Transient fetal pedal edema as an early sign of 22q11.2 deletion syndrome.

Abstract

We report a case in which a 22q11.2 deletion was diagnosed prenatally in a low-risk pregnancy owing to the finding of transient bilateral pedal edema in the fetus. Microdeletion of chromosome 22q11.2 is the most common deletion syndrome in humans and is associated with a variety of malformations. Particularly common are cardiac defects affecting the outflow tract, found in around 50% of 22q11.2 deletion cases1. Among fetuses with this type of heart defect, 22q11.2 deletion is found in 20% of cases2. Various extracardiac abnormalities are associated with 22q11.2 deletion, as well as significant functional abnormalities, including neurodevelopmental disabilities, immune deficiency and hypocalcemia3. The deletion occurs typically de-novo, but up to 17% of cases are inherited from an affected parent4. The prenatal diagnosis of 22q11.2 deletion has been described since 1997, with fluorescent in-situ hybridization analysis being performed mostly for cases with prenatal detection of a conotruncal heart defect or a family history positive for the deletion1. Many cases with non-cardiac findings possibly go undetected prenatally, as standard cytogenetic testing does not identify this deletion. In the present case, a 29-year-old nulliparous woman attended for routine prenatal ultrasound at 15 weeks' gestation. There were no risk factors for congenital anomalies apart from maternal cleft lip and palate that had been corrected surgically. Transvaginal ultrasound was performed using a Philips IU22 3–10-MHz probe (Bothell, WA, USA). Fetal size was compatible with gestational age. Abnormal sonographic findings in the fetus at 15 weeks included bilateral pedal edema on the dorsal side of the feet (Figure 1 and Videoclip S1), a mildly enlarged, mildly hypokinetic heart with a small pericardial effusion and a persistent left superior vena cava (SVC). The heart structure was otherwise normal. On the follow-up examination at 22 weeks, both the pedal edema and cardiac findings had completely resolved and findings on ultrasound examination were normal except for the persistent left SVC. Amniocentesis was performed and showed normal female karyotype. Further genetic testing, by comparative genomic hybridization analysis, demonstrated a 22q11.2 deletion. The pregnancy was terminated at the request of the parents. In this case, 22q11.2 deletion was diagnosed prenatally based on the observation of transient pedal edema without the presence of a major heart defect. It was an independent finding and unlikely to be related to the mildly hypokinetic heart since other signs of heart failure were absent. Pedal edema in the fetus is an unusual finding. Differential diagnosis includes Turner syndrome, non-lymphatic edema and several hereditary lymphedema syndromes such as lymphedema–distichiasis syndrome, lymphedema and ptosis syndrome, Milroy's primary congenital lymphedema, hereditary lymphedema Type II and congenital recessive type lymphedema5. In our case, resolution of the edema in combination with a normal fetal karyotype excluded these syndromes. Interestingly, the phenomenon of early and transient pedal edema described in the current case resembles the phenomenon of early and transient nuchal edema, a well-established marker for major chromosomal abnormalities, yet the pathogenesis of both is unclear. In conclusion, our finding suggests that 22q11.2 deletion may be included in the differential diagnosis of pedal edema in the fetus. A. Gover*†, A. Rotschild†‡ and M. Bronshtein§ †Carmel Medical Center, Haifa, Israel; ‡The Ruth & Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel; §Faculty of Social Welfare and Health Science, Haifa University, Haifa, Israel *Correspondence. (e-mail: [email protected]) Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.