HDlive Studio and HDlive Silhouette Mode for Antenatal Diagnosis of Apert Syndrome

INTRODUCTION

Apert syndrome is a rare autosomal dominant disorder with an estimated incidence of 1 per 65,000 live births.¹ It is characterized by craniosynostosis, which restricts the growth of the skull resulting in craniofacial abnormalities. Midfacial hypoplasia, symmetric cutaneous, and bony syndactyly of the limbs are the other characteristics of this syndrome.² Diagnosis is usually suggested by prenatal sonography^3,4 and confirmed by prenatal fibroblast growth factor receptor type 2 (FGFR2) mutation analysis.⁵ Numerous reports discussed the antenatal diagnosis of Apert syndrome using two-dimensional (2D) and three-dimensional (3D) ultrasound as well as magnetic resonance imaging (MRI).^3,4,6–13 However, to the best of our knowledge, this is the first report assessing the use of HDlive silhouette mode and HDlive Studio in antenatal diagnosis of Apert syndrome.

CASE REPORT

A 31-year-old pregnant nulliparous Japanese woman was referred to our hospital due to suspected skull bone abnormalities at 20 weeks and 1 day of gestation. 2D sonography showed a trilobate shape of the skull (Fig. 1A). HDlive Studio (Voluson E10, GE Healthcare Japan, Tokyo, Japan) clearly showed brachycephaly (Fig. 1B). The 3D maximum mode showed broad metopic and sagittal sutures, and large anterior and posterior fontanels (Fig. 2).

At 23 weeks and 1 day of gestation, HDlive silhouette mode confirmed the widened fontanels and sutures, and early closure of bilateral coronal sutures (Fig. 3). Conventional 3D images of the fetal limbs showed abnormalities of the fingers and toes at 27 weeks and 1 day of gestation (Fig. 4). HDlive Studio and HDlive silhouette mode clearly demonstrated the limb abnormalities in the form of fusion of the digits of fingers and toes at 28 weeks and 1 day (Fig. 5). Diagnosis of Apert syndrome was highly suggested.

At 41 weeks and 4 days of gestation, she was delivered vaginally of a viable female infant weighing 3,836 g, and the height was 52.5 cm. Apgar score was 7 (1 minute) and 9 (5 minutes), and the umbilical artery blood pH was 7.208. Postnatal examination confirmed brachycephaly and syndactyly of fingers and toes (Fig. 6). 3D CT showed the widened metopic suture and fontanels, and bilateral coronal sutures were closed (Fig. 7). Genetic study confirmed the presence of FGFR2 mutation (Fig. 8). Final diagnosis was Apert syndrome.

DISCUSSION

The cloverleaf-like appearance of the skull resulting from craniosynostosis in addition to the syndactyly is usually suggestive of diagnosis in cases of Apert syndrome.³ However, the appearance of the these differential features can be as early as 16 weeks of gestation,¹⁰ or delayed up to 32 weeks of gestation.¹⁴ Moreover, the craniosynostosis was not present in some cases.¹⁵ On the contrary, craniosynostosis is shared by other anomalies such as thanatophoric dysplasia, severe Crouzon syndrome, and Carpenter syndrome.¹⁶ Syndactyly can be easily identified especially the complex type involving bony fusion.¹⁷ However, the use of the 3D ultrasound in identifying the soft type of syndactyly becomes mandatory because it cannot be detected by conventional 2D sonography.¹⁶ Therefore, meticulous sonographic examination might be needed to detect these anomalies.

The use of 3D ultrasound has been previously described in cases of Apert syndrome.^8,12,18–20 In these studies, 3D ultrasound with the transparent maximum mode was found to be beneficial in demonstrating the closure of the coronal suture and widening of the metopic suture more clearly compared with conventional 2D sonography.^8,12,18,19 HDlive silhouette mode is one of the novel technologies to evaluate fetal bony structures.^21,22 In the current case, the HDlive silhouette mode clearly depicted the early closure of the coronal suture. To the best of our knowledge, this is the first study to evaluate fetal cranial sutures using the HDlive silhouette mode. Moreover, the HDlive silhouette mode enabled more clear recognition of the precise fusions of fingers and toes in comparison to conventional 3D ultrasound features. Limb anomalies are usually hard to be detected because of inappropriate limb positions or fetal movements, which make their identification difficult when only conventional 3D ultrasound is used.

In conclusion, HDlive Studio and HDlive silhouette mode may be a beneficial adjunct diagnostic tool beside the conventional 2D and 3D ultrasound for the precise diagnosis of Apert syndrome. Further studies are needed to confirm the true benefits of these technologies in the diagnosis of fetal craniosynostosis syndromes.

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