First trimester three-dimensional ultrasonographic diagnosis of diastrophic dysplasia: a case report and review of the literature

Introduction

Diastrophic dysplasia is a rare disorder characterized by rhizomelic micromelia, cleft palate, micrognathia, dysmorphic ear lobes (cauliflower ears), kyphoscoliosis, limited joint mobility, congenital talipes equinovarus, and ‘hitchhiker’ thumbs [2]. We present a case of diastrophic dysplasia diagnosed by 2- and 3D ultrasound; the pregnancy was terminated at 13 weeks of gestation.

Case report

A 28-year-old woman, gravida 3 para 1 abortion 1, was referred to our Maternal Fetal Medicine Unit at 13 weeks’ gestation following the detection of increased nuchal translucency in the first-trimester scan. Her medical history was unremarkable. There was no history of consanguinity or previous genetic disorders in her family. Ultrasonography revealed a fetus consistent with 13+3 weeks (crown rump length: 74.09 mm) with increased nuchal translucency (5.81 mm). However, all extremities were seen to be markedly short (femur length: 6.49 mm, consistent with 12 weeks); therefore, a transvaginal ultrasonography examination was performed. On the transvaginal scan, ‘hitchhiker’ thumb (Figure 1A), relatively narrow thorax, varus deformity of the great toe (Figure 1B), and micrognathia (Figure 1C) were detected. ‘Hitchhiker’ thumbs and ‘Buddha’ position (Figure 2) were confirmed by 3D ultrasonography (Accuvix A30, Samsung Medison, Seoul, Korea). The combination of these findings was compatible with the diagnosis of diastrophic dysplasia. Chorionic villus sampling for fetal karyotyping was performed and reported as normal. After prenatal genetic counseling, the family elected to terminate the pregnancy by vaginal prostaglandin administration at 14 weeks. Autopsy findings confirmed the diagnosis of diastrophic dysplasia (Figures 3A and 3B); low-set ears were also present (Figure 3A).

Figure 1

Two-dimensional ultrasound examination of the fetus. (A) White arrow indicating the ‘hitchhiker’ thumb. (B) White arrow showing the varus deformity of the great toe. (C) White arrow indicating micrognathia.

Figure 2

Three-dimensional ultrasonographic view shows ‘hitchhiker’ thumb.

Figure 3

Necropsy pictures of the fetus.

(A) View of macroscopic features showing the ‘hitchhiker’ thumbs, short upper extremity, severe micrognathia, and low-set ear. (B) Short lower extremity with clubbed foot.

Discussion

Diastrophic dysplasia is a rare and non-lethal skeletal dysplasia. When diagnosed before viability, the option for pregnancy termination should be explained to the parents. Children with diastrophic dysplasia face enormous difficulties due to progressive contractures and deformities, the necessity of orthopedic intervention, and the risk for neurological complications because of cervical spine anomalies [10].

In the medical literature, there are seven case reports of prenatal diagnosis of diastrophic dysplasia, including eight prenatally diagnosed fetuses. Long bone shortening and hitchhiker thumbs were shown in all these cases. Details are given in Table 1 [1, 3, 4, 7–9, 11].

Additional abnormalities in this case were cleft palate, micrognathia, low-set ears, small nose, and hemangioma.

The diastrophic dystrophy sulfate transporter gene encodes a membrane sulfate transporter anion protein that is necessary for sulfation of the glycosaminoglycans that comprise the cartilage matrix. The gene is located on the long arm of chromosome 5q.31-q.34. The c.862 C>T (R279W) mutation is the most common mutation in Caucasians [6]. Honório et al. first revealed the prenatal molecular diagnosis of diastrophic dysplasia without previous history [3].

To our knowledge, there are three case reports in the medical literature about the first-trimester diagnosis of diastrophic dysplasia [1, 5, 8]. However, none of the case reports included 3D ultrasonographic examination. Sepulveda et al. reported only that 3D ultrasound had been proposed in a second-trimester fetus for confirming suspected diastrophic dysplasia [7]. We described ‘hitchhiker’ thumbs and ‘Buddha’ position of the lower extremity by 3D ultrasound in the first trimester. Our case report describes the first-trimester 3D ultrasound findings in a case of diastrophic dysplasia.

In these cases, if family history is absent, accurate early prenatal diagnosis is usually difficult. Some sonographic markers as mentioned above are present by the first trimester of gestation. Ngo et al. first described increased nuchal translucency in a fetus with diastrophic dysplasia [5], but this feature has not been reported in another case until now. We found increased nuchal translucency in this fetus. Thus, diastrophic dysplasia should be kept in mind in a fetus with increased nuchal translucency.

In conclusion, with the additional information obtained from 3D ultrasonography, prenatal diagnosis of diastrophic dysplasia is possible even in the first trimester. Evolving imaging techniques improve prenatal diagnosis of fetal anomalies. The 3D examination in first-trimester fetuses should be utilized more for a precise diagnosis of skeletal dysplasias.