Phocomelia: A worldwide descriptive epidemiologic study in a large series of cases from the International Clearinghouse for Birth Defects Surveillance and Research, and overview of the literature

Abstract

Epidemiologic data on phocomelia are scarce. This study presents an epidemiologic analysis of the largest series of phocomelia cases known to date. Data were provided by 19 birth defect surveillance programs, all members of the International Clearinghouse for Birth Defects Surveillance and Research. Depending on the program, data corresponded to a period from 1968 through 2006. A total of 22,740,933 live births, stillbirths and, for some programs, elective terminations of pregnancy for fetal anomaly (ETOPFA) were monitored. After a detailed review of clinical data, only true phocomelia cases were included. Descriptive data are presented and additional analyses compared isolated cases with those with multiple congenital anomalies (MCA), excluding syndromes. We also briefly compared congenital anomalies associated with nonsyndromic phocomelia with those presented with amelia, another rare severe congenital limb defect. A total of 141 phocomelia cases registered gave an overall total prevalence of 0.62 per 100,000 births (95% confidence interval: 0.52-0.73). Three programs (Australia Victoria, South America ECLAMC, Italy North East) had significantly different prevalence estimates. Most cases (53.2%) had isolated phocomelia, while 9.9% had syndromes. Most nonsyndromic cases were monomelic (55.9%), with an excess of left (64.9%) and upper limb (64.9%) involvement. Most nonsyndromic cases (66.9%) were live births; most isolated cases (57.9%) weighed more than 2,499 g; most MCA (60.7%) weighed less than 2,500 g, and were more likely stillbirths (30.8%) or ETOPFA (15.4%) than isolated cases. The most common associated defects were musculoskeletal, cardiac, and intestinal. Epidemiological differences between phocomelia and amelia highlighted possible differences in their causes.

Amelia: A multi‐center descriptive epidemiologic study in a large dataset from the International Clearinghouse for Birth Defects Surveillance and Research, and overview of the literature

“…Some influence the initiation and patterning of both the forelimb and the hindlimb, but others are differentially expressed in the developing forelimb and hindlimb. In Table I, the main genes or gene families involved in limb development are summarized, and other details are provided by Bermejo‐Sánchez et al [in press] in this issue of the journal. Apart from the action of these genetic factors, retinoic acid (RA) levels must be carefully controlled during limb bud development since both high and low levels have been associated with developmental abnormalities.…”

“…Data on the prevalence of amelia are scarce, and most published articles on this congenital defect are single case reports or limited series. Moreover, in some studies cases of amelia were not analyzed separately from other transverse limb reduction defects or from phocomelia (which is characterized by the absence of the intermediate segments of the limb with the distal segments being present, and is reviewed in this issue of the journal [Bermejo‐Sánchez et al, in press]). As can be observed from the few published studies providing data on this condition (Table III), amelia has a low prevalence ranging from 0.95 per 100,000 births [Källén et al, 1984] to 1.71 per 100,000 births [Castilla et al, 1995].…”

Achieving the targets of sustainable development goals (2030 agenda) for congenital disorders in Asia: Bottlenecks and interventions

“…Many health authorities recognized the need for a national birth defects or congenital disorders registry in their respective countries (Gupta, Kabra, & Kapoor, ; Padilla, Cutiongco, & Sia, ). Some countries published specific birth defects (Bermejo‐Sánchez et al, ; Shapira, Hakla, Blum, Shpack, & Amitai, ) or pilot studies (Hoang et al, ). In the Republic of Korea, data were obtained from a pilot study based on the medical insurance claims database of the National Health Insurance Corporation and the conclusion, there was a need to establish a registry system of birth defects in Korea (Kim, Yee, Choi, Choi, & Seo, ) The international clearinghouse for birth defects surveillance and research (ICBDSR) was established in 1974 and published annual global epidemiological data on birth defects from 42 surveillance programs originating from 36 countries.…”

Epidemiological Association of Cannabinoid- and Drug- Exposures and Sociodemographic Factors with Limb Reduction Defects Across USA 1989-2016: A Geotemporospatial and Causal Inference Study

“…Limb reductions (LR) are rare and dramatic defects which were first described several thousand years ago in the literature of antiquity (Bermejo-Sanchez, Cuevas et al 2011, Bermejo-Sanchez, Cuevas et al 2011). More recently they received prominence as the hallmark and initial indication of the teratogenic action of the drug thalidomide (Bermejo-Sanchez, Cuevas et al 2011, Bermejo-Sanchez, Cuevas et al 2011). LR includes both absence of proximal limb elements (intercalary segments, phocomelia) as well as complete limb absence limbs (amelia).…”

“…Given CDC data indicate 3,791,715 US births in 2018 this suggests over 1,600 LR cases annually (CDC, Centers for Disease Control et al 2019). Leading studies from the International Clearing House of Birth Defects Surveillance and Research (ICBDSR) noted that little was known about the causes of these disorders (Bermejo-Sanchez, Cuevas et al 2011, Bermejo-Sanchez, Cuevas et al 2011). Sometimes LR arise as part of exceedingly rare congenital syndromes or together with multiple congenital anomalies, however their most common presentation is as an isolated disorder.…”