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. 2013 Feb 2:8:19.
doi: 10.1186/1750-1172-8-19.

Molecular epidemiology of childhood neuronal ceroid-lipofuscinosis in Italy

Filippo Maria Santorelli  1 , Barbara Garavaglia, Francesco Cardona, Nardo Nardocci, Bernardo Dalla Bernardina, Stefano Sartori, Agnese Suppiej, Enrico Bertini, Dianela Claps, Roberta Battini, Roberta Biancheri, Mirella Filocamo, Francesco Pezzini, Alessandro Simonati
Affiliations

Molecular epidemiology of childhood neuronal ceroid-lipofuscinosis in Italy

Filippo Maria Santorelli et al. Orphanet J Rare Dis. .

Abstract

Background: 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.

Methods: A 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.

Results: One 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.

Conclusions: Descriptive 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.

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Figures

Figure 1
Figure 1
Plotting of cumulative index of 183 NCL cases born in 1966–2010 as ascertained by CLNet. Patients are sorted by year of birth and plotted by number of new cases per year (dark dots) and cumulative number of cases. The curve shows relatively steady recruitment of new cases over time, with a slight deflection from the mid-1980s to the mid-1990’s (circled). The flat ends of the curve are possibly related to under-diagnosis during the late-1960s to early-1970s, and the presence of still undiagnosed cases today (right end of the curve).
See this image and copyright information in PMC

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