Fragile X syndrome: clinical, electroencephalographic and neuroimaging characteristics

Abstract

-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.

Enhanced Perfusion in Eyes and Cerebral Perfusion Defects in a Patient with Fragile X Syndrome

“…Thus, reliable tests for early diagnosis and genetic counseling have to be established for the favor of future generations. Physical and neuropsychiatric examination findings in the patient were in concordance with the literature (Guerreiro et al 1998;Artigas-Pallares and Brun-Gasca 2004). EEG findings were abnormal as well.…”

“…The FMR1 gene codes for a cytoplasmic protein called FMRP, which plays role in the cascade of aberrations in neurodevelopment. FMRP is mostly detected in neurons and associated with polyribosomes, including those present in dendrites for synaptic maturation and function (Guerreiro et al 1998). The loss of this specific protein leads to suboptimal structure and function in the central nervous system.…”

Brain Perfusion in Autism Varies with Age

“…Our study concentrates primarily on cortical blood flow in clear cases of autism. Several authors have demonstrated cerebral blood flow abnormalities in autism by SPECT or Wilcox/Tsuang/Ledger/Algeo/Schnurr positron emission tomography technology [Happe and Frith, 1996;Carratala et al, 1998;Guerreiro et al, 1998]. Our study differs significantly by comparing regional blood flow in patients of different ages.…”

Williams syndrome cognitive profile also characterizes Velocardiofacial/DiGeorge syndrome

“…While subjects with WBS tend to be unusually socially outgoing and overly friendly [Jones et al, 2000], subjects with 22q DS are often described as withdrawn [Swillen et al, 1999] or as having flat affect [Bassett et al, 1998], and have an elevated incidence of autisticspectrum diagnoses [Niklasson et al, 2001]. In addition, subjects with both Fragile X and Joubert syndrome also typically possess social and communication problems resembling autistic behavior [Cohen et al, 1991;Holroyd et al, 1991], and these disorders have both have been shown to have decreased cerebellar vermal areas [Holroyd et al, 1991;Guerreiro et al, 1998]. Thus, comparison of neurogenetic disorders with prominent affective components suggests that there may be a possible relationship between posterior vermis size and level of social drive.…”