Birth prevalence of achondroplasia: A systematic literature review and meta‐analysis

Abstract

Achondroplasia is a genetic disorder that results in disproportionate short stature. The true prevalence of achondroplasia is unknown as estimates vary widely. This systematic literature review and meta‐analysis was conducted to better estimate worldwide achondroplasia birth prevalence. PubMed, Embase, Scielo, and Google Scholar were searched, complemented by manual searching, for peer‐reviewed articles published between 1950 and 2019. Eligible articles were identified by two independent researchers using predefined selection criteria. Birth prevalence estimates were extracted for analysis, and the quality of evidence was assessed. A meta‐analysis using a quality effects approach based on the inverse variance fixed effect model was conducted. The search identified 955 unique articles, of which 52 were eligible and included. Based on the meta‐analysis, the worldwide birth prevalence of achondroplasia was estimated to be 4.6 per 100,000. Substantial regional variation was observed with a considerably higher birth prevalence reported in North Africa and the Middle East compared to other regions, particularly Europe and the Americas. Higher birth prevalence was also reported in specialized care settings. Significant heterogeneity (Higgins I2 of 84.3) was present and some indication of publication bias was detected, based on visual asymmetry of the Doi plot with a Furuya‐Kanamori index of 2.73. Analysis of pooled data from the current literature yields a worldwide achondroplasia birth prevalence of approximately 4.6 per 100,000, with considerable regional variation. Careful interpretation of these findings is advised as included studies are of broadly varying methodological quality.

Childhood prevalence of achondroplasia in New South Wales and the Australian Capital Territory, Australia

“…This report provides new achondroplasia birth prevalence and childhood prevalence data for NSW, Australia's most populous state, and the ACT, which together include 33% of the Australian population (ABS, 2020a). The birth prevalence rate of 5.3 per 100,000 in the decade 2010–2019 in our study is slightly higher compared with the earlier published estimates for Australian populations of 3.86 and 4.93 per 100,000, respectively (Källén et al, 1993; Oberklaid et al, 1979), and the worldwide rate of 4.6 per 100,000 from a recent meta‐analysis (Foreman et al, 2020). The birth prevalence rate of 5.3 per 100,000 and the childhood prevalence rate of 5.2 per 100,000 were similar in our study, despite some population mobility with individuals migrating in and out of the NSW/ACT area.…”

“…Achondroplasia is the most common skeletal dysplasia, with an estimated worldwide birth prevalence of 4.6 per 100,000 (Foreman et al, 2020). The achondroplasia mutation in the gene for fibroblast growth factor receptor 3 (FGFR3) behaves in an autosomal dominant manner, but ~80% of children with achondroplasia are born to parents of average stature and have achondroplasia owing to de novo germ cell mutations (Horton et al, 2007).…”

“…A recent systematic review and meta‐analysis estimated the median birth prevalence of achondroplasia in the geographical region of South and Southeast Asia/Oceania to be 5.9 per 100,000 (Foreman et al, 2020). Included in this estimate were two Australian studies (Källén et al, 1993; Oberklaid et al, 1979).…”

“…In the second study, Kallen et al reported birth data for Australia in 1981–1989 using a national registry of births with congenital malformations, or resulting from in vitro fertilization, including stillbirths after 20 weeks of gestation. From these data, the estimated achondroplasia birth prevalence was 4.93 per 100,000 births but, again, the method of confirming diagnosis was not reported (Foreman et al, 2020).…”

Advantages and Disadvantages of Different Treatment Methods in Achondroplasia: A Review

“…The authors of this review estimated a disease prevalence of 4.6 per 100,000 births, and they noted large regional variation, i.e., higher rates in North Africa and the Middle East than in North America, South America or Europe. However, a limitation of this analysis was the differences in the methodological quality of the compared studies [ 11 ].…”