11 research outputs found
Tubulin-related cerebellar dysplasia: definition of a distinct pattern of cerebellar malformation
none25siTo determine the neuroimaging pattern of cerebellar dysplasia (CD) and other posterior fossa morphological anomalies associated with mutations in tubulin genes and to perform clinical and genetic correlations.Erratum to: Tubulin-related cerebellar dysplasia: definition of a distinct pattern of cerebellar malformation. [Eur Radiol. 2017]Romaniello, Romina; Arrigoni, Filippo; Panzeri, Elena; Poretti, Andrea; Micalizzi, Alessia; Citterio, Andrea; Bedeschi, Maria Francesca; Berardinelli, Angela; Cusmai, Raffaella; D'Arrigo, Stefano; Ferraris, Alessandro; Hackenberg, Annette; Kuechler, Alma; Mancardi, Margherita; Nuovo, Sara; Oehl-Jaschkowitz, Barbara; Rossi, Andrea; Signorini, Sabrina; Tüttelmann, Frank; Wahl, Dagmar; Hehr, Ute; Boltshauser, Eugen; Bassi, Maria Teresa; Valente, Enza Maria; Borgatti, RenatoRomaniello, Romina; Arrigoni, Filippo; Panzeri, Elena; Poretti, Andrea; Micalizzi, Alessia; Citterio, Andrea; Bedeschi, Maria Francesca; Berardinelli, ANGELA LUCIA; Cusmai, Raffaella; D'Arrigo, Stefano; Ferraris, Alessandro; Hackenberg, Annette; Kuechler, Alma; Mancardi, Margherita; Nuovo, Sara; Oehl Jaschkowitz, Barbara; Rossi, Andrea; Signorini, SABRINA GIOVANNA; Tüttelmann, Frank; Wahl, Dagmar; Hehr, Ute; Boltshauser, Eugen; Bassi, Maria Teresa; Valente, ENZA MARIA; Borgatti, Renat
Early immunotherapy and longer corticosteroid treatment are associated with lower risk of relapsing disease course in pediatric MOGAD
Background and objectives: We sought to identify early factors associated with relapse and outcome in paediatric-onset myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD). Methods: In a multicenter retrospective cohort of pediatric MOGAD (≤18 years), onset features and treatment were compared in patients with monophasic vs relapsing disease (including cases with follow-up ≥12 months after onset or relapse at any time) and in patients with final Expanded Disability Status Scale (EDSS) 0 vs ≥1 at last follow-up (including cases with follow-up >3 months after last event or EDSS0 at any time). Multivariable logistic regression models were used to evaluate factors associated with relapsing disease course and EDSS ≥ 1 at final follow-up. Results: Seventy-five children were included (median onset age 7 years; median 30 months of follow-up). Presentation with acute disseminated encephalomyelitis was more frequent in children aged 8 years or younger (66.7%, 28/42) than in older patients (30.3%, 10/33) (p = 0.002), whereas presentation with optic neuritis was more common in children older than 8 years (57.6%, 19/33) than in younger patients (21.4%, 9/42) (p = 0.001). 40.0% (26/65) of patients relapsed. Time to first relapse was longer in children aged 8 years or younger than in older patients (median 18 vs 4 months) (p = 0.013). Factors at first event independently associated with lower risk of relapsing disease course were immunotherapy <7 days from onset (6.7-fold reduced odds of relapsing course, OR 0.15, 95% CI 0.03-0.61, p = 0.009), corticosteroid treatment for ≥5 weeks (6.7-fold reduced odds of relapse, OR 0.15, 95% CI 0.03-0.80, p = 0.026), and abnormal optic nerves on onset MRI (12.5-fold reduced odds of relapse, OR 0.08, 95% CI 0.01-0.50, p = 0.007). 21.1% (15/71) had EDSS ≥ 1 at final follow-up. Patients with a relapsing course had a higher proportion of final EDSS ≥ 1 (37.5%, 9/24) than children with monophasic disease (12.8%, 5/39) (p = 0.022, univariate analysis). Each 1-point increment in worst EDSS at onset was independently associated with 6.7-fold increased odds of final EDSS ≥ 1 (OR 6.65, 95% CI 1.33-33.26, p = 0.021). Discussion: At first attack of pediatric MOGAD, early immunotherapy, longer duration of corticosteroid treatment, and abnormal optic nerves on MRI seem associated with lower risk of relapse, whereas higher disease severity is associated with greater risk of final disability (EDSS ≥ 1)
Tubulin-related cerebellar dysplasia: definition of a distinct pattern of cerebellar malformation
Corpus callosum abnormalities: neuroimaging, cytogenetics and clinical characterization of a very large multicenter Italian series
Corpus callosum abnormalities (CCA) have an estimated prevalence
ranging from 0.3% up to 0.7% in patients undergoing brain imaging.
CCA can be identified incidentally, or can be part of a developmental
disease. We performed a retrospective study of 551 patients, identified
non-syndromic (NS) CCA and syndromic (S) CCA, reviewing clinical features,
neuroradiological aspects, genetic etiology, and chromosomal
microarray (CMA) results. Syndromic CCA subjects were prevalent
(60%) and they showed the most severe clinical features. Cortical malformations
and cerebellar anomalies were 23% of cerebral malformation
associated to CCA (plus), 23 and 14% respectively in syndromic forms. A clinical and/or genetic diagnosis was obtained in 37% of
syndromic CCA including chromosomal rearrangements on high-resolution
karyotype (18%), microdeletion/microduplication syndromes
(31%) and monogenic diseases (51%). Non-syndromic CCA anomalies
had mildest clinical features, although intellectual disability was present
in 49% of cases and epilepsy in 13%. CMA diagnostic rate in our
cohort of patients ranged from 11 to 23% (NS to S). A high percentage
of patients (76% 422/551) remain without a diagnosis. Combined high
resolution CMA studies and next-generation sequencing (NGS) strategies
will increase the probability to identify new causative genes of
CCA and to redefine genotype–phenotype correlation
Age and sex prevalence estimate of Joubert syndrome in Italy
ObjectiveTo estimate the prevalence of Joubert syndrome (JS) in Italy applying standards of descriptive epidemiology and to provide a molecular characterization of the described patient cohort.MethodsWe enrolled all patients with a neuroradiologically confirmed diagnosis of JS who resided in Italy in 2018 and calculated age and sex prevalence, assuming a Poisson distribution. We also investigated the correlation between proband chronological age and age at diagnosis and performed next-generation sequencing (NGS) analysis on probands' DNA when available.ResultsWe identified 284 patients with JS: the overall, female- and male-specific population-based prevalence rates were 0.47 (95% confidence interval [CI] 0.41-0.53), 0.41 (95% CI 0.32-0.49), and 0.53 (95% CI 0.45-0.61) per 100,000 population, respectively. When we considered only patients in the age range from 0 to 19 years, the corresponding population-based prevalence rates rose to 1.7 (95% CI 1.49-1.97), 1.62 (95% CI 1.31-1.99), and 1.80 (95% CI 1.49-2.18) per 100,000 population. NGS analysis allowed identifying the genetic cause in 131 of 219 screened probands. Age at diagnosis was available for 223 probands, with a mean of 6.67 8.10 years, and showed a statistically significant linear relationship with chronological age (r(2) = 0.79; p < 0.001).ConclusionsWe estimated for the first time the age and sex prevalence of JS in Italy and investigated the patients' genetic profile. The obtained population-based prevalence rate was 10 times higher than that available in literature for children population