Amelia, Autosomal Recessive

Clinical Features

Michaud et al. (1995) described a French Canadian family in which 3 fetuses of both sexes had amelia of the upper limbs with severe underdevelopment of the lower limbs. In the first fetus, absence of both upper limbs and the right lower limb was associated with short femur on the left side. No visceral defects were found on autopsy. The second fetus showed amelia of the upper limbs and a single severely hypoplastic femur. The third fetus had amelia of the upper limbs and terminal transverse deficiency of the lower limbs. Autopsy was not possible in the last 2 cases. The authors noted that recurrent amelia has been documented in only a few families and has most often been associated with a different set of malformations.

Bermejo-Sanchez et al. (2011) reported that the most frequent defects associated with amelia were other types of musculoskeletal defects, intestinal defects, some renal and genital defects, oral clefts, defects of cardiac septa, and anencephaly.

Inheritance

Michaud et al. (1995) suggested that amelia in the French Canadian family they described was inherited in an autosomal recessive manner.

Population Genetics

Bermejo-Sanchez et al. (2011) described the epidemiology of congenital amelia using data gathered from 20 surveillance programs on congenital anomalies, all International Clearinghouse for Birth Defects Surveillance and Research members, from all continents but Africa, from 1968 to 2006, depending on the program. Reported clinical information on cases was thoroughly reviewed to identify those strictly meeting the definition of amelia. Those with amniotic bands or limb-body wall complex were excluded. The primary epidemiologic analyses focused on isolated cases (about one-third) and those with multiple congenital anomalies (MCA) (two-thirds). A total of 326 amelia cases were ascertained among 23,110,591 live births, stillbirths, and, for some programs, elective terminations of pregnancy for fetal anomalies. The overall total prevalence was 1.41 per 100,000 (95% confidence interval 1.26-1.57). Only China, Beijing, and Mexico RYVEMCE had total prevalences, which were significantly higher than this overall total prevalence. Some underregistration could have influenced the total prevalence in some programs. Liveborn cases represented 54.6% of the total. Among monomelic cases (representing 65.2% of nonsyndromic amelia cases), both sides were equally involved, and the upper limbs (53.9%) were slightly more frequently affected. One of the most interesting findings was a higher prevalence of amelia among offspring of mothers younger than 20 years. Sixty-nine percent of the cases had MCA or syndromes.