Thanatophoric dysplasia, type I

Case presentation

A 20-year-old woman (gravid 4, para 2-0-1) in the 18th week of pregnancy attended a baby shower where there was a sonographic baby picture boutique. The images seen at that sonogram suggested that the female fetus had short-limb dwarfism. The mother was referred to the obstetrical sonography group for further evaluation. Sonography performed at approximately 23 weeks gestation again demonstrated marked short-limb dwarfism, and it was believed that this was a lethal chondrodysplasia. However, the mother wanted to confirm this diagnosis before delivery. Therefore, a low-dose computed tomography (CT) scan of the fetus and maternal pelvis was performed on a Siemens Somatom Definition AS (Munich, Germany) at settings of 100 kV and 36 mA (Figures 1, 2 and 3), at 26 weeks gestation. Subsequently, at 28 weeks with the pregnancy complicated by progressive polyhydramnios, the mother developed premature labor. Labor was allowed to progress and a stillborn infant was delivered. Post delivery skeletal survey (Figure 4) was obtained.

Figure 1
figure1

Transaxial computed tomography (CT) image of the maternal pelvis acquired with low-dose acquisition. The fetal skeletal within the pelvis of the obese patient is not well seen.

Figure 2
figure2

Sagittal 3-D fetal reconstruction from the axial views. Straight white arrows indicate the markedly flattened or platyspondylic lumbar vertebral bodies. Open arrows points to the curved, shortened femoral bilaterally. 3-D reconstructions allow better definition of the skeleton than axial images.

Figure 3
figure3

Coronal reconstructed fetal skeleton. The relatively normal skull configuration is seen without a clover-leaf shape. Short limbs (open arrows), short thin ribs and thin clavicles (straight arrows) are seen.

Figure 4
figure4

(a) Frontal and (b) Lateral post mortem radiographs of the stillborn infant. The frontal radiograph demonstrates the lumbar inverted ‘u’ appearance of the vertebral body and posterior elements. The lateral radiograph demonstrates the marked platyspondyly slightly more significant in the mid portion of the vertebral body (straight arrows). Curved arrow on the lateral radiograph demonstrates the frontal bossing, accentuated by mid-face hypoplasia.

Denouement and discussion

The use of low-dose CT scan to confirm the diagnosis of lethal chondrodysplasia has been recently described.1 This procedure allows better definition of the skeleton than both sonography and maternal pelvic magnetic resonance imaging. The American College of Radiology's reference dose for radiation is CT dose index volume (CTDIvol). In our very obese patient, the CTDIvol was 13.9 mGy. The CT dose index volume is roughly equal to the fetal dose in this patient.2, 3 The American College of Radiology's CT accreditation reference CTDIvol in abdominal CT is 25 mGy, which corresponds to an embryo dose of 35 mGy in a 70-kg patient. Thus, our fetal dose was within acceptable limits. This value is below the reported dose threshold for the induction of teratogenesis.4

The fetal CT and the post natal images both demonstrate thanatophoric dysplasia (TD), type 1, an autosomal dominant condition, uniformly lethal in the perinatal period. TD is the most common of the platyspondylic lethal skeletal dysplasias (PLSDs). It is divided into type 1 with a normal skull confirmation, as in this case, and type 2 with a clover-leaf skull (kleeblatschadel).5 Both TD1 and TD2 are due to mutations in the fibroblast growth factor receptor 3 gene (FGFR3). There is a single known mutation accounting for cases of TD2 and approximately 12 missense mutations accounting for cases of TD1.6 There are two additional types of PLSD, the Sandiego type and the Torrance–Luton type. The Sandiego PLSD is a slightly milder disease than TD but is associated with mutations in the FGFR3 gene. Torrance–Luton is a milder disease, sometimes associated with long-term survival, and due to a mutation in the type II collage gene (COL2A1).7, 8

The characteristic radiographic findings of all forms of PLSD are marked platyspondyly. In TD, the vertebral bodies and posterior elements in the lumbar region, viewed on frontal radiographs, have a ‘n’ or inverted ‘u’ appearance. Characteristically the midportion of the vertebral body may be slightly flatter than the anterior and posterior portions, unlike Sandiego and Torrance–Luton type, which are more wafer-like throughout and do not have an inverted ‘u’ appearance usually. The skull is essentially normal in appearance in TD1, except for frontal bossing, but has a clover-leaf configuration in TD2. In both types, there is usually mid- and upper-face hypoplasia. In TD, the clavicles and ribs are thin, and the scapula slightly hypoplastic. The sacrosciatic notches are narrowed, and the acetabular roofs are flat. Secondary ossification centers may develop in the ischia and ilia in both TD and Sandiego type PLSD.6 Markedly shortened limbs are present, which in TD1 have a characteristic bowed appearance resembling a telephone receiver, with a medial metaphyseal spur.5 In TD2 and Sandiego and Torrance–Luton PLSD the femurs are straighter. The fibula in TD is usually markedly shorter than the tibia. The findings in this patient were characteristic of TD1, with a grossly normal well-ossified skull, with mid-face hypoplasia and frontal bossing, marked platyspondyly with lumbar inverted ‘u’ pattern, deformity of the femurs with a telephone receiver configuration and markedly shortened fibulae (Figures 3 and 4).

Polyhydramnios usually develops in the second and third trimesters. Death usually occurs within hours or days after delivery from respiratory insufficiency. Rare long-term survivors, even to adulthood, have been described, especially among patients with Torrance–Luton-type PLSD.7

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Correspondence to T E Herman.

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Herman, T., Siegel, M. Thanatophoric dysplasia, type I. J Perinatol 32, 476–478 (2012). https://doi.org/10.1038/jp.2011.108

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