Fragile X syndrome: Associated neurological abnormalities and developmental disabilities

-We studied 11 patients (9 males) with cytogenetic diagnosis of fragile X syndrome (FXS) with the purpose of investigating the neural circuitry involved in this condition. The ages ranged from 8 to 19. All the individuals presented large ears, elongated faces and autistic features. Ten patients had severe mental retardation. Attention disorder was found in 10 individuals. Electroencephalographic recordings were abnormal in 6 of 10 patients examined, showing focal epileptiform discharges predominantly in frontal and parietal areas. All patients underwent magnetic resonance imaging studies which were abnormal in 8 of them. The most important abnormalities were reduction of the cerebellar vermis and enlargement of the IV ventricle. Single photon emission computerized tomography (SPECT) was performed in 7 patients and was abnormal in all of them, the most frequent finding being a hypoperfusion of the inferior portions of the frontal lobes. Based on the clinical picture, neuropsychological findings and functional and structural imaging studies we suggest that FXS presents with a dysfunction involving a large area of the central nervous system: cerebellum -basal frontal regions -parietal lobes. The literature points to a disturbance involving the same neural circuitry in patients with autism.KEY WORDS: fragile X syndrome, MRI, SPECT, autism. Síndrome do X frágil: características clínicas, eletrencefalográficas e de imagemRESUMO -Estudamos 11 pacientes (9 do sexo masculino) com diagnóstico citogenético de síndrome do X frágil (SXF) com o objetivo de se investigar o circuito neuronal afetado nesta entidade. As idades variaram de 8 a 19 anos. Todos os indivíduos apresentaram pavilhões auriculares grandes, faces alongadas e traços autistas. Dez deles tinham retardo mental grave. Detectou-se a presença de distúrbio da atenção em 10 pacientes. O eletrencefalograma revelou-se anormal em 6 de 10 indivíduos examinados, mostrando descargas epileptiformes focais predominantemente em áreas frontais e parietais. Todos foram submetidos a ressonância magnética craniana que se revelou anormal em 8. As anormalidades mais importantes foram redução do verme cerebelar e aumento do IV ventrículo. Realizou-se tomografia por emissão de photon único (SPECT) em 7 pacientes. Todos os exames estavam alterados sendo o principal achado a hipoperfusão das porções inferiores dos lobos frontais. Com base no quadro clínico, achados neuropsicológicos e resultados dos exames funcionais e de imagem, sugerimos que a SXF apresenta disfunção de ampla rede neuronal: cerebelo -regiões fronto basais -lobos parietais. A literatura aponta para a presença de distúrbio envolvendo o mesmo circuito neuronal em pacientes autistas. PALAVRAS-CHAVE: síndrome do X frágil, RM, SPECT, autismo.

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“…Other investigators have also noted the benign course of epilepsy and the good response to the treatment in FXS patients 8,17,[24][25][26] .…”

Section: Discussionmentioning

confidence: 86%

Fragile X syndrome: clinical, electroencephalographic and neuroimaging characteristics

Guerreiro

Camargo

Kato

et al. 1998

Arq. Neuro-Psiquiatr.

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“…29 There are variable figures for the prevalence of seizures depending on the cohort under study. Previous studies recruiting from programs focused on epilepsy and neurology clinics reported a broad range of 14% to 44% prevalence, [30][31][32][33][34][35][36][37][38] and genetics clinics reported an intermediate range of 9% to 27%. [39][40][41][42] Larger studies focused on people with FXS in the community or FXS clinics reported lower prevalence rates overall, ranging from 12% to 18%, 29,[43][44][45] and with higher prevalence for male than for female patients.…”

Section: Neurologic Disordersmentioning

confidence: 99%

“…45 and secondary generalization and status epilepticus can occur. 48,49 Seizures are easily controlled 29,31,36,38,42,45,47 and resolve during childhood in the majority of people with FXS. 43,47 Routine EEG screening of people with FXS is not recommended unless the patient presents with behaviors or episodes that might represent seizures.…”

Section: Neurologic Disordersmentioning

confidence: 99%

Fragile X Syndrome: A Review of Associated Medical Problems

et al. 2014

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Fragile X syndrome (FXS) is the most common known genetic cause of inherited intellectual disability and the most common known singlegene cause of autism spectrum disorder. It has been reported that a spectrum of medical problems are commonly experienced by people with FXS, such as otitis media, seizures, and gastrointestinal problems. Previous studies examining the prevalence of medical problems related to FXS have been challenging to interpret because of their marked differences in population, setting, and sampling. Through this comprehensive review, we update the literature by reviewing studies that have reported on prominent medical problems associated with FXS. We then compare prevalence results from those studies with results from a large cross-sectional database consisting of data collected by fragile X clinics that specialize in the care of children with FXS and are part of the Fragile X Clinical and Research Consortium. It is vital for pediatricians and other clinicians to be familiar with the medical problems related to FXS so that affected patients may receive proper diagnosis and treatment; improved care may lead to better quality of life for these patients and their families. Pediatrics 2014;134:995-1005

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“…Various authors reported a 25-40% incidence of seizures (221,222). Generalized tonic-clonic seizures are the most common seizure type.…”

Section: Epileptologymentioning

confidence: 99%

Chromosomal Abnormalities and Epilepsy: A Review for Clinicians and Gene Hunters

et al. 2002

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Summary:Purpose: We analyzed databases on chromosomal anomalies and epilepsy to identify chromosomal regions where abnormalities are associated with clinically recognizable epilepsy syndromes. The expectation was that these regions could then be offered as targets in the search for epilepsy genes.Methods: The cytogenetic program of the Oxford Medical Database, and the PubMed database were used to identify chromosomal aberrations associated with seizures and/or EEG abnormalities. The literature on selected small anomalies thus identified was reviewed from a clinical and electroencephalographic viewpoint, to classify the seizures and syndromes according to the current International League Against Epilepsy (ILAE) classification.Results: There were 400 different chromosomal imbalances described with seizures or EEG abnormalities. Eight chromosomal disorders had a high association with epilepsy. These comprised: the Wolf-Hirschhorn (4p-) syndrome, MillerDieker syndrome (del 17p13.3), Angelman syndrome (del 15q11-q13), the inversion duplication 15 syndrome, terminal deletions of chromosome 1q and 1p, and ring chromosomes 14 and 20. Many other segments had a weaker association with seizures. The poor quality of description of the epileptology in many reports thwarted an attempt to make precise karyotypephenotype correlations.Conclusions: We identified certain chromosomal regions where aberrations had an evident association with seizures, and these regions may be useful targets for gene hunters. New correlations with specific epilepsy syndromes were not revealed. Clinicians should continue to search for small chromosomal abnormalities associated with specific epilepsy syndromes that could provide important clues for finding epilepsy genes, and the epileptology should be rigorously characterized.

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Fragile X syndrome: Associated neurological abnormalities and developmental disabilities

Cited by 67 publications

References 24 publications

Fragile X syndrome: clinical, electroencephalographic and neuroimaging characteristics

Fragile X syndrome: clinical, electroencephalographic and neuroimaging characteristics

Fragile X Syndrome: A Review of Associated Medical Problems

Chromosomal Abnormalities and Epilepsy: A Review for Clinicians and Gene Hunters

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