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.

Figure 1

Clinical photos of some phocomelia cases showing different expressions of the defect. (a), (b-1), (b-2) and (b-3): Two cases with bilateral phocomelia. (c): Unilateral phocomelia, with just some structures of the hand; (d): unilateral phocomelia of the lower limb; (f): see radiologic detail of a case in which different expressions of phocomelia can be observed in the four limbs; (g): only lower limbs involvement. Courtesy of Dr. Salvador Martínez, Dr. Amparo Sanchis, Dr. Consuelo García, Dr. Jaume Rosal, Dr. Manuel Blanco, and Dr. Ignacio Arroyo.

Figure 2

Total prevalence of phocomelia per 100,000 births (bar) and 95% confidence interval (bracketed line) by surveillance program, and overall total prevalence (dotted line), in 19 surveillance programs of the International Clearinghouse for Birth Defects Surveillance and Research.

Figure 3

Prevalence ratios for maternal age groups relative to the reference age of <20 years with corresponding 95% CIs for phocomelia in 17 surveillance programs★ of the International Clearinghouse for Birth Defects Surveillance and Research (syndromic cases excluded). ★Cases and births excluded for the following programs because no births by maternal age were available: China Beijing <1997 and >2003, Germany Saxony– Anhalt <1991, Italy Emilia Romagna <1985, Italy North East, Italy Sicily.