A retrospective analysis of the prevalence of imprinting disorders in Estonia from 1998 to 2016

Abstract

Imprinting disorders (ImpDis) represent a small group of rare congenital diseases primarily affecting growth, development, and the hormonal and metabolic systems. The aim of present study was to identify the prevalence of the ImpDis in Estonia, to describe trends in the live birth prevalence of these disorders between 1998 and 2016, and to compare the results with previously published data. We retrospectively reviewed the records of all Estonian patients since 1998 with both molecularly and clinically diagnosed ImpDis. A prospective study was also conducted, in which all patients with clinical suspicion for an ImpDis were molecularly analyzed. Eighty-seven individuals with ImpDis were identified. Twenty-seven (31%) of them had Prader-Willi syndrome (PWS), 15 (17%) had Angelman syndrome (AS), 15 (17%) had Silver-Russell syndrome (SRS), 12 (14%) had Beckwith-Wiedemann syndrome (BWS), 10 (11%) had pseudo- or pseudopseudohypoparathyroidism, four had central precocious puberty, two had Temple syndrome, one had transient neonatal diabetes mellitus, and one had myoclonus-dystonia syndrome. One third of SRS and BWS cases fulfilled the diagnostic criteria for these disorders, but tested negative for genetic abnormalities. Seventy-six individuals were alive as of January 1, 2018, indicating the total prevalence of ImpDis in Estonia is 5.8/100,000 (95% CI 4.6/100,000-7.2/100,000). The minimum live birth prevalence of all ImpDis in Estonia in 2004-2016 was 1/3,462, PWS 1/13,599, AS 1/27,198, BWS 1/21,154, SRS 1/15,866, and PHP/PPHP 1/27,198. Our results are only partially consistent with previously published data. The worldwide prevalence of SRS and GNAS-gene-related ImpDis is likely underestimated and may be at least three times higher than expected.

Fig. 1

Pie charts showing the percentage of all molecularly and clinically diagnosed ImpDis in Estonia during the periods 1998-2016, 1998-2017, and 1998-2018. Note the important increase in percentage of rare ImpDis (TS14, PHP/PPHP, TNDM, CPP, MDS) during the past few years

Fig. 2

Distribution of live birth prevalence of all ImpDis (a), PWS (b), AS (c), BWS (d), SRS (e), and PHP/PPHP (f) in Estonia from 1998 to 2016 by statistical logit analysis. The solid line represents birth prevalence and the dashed lines the 95% confidence interval. Note a statistically significant increase in the live birth prevalence of all ImpDis (P = 0.027) and BWS (P = 0.0206). There was no statistically significant increase in the live birth prevalence of PWS (P = 0.9806), AS (P = 0.5331), SRS (P = 0.1851), and PHP/PPHP (P = 0.7792) during this period