Prenatal diagnosis of a severe form of frontonasal dysplasia with severe limb anomalies, hydrocephaly, a hypoplastic corpus callosum, and a ventricular septal defect using 3D ultrasound: a case report and literature review

Abstract

Background: Frontonasal dysplasia (FND) is a rare congenital anomaly resulting from the underdevelopment of the frontonasal process, and it can be syndromic or nonsyndromic. The typical features of FND include a deformed nose and ocular hypertelorism, which are sometimes associated with cleft lip and/or palate. Only approximately 10 cases of prenatally diagnosed nonsyndromic FND have been reported in the past 30 years.

Case presentation: A 33-year-old woman (G2P1) was referred to our center at 20 gestational weeks for bilateral hydrocephaly. We detected typical features of FND, including severe hypertelorism, median nasal bifidity, a minor cleft lip, and multiple limb anomalies using three-dimensional (3D) ultrasound. A hypoplastic corpus callosum, unilateral microtia, and a ventricular septal defect were also detected. Genetic testing, including karyotype analysis, copy number variation (CNV) analysis, trio-whole exome sequencing (trio-WES), and trio-whole-gene sequencing (trio-WGS), was performed; however, we did not find any de novo gene variants in the fetus as compared to the parents. Postmortem examination confirmed the prenatal diagnosis of FND.

Conclusion: The present case expands the wide phenotypic spectrum of prenatal FND patients. 3D ultrasound is a useful tool for detecting facial and limb deformities.

Keywords: 3D ultrasound; Frontonasal dysplasia; Genetics; Prenatal diagnosis.

Fig. 1

(a) 3D surface rendering showing facial dysmorphism, including a broad nasal root without a nasal tip and divided nostrils resembling two eyes. (b) 3D ultrasound showing an abnormal profile and a deformed right hand. (c) The coronal plane of the face showing a minor median upper lip cleft measuring 1.5 mm. (d) The axial plane of the eyes showing ocular hypertelorism, with an interorbital diameter of 16.6 mm and orbital diameters of 9.8 mm and 9.7 mm. (e) The abnormally shaped pericallosal artery with high-quality slow flow in the midsagittal plane of the brain demonstrating hypoplasia of the corpus callosum. (f) The coronal plane of the brain showing bilateral hydrocephalus with round anterior horns. (g) Note a perimembranous ventricular septal defect measuring 2.5 mm. (h) 3D ultrasound showing that the left club foot, and the left lower limb were shorter than the right limb

Fig. 2

(a-d) The normal whole genome maps of the fetus, the father, the mother, and the brother

Fig. 3

(a) A picture of the fetus after induced delivery showing multiple malformations of the face and limbs. (b) A picture of the right hand showing syndactyly of four fingers. (c) A picture of the lower limbs showing that the left lower limb was hypoplastic with a club foot and syndactyly; note that the left leg was shorter than the right leg. (d) The right profile showing a normal right ear. (e) The left profile showing left low-set microtia