Fetal upper limb amelia with increased nuchal translucency

Embryogenesis of the upper extremity commences four weeks after fertilization, with formation of the upper limb bud on the lateral wall of the embryo, and ends at eight weeks of gestation. In animal models three signaling centers of limb development have been discovered. The apical ectodermal ridge is obligated for limb development in a proximal-to-distal direction. The zone of polarizing activity functions as a signaling center for anterior-to-posterior (radioulnar) limb development. The Wnt signaling center resides in the dorsal ectoderm and secretes factors that induce the underlying mesoderm to adopt dorsal-to-ventral axis configuration. Abnormalities within one signaling center indirectly prohibit adequate functioning of the other two remaining centers and affect limb formation (Bamshad et al. 1999). Amelia, the absence of upper and/or lower limbs, represents a longitudinal failure of formation with an absent intervening segment of the extremity (intercalary aplasia). Amelia may be unilateral or bilateral, with different levels of severity in relationship with embryogenesis disruption and may present as an isolated or associated finding, often inherited as part of a genetic syndrome. The isolated form is often sporadic, moreover an autosomal recessive inheritance (OMIM 601360) was supposed by Michaud et al. (1995). Nuchal translucency (NT) is defined as a measurement of the size of the translucent space behind the neck of the fetus using ultrasound between 10 and 14 weeks of pregnancy, reflecting the amount of fluid that has accumulated under the skin of the fetus. Increased NT is associated with an increased risk of chromosomal abnormality and is a marker for major cardiac defects, non-cardiac structural defects, and rare genetic syndromes, including skeletal dysplasias in chromosomally normal fetuses (Snijders et al. 1998; Hyett et al. 1999). The association between upper limb amelia and increased NT has been reported only by Souter et al. (2002) in a case of monochorionic, diamniotic twin pregnancy. The patient was referred to us at 13 weeks of gestation in her first pregnancy. There was no history of teratological exposure or family genetic condition; maternal age was 35 years and paternal age was 40. Ultrasonographic evaluation with 2D and 4D demonstrated an NT value of 3 mm and upper limb amelia (Fig. 1). Fetal karyotype was 46,XY. After genetic counseling the couple decided to perform voluntary termination of pregnancy. Fetal examination and X-ray confirmed the upper limb amelia (Fig. 2) without additional anomalies at fetal autopsy. 2D and 4D ultrasonography with evidence of upper limb amelia and increased nuchal translucency. Fetal (A) lateral and (B) frontal appearance with evidence of upper limb amelia and nuchal neck. (C) Fetal X-ray. The pathophysiological mechanisms of increased NT are not clear and may vary with the underlying condition. These include over-expression of collagen VI and increased hyaluronan in the skin of fetuses with trisomy 21 (Von Kaisenberg et al. 1998; Bohlandt et al. 2000). Mediastinal compression due to narrowing of the fetal chest and alterations in the composition of the dermis have been postulated as possible causes of increased NT in fetuses with skeletal dysplasias (Makrydimas et al. 2001). Moreover pathophysiological mechanisms underlying increased NT in the presence of upper limb phocomelia are not clear. In conclusion, the present case adds to the body of literature supporting an association between increased NT and skeletal abnormalities. It also serves as a reminder of the value of looking for fetal structural abnormalities on sonography when increased NT is detected in the first trimester of pregnancy.