Abstract
BackgroundTo review the descriptive epidemiological data on neuronal ceroid lipofuscinoses (NCLs) in Italy, identify the spectrum of mutations in the causative genes, and analyze possible genotype-phenotype relations.MethodsA cohort of NCL patients was recruited through CLNet, a nationwide network of child neurology units. Diagnosis was based on clinical and pathological criteria following ultrastructural investigation of peripheral tissues. Molecular confirmation was obtained during the diagnostic procedure or, when possible, retrospectively.ResultsOne hundred eighty-three NCL patients from 156 families were recruited between 1966 and 2010; 124 of these patients (from 88 families) were tested for known NCL genes, with 9.7% of the patients in this sample having not a genetic diagnosis. Late infantile onset NCL (LINCL) accounted for 75.8% of molecularly confirmed cases, the most frequent form being secondary to mutations in CLN2 (23.5%). Juvenile onset NCL patients accounted for 17.7% of this cohort, a smaller proportion than found in other European countries. Gene mutations predicted severe protein alterations in 65.5% of the CLN2 and 78.6% of the CLN7 cases. An incidence rate of 0.98/100,000 live births was found in 69 NCL patients born between 1992 and 2004, predicting 5 new cases a year. Prevalence was 1.2/1,000,000.ConclusionsDescriptive epidemiology data indicate a lower incidence of NCLs in Italy as compared to other European countries. A relatively high number of private mutations affecting all NCL genes might explain the genetic heterogeneity. Specific gene mutations were associated with severe clinical courses in selected NCL forms only.
Highlights
To review the descriptive epidemiological data on neuronal ceroid lipofuscinoses (NCLs) in Italy, identify the spectrum of mutations in the causative genes, and analyze possible genotype-phenotype relations
We investigated the frequency of childhood-onset NCLs in Italy, examining clinical and molecular data collected mainly through a collaborative network (CLNet) of paediatric neurology units applying common diagnostic protocols
Descriptive epidemiology One hundred eighty-three patients with childhood-onset NCL, born between 1966 and 2010 and belonging to 156 families were identified in the CLNet database
Summary
To review the descriptive epidemiological data on neuronal ceroid lipofuscinoses (NCLs) in Italy, identify the spectrum of mutations in the causative genes, and analyze possible genotype-phenotype relations. The neuronal ceroid lipofuscinoses (NCLs) are the most common group of inherited, progressive neurodegenerative diseases of childhood, which are secondary to abnormal intralysosomal storage of autofluorescent material and show specific ultrastructural features. Over the past 10 years, routine use of molecular genetics to corroborate clinical diagnoses has made it possible to obtain more accurate epidemiological data on the NCLs, which have been shown to have a worldwide distribution [14]. We investigated the frequency of childhood-onset NCLs in Italy, examining clinical and molecular data collected mainly through a collaborative network (CLNet) of paediatric neurology units applying common diagnostic protocols
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