Trisomy 9 presenting in the first trimester as a fetal lateral neck cyst and increased nuchal translucency

Introduction

Fetal lateral neck cysts are transient fluid accumulations that result from abnormal lymphatic formations. In the first trimester, fetal lateral neck cysts accompanied by an increased nuchal translucency have been associated with aneuploidy, single-gene disorders and other malformations [1], [2], [3], [4], [5]. We describe a case in which a lateral neck cyst was detected by ultrasonography in the first trimester with the additional finding of increased nuchal translucency in a fetus with trisomy 9. This report illustrates the importance of identifying additional abnormalities in a fetus with lateral neck cysts, documenting the size of the cysts, and obtaining diagnostic genetic testing.

Presentation of the case

A 33-year-old multiparous woman was referred for first trimester nuchal translucency screening at 12 weeks’ gestation. Fetal biometry was consistent with menstrual dates. The nuchal translucency measured 3.7 mm (>95^th percentile) and there was a 6.7 × 4 × 6.2 mm cyst in the right anterior lateral neck (Figure 1A–C). No other abnormalities were detected at that time. Standard cell-free (cf) DNA screening had been obtained by the referring physician prior to the ultrasound, with no aneuploidy detected for chromosomes 21, 18, 13 and the sex chromosomes. The patient declined diagnostic testing with chorionic villus sampling (CVS).

Figure 1:

Right lateral neck cyst in a fetus with trisomy 9.

(A) Sagittal transvaginal sonogram showing the fetal neck cyst. (B) Transverse transvaginal sonogram showing a cystic area in the right lateral aspect of the fetal neck. (C) Sagittal transvaginal ultrasound showing an enlarged nuchal translucency.

A repeat ultrasound at 16 weeks’ gestation demonstrated a normally grown fetus with persistence of the cyst, which measured 4.9 × 5 × 8.4 mm, as well as a pericardial effusion with a single outflow tract overriding the ventricular septum and vermian hypoplasia. The diagnosis of trisomy 9, 47,XX,+9, was made by amniocentesis and the patient opted for termination of the pregnancy. An autopsy was not performed.

Discussion

Fetal lateral neck cysts are transient fluid-filled structures thought to arise from delayed communication between fetal lymphatic sacs and the developing venous system. The reported incidence of fetal lateral neck cysts is 0.76–2.8% [1], [5]. They are also referred to as “anterolateral neck cysts” and “non-septated cystic hygromas” in the literature. They are distinguished from posterior neck cysts and septated cystic hygromas, which differ in location, morphology, and prognosis [6].

Fetal lateral neck cysts can be detected during the first and early-second trimesters and exist in association with chromosomal aneuploidies, single-gene disorders, familial disorders and other malformations. Specifically, they have been reported with trisomies 13, 18, and 21, monosomy XO, Robertsonian translocation [46,XX, t(14;21)] and 47,+ del(21)(q22.1) [1], [2], [3], [4], [5]. However, this association with genetic abnormalities has been described when the fetal lateral neck cysts are accompanied by an increased nuchal translucency [1], [3], [5]. Rarely, lateral neck cysts in the absence of an increased nuchal translucency or other malformations have been reported to have a chromosomal abnormality [7].

We queried PubMed for cases of a fetal lateral neck cyst associated with trisomy 9 using the Mesh terms “neck/embryology”, “chromosome disorders/diagnostic imaging”, “trisomy/diagnosis”, “ultrasonography, prenatal,” cysts/congenital” and “cysts/diagnostic imaging.” Non-English language journals were excluded from our search. Our review of the literature failed to identify any cases of a fetal lateral neck cyst associated with trisomy 9. Trisomy 9, without evidence of mosaicism, is a rare chromosomal abnormality that usually results in spontaneous abortion. Reported cases diagnosed after the first trimester describe various sonographic abnormalities, the most common ones being intracranial and cardiac [8]. Additional findings include abnormalities of the urinary system, extremities (rocker-bottom feet, clenched hands) and head [8].

Several authors [1], [3], [5] have reported that the finding of an isolated lateral neck cyst in the first and early second trimester is not associated with an increased aneuploidy risk or structural abnormalities. On the other hand, in the presence of an increased nuchal translucency, Achiron et al. [1] reported a 25% incidence of aneuploidy. In 2016, Meyberg-Solomayer et al. [5] reported that 65% of the fetuses were aneuploid, and 85% had an aneuploidy or a structural abnormality. Interestingly, fetuses with cysts smaller than 3 mm had a normal outcome regardless of nuchal translucency measurement [5]. Our patient had a lateral neck cyst much greater than 3 mm.

Once a fetal lateral neck cyst is detected, especially with an additional abnormality such as increased nuchal translucency, invasive testing with either CVS or amniocentesis for karyotype retrieval is warranted. Many patients today opt for screening with cfDNA in lieu of invasive testing with CVS and amniocentesis. Standard cfDNA testing only screens for the most common chromosomal aneuploidies: trisomies 21, 18 and 13, and the sex chromosomes. Based on the reported cases of fetal lateral neck cysts, the standard cfDNA testing would likely detect these aneuploidies. However, the present study demonstrates that trisomy 9 may be included in the differential diagnosis when a fetal lateral neck cyst is detected, especially in the context of an increased nuchal translucency. If a patient declines diagnostic testing and opts for non-invasive fetal testing, we recommend a cfDNA that reports on all chromosomes.