of 101 patients included on the basis of strict fulfillment of the RDC.Results:The MECP2 mutation detection rate was much higher in subjects diagnosed using a strict adherence to the RDC (20% vs. 72%).Conclusions:These results suggest that clinical diagnostic procedures significantly influence the rate of mutation detection in RTT, and more generally emphasize the importance of diagnostic tools in the assessment of neurobehavioral syndromes.

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