Fetal hemivertebra: a rare form of 18q deletion prenatal presentation

Abstract

The 18q deletion is a rare condition with several described features. A common phenotype includes short stature, microcephaly, facial defects, small feet, intellectual disability and hypotonia.

We present a rare case of a fetus with del18q22.1q23 whose diagnosis was obtained by amniocentesis after a routine ultrasound at 20 weeks, where a hemivertebra was detected.

Congenital hemivertebra is infrequent and is rarely associated with chromosomal anomalies. Expectant management can be advocated in isolated hemivertebra. This report shows that a hemivertebra can be an isolated prenatal finding in del18 so it is important to screen for, and exclude, chromosomal anomalies.

Background

First described by de Grouchy et al in 1964, deletion of the long arm of chromosome 18 has been reported over 100 times.¹ The estimated incidence for all types of 18q deletions is 1:55 000 births.² The most common cause are de novo mutations, but a dominant transmission of a partial 18q deletion from the mother has been previously reported.³

Current literature suggests that a wide phenotypical spectrum exists among patients with 18q deletions. The phenotype differences may be related to the size or cut point of the deletion.⁴ In 1999, Cody et al described 42 individuals with 18q deletions. The most common features were short stature, microcephaly, palatal defects, short frenulum, carp-like mouth, short palpebral fissures and external ear anomalies. Regarding skeletal anomalies, disproportionately small feet and short lower limbs were the most common features. Nonetheless, scoliosis was also identified in three patients.⁵ This deletion is, likewise, associated with mental retardation (mild to severe) and hypotonia.⁴

The authors present a rare case of del18q22.1q23 diagnosed in prenatal period, due to the finding of hemivertebra on 20 weeks’ prenatal ultrasound.

Case presentation

A healthy primigravida in her 20s had an uneventful pregnancy until 20 weeks’ gestation. There was no family or personal history of genetic diseases. Ultrasound examination found a single thoracic hemivertebra, scoliosis and a single umbilical artery (figures 1 and 2). No other abnormalities were reported. Fetal echocardiography was also normal. The patient underwent amniocentesis at 22 weeks of gestation. Fetal genetic analysis revealed an abnormal array-comparative genomic hybridisation ‘arr 18q22.1q23 (61838447_77982126)x1’, which is responsible for the occurrence of 18q (OMIM * 601808) deletion syndrome.

Figure 1.

Two-dimensional ultrasound: hemivertebra image (arrow).

Figure 2.

Three-dimensional ultrasound: hemivertebra image (arrow).

Outcome and follow-up

The couple was informed of the findings and chose to terminate the pregnancy. A 559 g stillborn girl was delivered at 23 weeks’ gestation with obvious deformation of the spine (figure 3) and the ultrasound findings were confirmed with a simple X-ray (figure 4). Autopsy showed mild retrognathia, dysplastic external ear, D9 hemivertebra, with deviation and partial collapse of D8 and D10 vertebrae, ostium primum-type atrial septal defect and brain white matter abnormalities. There were no significant upper or lower limb anomalies.

Figure 3.

Stillborn with notorious deformation of the spine (arrow).

Figure 4.

Hemivertebra (arrow) confirmed in a simple X-ray.

The couple’s karyotypes were normal.

Discussion

Dowton et al reported a case of a newborn diagnosed with 18q deletion with multiple ribs and malsegmentation anomalies of the thoracic vertebrae, including hemivertebrae and butterfly vertebrae. Dowton et al’s case also had a single kidney and myelomeningocele.⁶ To the authors’ knowledge, the case we present is the first case of hemivertebrae associated with 18q deletion with prenatal diagnosis.

A hemivertebra is a congenital deformation of the spine where only half of the vertebral body develops. The defect can affect a single or multiple vertebrae. The vertebrae typically develop during the sixth week of gestation and the incidence of hemivertebra is estimated at 0.5–1 per 1000 births.⁷

The diagnosis of fetal hemivertebrae on prenatal ultrasound requires meticulous examination and is usually possible by demonstrating the spine in the coronal and sagittal planes. The deformity manifests as a triangular body structure, usually smaller than a vertebra, which acts as a wedge against the normal vertebral body. Three-dimensional ultrasound can provide additional information regarding the fetal spine anatomy.

The prognosis and recurrence of fetal hemivertebra are related to the type, location and the number of affected vertebrae, and the presence of associated abnormalities. Isolated fetal hemivertebra has been found to have a favourable prognosis.⁸ Although chromosomal abnormalities are not commonly associated with hemivertebrae, they may have syndromic associations, such as Jarcho-Levin syndrome, Klippel-Feil syndrome, and VATER or VACTERL associations.⁶

In an isolated vertebra, there was no increased risk of recurrence in other pregnancies, but if multiple vertebrae are affected, the risk increases to 5%–10%.⁸

Obstetric counselling and management for fetal hemivertebrae depend on the time of diagnosis, the number of vertebral abnormalities, and the presence of associated malformations or genetic alterations. If only one vertebra is affected and no other fetal malformations or chromosomal abnormality is detected, conservative management of the pregnancy can be offered. The option of pregnancy termination should be offered when involvement of multiple vertebrae or additional organ systems is present.

Taking into consideration the high variability of clinical features in patients with 18q deletion syndrome, we believe that molecular karyotyping is essential. The array is key to establish the diagnosis, determine the incidence and connect unknown features of the syndrome.

To the best of our knowledge, this is the first report of prenatal diagnosis of hemivertebrae associated with del18q22.1q23, which highlights the importance of investigating genetic abnormalities in the presence of prenatal congenital vertebral abnormalities.

Learning points.

• Congenital hemivertebra is rare, and prenatal ultrasound requires a careful examination of the fetal spine.

• Hemivertebra could be the unique finding of chromosomal anomalies.

• The 18q deletion is frequently associated with microcephaly, facial alteration and intellectual disability, but uncommon findings, such as hemivertebra, may be the sole ultrasound presentation.

Ethics statements

Patient consent for publication

Parental/guardian consent obtained.