Biomedical subjects

Roberto Canitano

Publications and source records attributed to Roberto Canitano.

8 recordsLinked to original sources

PubMed2025

AUTS2-related syndrome: Insights from a large European cohort.

PURPOSE: AUTS2-related syndrome is characterized by developmental delay, autism spectrum disorder, and intellectual disability. From alternative promoters, AUTS2 encodes 2 distinct long and short isoforms encoding a putative transcriptional activator. METHODS: Through a European collaborative study, we collected clinical and genotype data on the largest AUTS2-related syndrome cohort of 58 patients harboring genomic rearrangements or single-nucleotide variants (SNVs). RESULTS: Pathogenic SNVs were recurrently found in individuals from different countries, suggesting mutational hotspots. Independent of the underlying defect at the AUTS2 locus, we observed that autistic behavior, hyperactivity, learning difficulties, and speech delay are common features of AUTS2-related syndrome. Among patients with SNVs, individuals carrying pathogenic variants affecting both longer and shorter AUTS2 transcripts showed a recognizable phenotype with microcephaly, brachycephaly, microretrognathia, broad nasal base, and anteverted nares. Behavioral disorders were more common in patients with variants affecting only the longer isoform. Arthrogryposis and stiff movements were only observed in patients with SNVs. CONCLUSION: This study provides a comprehensive clinical characterization of AUTS2-related syndrome, reveals few genotype-phenotype correlations, and suggests that the disruption of the 2 distinct AUTS2 transcripts has a different impact on the clinical phenotype.

Humans↗

PubMed2007

Tics and Tourette syndrome in autism spectrum disorders.

Autism spectrum disorders (ASDs) are more frequently associated with tic disorders than expected by chance. Variable rates of comorbidity have been reported and common genetic and neurobiological factors are probably involved. The aim of this study was to determine the rate of tic disorders in a clinical sample (n = 105) of children and adolescents with ASDs and to describe the clinical characteristics of a group with comorbid ASDs and tics (n = 24). The overlap between tics and other repetitive movements and behaviors in ASDs was carefully assessed. Among individuals with ASDs, 22 percent presented tic disorders: 11 percent with Tourette disorder (TD), and 11 percent with chronic motor tics. All had various degrees of cognitive impairment. An association between the level of mental retardation and tic severity was found. It is concluded that the occurrence of tics in ASDs should not be overlooked and should be carefully evaluated.

Adolescent↗

PubMed2006

Epilepsy in autism spectrum disorders.

Epilepsy is quite common in autism spectrum disorders, and it is increasingly recognized as an additional clinical problem that must be dealt with. The rate of comorbidity varies, depending upon the age and type of disorder, and currently the conservative estimate of comorbidity cases is 20-25% of the whole spectrum. Major risk factors for seizure occurrence are mental retardation and additional neurological disorders, as well as some specific associated medical conditions. Autism with regression has been reported in one-third of children with previously normal or nearly normal development. In an unknown proportion of these subjects, epileptic disorders are concomitant, leading to so-called autistic epileptiform regression. Furthermore, epileptiform abnormalities without seizures are frequent in this population and their role in the development of the nuclear disturbances of autism is controversial. The therapeutic approaches to epilepsy in autism are conventional treatments, yet when seizures are not evident, there is still controversy. Anticonvulsant medications could also potentially interfere with mood and behavioral disturbances frequently observed in ASD. The current understanding of the association between epilepsy and autism is still limited, but from a clinical point of view this association should not be overlooked, and it should be routinely investigated.

Adolescent↗

PubMed2005

Clinical experience with Topiramate to counteract neuroleptic induced weight gain in 10 individuals with autistic spectrum disorders.

Children and adolescents with autistic spectrum disorders are treated with neuroleptics to limit behavioral disturbances such as aggression, hyperactivity and self-injury. They may experience substantial weight gain when undergoing treatment with atypical antipsychotics actually employed. Topiramate (TPM) is an antiepileptic medication that is being progressively demonstrating a wider spectrum of action, mainly as an agent for weight control and as a mood stabilizer. It was administered to a group of children and adolescents with autistic spectrum disorders with the aim of reversing weight gain. This is an open study over an observation period of 18 months of 10 children and adolescents, eight males and two females, mean age 13 years, SD+/-3.6, range 8-19 years with a diagnosis of autistic disorder or pervasive developmental disorder not otherwise specified according to DSM-IV. Starting dosage of TPM was 0.5 mg/kg followed by titration of 0.5 mg/kg on a weekly basis, up to 1-3 mg/kg/day as the maintenance dosage. Eight subjects were undergoing long-term treatment with risperidone, one with pimozide and one was temporarily not on antipsychotics. Six patients took TPM on a regular basis and four dropped out. Variable degrees of weight reduction were observed in four patients, two subjects showed weight increase. Behavioral adverse effects were observed in three patients causing rapid withdrawal of the medication. TPM should be used with caution in autistic spectrum disorders because this population has a high risk of behavioral disruption.

Adolescent↗

PubMed2005

Epilepsy, electroencephalographic abnormalities, and regression in children with autism.

The association of epilepsy and autism is recognized, and it has been reported at a percentage that varies between 8 and 42%, depending on age and diagnostic criteria. One third of autistic children undergo a regression of language and behavior between 2 and 3 years, and epileptiform abnormalities and epilepsy can be concomitant in an undetermined percentage of them. The aim of this study was to investigate the prevalence of epilepsy and paroxysmal abnormalities in a group of children with autism and to determine the percentage of regression course in this group. Forty-six patients with autism (mean age 7.8 +/- 2.7 years; 34 boys and 12 girls) were consecutively examined, and clinical evaluation, assessment, and electroencephalographic (EEG) recordings were performed in all of them. Thirty-five percent showed paroxysmal abnormalities and epilepsy, 22% had only paroxysmal abnormalities without seizures, and 13% of the children suffered from epilepsy. Sixty-five percent had a normal EEG. No difference in regression rate was observed between patients with paroxysmal abnormalities and epilepsy and those with a normal EEG and without seizures. In the study group, the prevalence of epilepsy was in the low range of individuals with autism, and different types of epilepsy were observed. Autism with regression was not influenced by paroxysmal abnormalities and epilepsy.

Autistic Disorder↗

PubMed2004

Three Rett patients with both MECP2 mutation and 15q11-13 rearrangements.

Autism and Rett syndrome, a severe neurological disorder with autistic behavior, are classified as separate disorders on clinical and etiological ground. Rett syndrome is a monogenic X-linked dominant condition due to de novo mutations in the MECP2 gene, whereas autism is a neurodevelopmental and behavioral disorder with complex genetic basis. Maternally inherited duplications on 15q11-q13 are found in a fraction of autistic children suggesting that an abnormal dosage of gene(s) within this region might cause susceptibility to autism. Now we show that three Rett patients are carriers of both a MECP2 mutation and a 15q11-q13 rearrangement, suggesting that there might be a relationship between autism-related genes and the MECP2 gene.

Chromosomal Proteins, Non-Histone↗

PubMed2003

Study of MECP2 gene in Rett syndrome variants and autistic girls.

Mutations in MECP2 gene account for approximately 80% of cases of Rett syndrome (RTT), an X-linked severe developmental disorder affecting young girls, as well as for most cases of Preserved Speech Variant (PSV), a mild RTT variant in which autistic behavior is common. The aim of this study is to determine whether MECP2 mutations are responsible for PSV only or may cause other forms of autistic disorders. We screened for mutations by SSCP 19 girls with a clinical diagnosis of autism, two of them fulfilling the PSV criteria. A pathogenic mutation was found only in the latter two cases (R133C and R453X). A long follow-up of these two girls revealed a unique clinical course. They initially developed the first three stages of RTT, they were severely retarded and had autistic behavior. Over the years their abilities increased progressively and by early adolescence they lost autistic behavior, becoming adequately accustomed to people and reaching an IQ close to 45. These results confirm previous clinical studies suggesting that a wide spectrum of RTT exists including girls with mental abilities considerably higher than in classic RTT. We conclude that MECP2 mutations (missense or late truncating) can be found in girls with an IQ close to 45 and a clinical history of PSV of Rett syndrome. Furthermore, MECP2 mutations are not found in patients in which autism remains stable over the years.

Adolescent↗

PubMedDate not supplied

Autistic epileptiform regression.

Autistic regression is a well known condition that occurs in one third of children with pervasive developmental disorders, who, after normal development in the first year of life, undergo a global regression during the second year that encompasses language, social skills and play. In a portion of these subjects, epileptiform abnormalities are present with or without seizures, resembling, in some respects, other epileptiform regressions of language and behaviour such as Landau-Kleffner syndrome. In these cases, for a more accurate definition of the clinical entity, the term autistic epileptifom regression has been suggested. As in other epileptic syndromes with regression, the relationships between EEG abnormalities, language and behaviour, in autism, are still unclear. We describe two cases of autistic epileptiform regression selected from a larger group of children with autistic spectrum disorders, with the aim of discussing the clinical features of the condition, the therapeutic approach and the outcome.

Anticonvulsants↗