Prenatal diagnosis of isolated agnathia with two and three-dimensional ultrasound

Introduction

We report a very rare case of isolated agnathia diagnosed at 21 weeks’ gestation and state the importance of three-dimensional (3D) ultrasound in demonstrating facial details.

Case report

A 33-year-old woman, gravida 2, para 1, was referred to the Ultrasound Unit of the Hospital Clinico Universitario, Valencia, Spain, for a routine ultrasound scan.

At 13+2 weeks’ gestation, the nuchal translucency measured 1.37 mm. We carefully observed the profile of the fetus and there was no suspicion of agnathia (see Figure 1). Unfortunately, we did not perform the retronasal triangle view that could have detected the defects of the mandible at this stage [5].

Figure 1

Sonographic measurement of nuchal translucency during the first trimester. At this stage the diagnosis of agnathia was not taken into account.

A morphological scan was performed at 21+4 weeks’ gestation, showing a male fetus, fetal biometry consistent with gestational age, and normal amniotic fluid volume. Examination of the fetal anatomy revealed severe anomalies of the mandible, cleft lip and palate, and low implantation ears. There were no midline alterations. A survey of the rest of the anatomy was then conducted, without any pathological findings.

Midsagittal sections of the face were obtained showing evidence of alterations in fetal profile, suggesting the absence of the mandible. A transverse section of the skull substantiated the diagnosis (see Figure 2). Findings were supplemented with 3D ultrasound (see Figure 3A,B), a technique especially important at this stage of agnathia to demonstrate facial appearance and low implantation ears. The use of 3D ultrasound is clearly helpful in identifying the nature and extent of the anomaly, and is also important for parental counseling [1].

Figure 2

Two-dimensional ultrasound revealing the craniofacial defect: midsagittal views of the fetal profile in which mandible is not visible (A, B), coronal view of the cleft lip (C) and axial view showing the cleft and the absence of mandible (D).

Figure 3

Prenatal ultrasound assesment of agnathia: three-dimensional reconstruction of the face showing cleft lip (A) and the large defect of the mandible (B). Fetal necropsy showing mandible agenesia, right cleft lip and palate, low-set ears and left preauricular node (C, D).

Amniocentesis with karyotype and chromosomal microarray were normal. The parents were counseled by our team and opted for termination of the pregnancy. The fetal necropsy confirmed these findings. Macroscopic examination was consistent with mandible agenesis, right cleft lip and palate, low-set ears, and left preauricular node (See Figures 3C,B). The right choana was not permeable. The tongue was partially attached to the lateral walls of the mouth. Microscopic examination did not reveal new findings.

Discusion

Agnathia is an extremely rare malformation that most frequently occurs with other associated malformations, such as holoprosencephaly, hydranencephaly, and Dandy-Walker malformation. Isolated agnathia is a much more infrequent entity [7].

It is characterized by an absent mandible and anomalies of the tongue, generally aglossia or hypoglossia, and ears (low implantation, otocephaly, or medially fused ears). The diagnosis in its isolated form is much more difficult, and most cases are diagnosed during the third trimester or at birth. Even if an appropriate profile of the fetal face is performed the diagnosis may be missed. The diagnosis can be made by 3D ultrasound and improves the genetic counseling.

The absence of the mandible may cause respiratory distress after birth resulting in perinatal death, therefore, parents may decide to terminate the pregnancy as a result of the poor prognosis [2].

The etiology of agnathia is still unknown. Most probably, an incident occurring between the fourth and seventh week of gestation can induce abnormal neural crest cell migration, resulting in alterations of the structures derived from the first branchial arch. Some studies suggest that these derivatives and oral-facial development are vulnerable to cytomegalovirus infection. When the infection occurs early in pregnancy, the sequelae might differ from those related to infection acquired later [6].

Even though there is one case reported at 12 weeks’ gestation, there are not many cases of isolated agnathia previously reported, and even fewer with 3D ultrasound [3]. This condition could be detected at first trimester through nuchal translucency carried out as recommended by The Fetal Medicine Foundation, for which getting a midsagittal view of the fetal profile is mandatory. The retronasal triangle view can be a valuable technique for detecting this condition, showing the absence of the mandibular gap or not identifying the mandible. In addition, first trimester screening could be an opportunity for early sonographic assessment of pathologies in general and those of facial clefts in particular; due to the smaller size of the fetus, it could be easier to scan the orofacial region [4].

This case shows that taking sagittal views of the fetal profile and chin may detect anomalies of this nature, and should be part of the routine mid-trimester fetal ultrasound scan.