Short bi-iliac distance in prenatal Ullrich-Turner syndrome

INTRODUCTION

The Ullrich-Turner syndrome (UTS) affects 1 in 2,500 to 5,000 newborn females [Gravholt et al., 1996; Lespinasse et al., 1998]. It is caused by the absence-totally or in part- of one X chromosome (45,X). At birth, UTS girls present a spectrum of anomalies varying from phenotypically normal girls to girls who exhibit all the typical features of UTS. The two main features are short stature and ovarian dysgenesis, but a variety of somatic features such as lymphedema of the hands and feet, webbed neck, low posterior hairline, multiple pigmented naevi, pterygium colli, cubitus valgus, widely spaced nipples, high arched palate, short metacarpals, and hyper convex fingernails (outer phenotype) are associated with UTS. More rarely, kidney anomalies and coarctation of aorta (inner phenotype) are present [De Paepe and Matton, 1985].

Recent investigations have focused on the association between the differences in genotype and the differences in phenotypic appearance in UTS [Amiel et al., 1996; Lespinasse et al., 1998; Skuse et al., 1999; Uematsu et al., 1999]. Other studies have presented anthropometric and body proportion measurements of UTS girls and women [Lyon et al., 1985; Hughes et al., 1986; Bernasconi et al., 1994; Sempé et al., 1996; Gravholt and Naeraa, 1997; Uematsu et al., 1999] or radiographic characteristics of the syndrome [Dalla Palma and Cavina, 1966]. Apart from distinguishing specific UTS features, these measurements also enable clinicians to evaluate the effects of sex and growth hormone treatment.

Only a few investigations have concentrated on skeletal development in UTS fetuses. In one investigation, the appearance of unilateral or bilateral cervical ribs has been described [Kjær and Fischer Hansen, 1997]. Also, the body proportions are different compared to proportions in normal fetal development [FitzSimmons et al., 1994; Andersen et al., 2000]. The purpose of the present study was to evaluate the bi-iliac distance and the caudo-cranial position of the iliac bones in UTS fetuses compared to recently published standards for normal fetuses [Hartling et al., 2001].

MATERIALS AND METHODS

Whole-body radiographs in antero-posterior projections of 24 UTS fetuses with crown-rump lengths (CRL) 106–220 mm were included in the study. The fetuses derived from spontaneous or therapeutic abortions and were examined according to the required autopsy procedure at the hospital where they were delivered. The fetuses were radiographed as part of the autopsy procedure. All but three fetuses were karyotyped. In these latter three fetuses, the Ullrich-Turner syndrome diagnosis was based on the phenotypic appearance. The fetuses derived from Hvidovre University Hospital, Copenhagen, and the Royal Hospital for Sick Children, Edinburgh. Example of the appearance of a whole-body radiograph is seen in Figure 1.

From each radiograph, two horizontal and two vertical (caudo-cranial) distances were measured to estimate the position of the iliac bones. The measuring was performed with a Helios digital slide caliper. The method has recently been described [Hartling et al., 2001].

Bi-Iliac Distance

Two horizontal distances, named the outer and the inner bi-iliac distance, were measured. The two bi-iliac distances are illustrated in Figure 2. A line combining the upper contours of the iliac bones, here called the upper iliac line, was placed on each radiograph.

Outer bi-iliac distance

Perpendicular to the upper iliac line, two lines, called the outer iliac lines, were constructed tangent to each of the most lateral parts of the iliac bones. The outer bi-iliac distance was measured as the distance between the outer iliac lines.

Inner bi-iliac distance

Perpendicular to the upper iliac line, two lines were constructed tangent to the most medial parts of each of the iliac bones. These lines were named the inner iliac lines. The inner bi-iliac distance was the distance between the two inner iliac lines.

RESULTS

The values from the UTS fetuses were compared with values from normal fetuses.

Bi-Iliac Distances

The outer and inner bi-iliac distances both increased almost linearly compared to CRL.

Outer bi-iliac distance in UTS fetuses compared with normal fetuses

The outer bi-iliac distance in UTS fetuses was consistently shorter than in normal fetuses, on average 2.58 mm. This is illustrated in Figure 3. However, we found no difference in growth rate between UTS and normal fetuses (P = 0.10).

Inner bi-iliac distance in UTS fetuses compared with normal fetuses

The inner bi-iliac distance in UTS fetuses was shorter than in normal fetuses, but the difference related to the size of the fetus was not constant. We found a significantly lower growth rate, in fact only half the growth rate, among UTS fetuses compared with normal fetuses. The difference in growth rate was estimated at −0.035 mm/mm (0.008; P < 0.0001). The relationship is shown in Figure 4.

Caudo-Cranial Position of Iliac Bones

Upper caudo-cranial position

The position of the iliac bones was lower in UTS fetuses compared to the position in normal fetuses [0.661 mm (0.285); P = 0.024]. This difference is illustrated in Figure 5.

Lower caudo-cranial position

We found no significant difference between UTS and normal fetuses, either in the position of the iliac bones (P > 0.10) or in growth rate. The relationship to CRL is common for the two groups, which is illustrated in Figure 6.

DISCUSSION

The present investigation revealed that both the outer and inner bi-iliac distances were significantly shorter in UTS fetuses compared with normal fetuses. This might have been expected because UTS girls and women have been found to be smaller than normal individuals in other body proportions [Rongen-Westerlaken et al., 1993; FitzSimmons et al., 1994]. We also found that for the inner bi-iliac distance, the growth rate compared to CRL in UTS fetuses was significantly lower than in normal fetuses. This finding is interesting because it suggests not only a lesser growth but also a different growth pattern in UTS fetuses compared to normal fetuses.

Regarding the caudo-cranial position of the iliac bones in proportion to the lower vertebral column, there was no significant difference for the lower caudo-cranial position, but the upper caudo-cranial position was significantly lower in UTS fetuses than in normal fetuses, when compared to the first sacral vertebral body. This result is difficult to interpret, as it could be caused by a slower growth of the vertebral column.

The bi-iliac distance has not previously been described in Ullrich-Turner fetuses, but in a study by Gravholt and Naeraa [1997], the (outer) bi-iliac distance (together with other body proportions) was measured on adult women with UTS. Interestingly, the bi-iliac distance in these women was found to be 1.4 standard deviation scores (SDS) above average. This finding apparently contradicts the results of the present study. An explanation could be that body proportions in UTS differ with age in a different way than in normal individuals. This was found to be the case for sitting height and leg length in individuals with UTS in a study by Rongen-Westerlaken et al. [1993]. However, the most probable explanation of the apparent discrepancy is that the methods of measuring in the two studies differ considerably. In the study by Gravholt and Naeraa [1997], the measurement of the bi-iliac distance was performed with a tape ruler on living individuals with UTS and therefore includes some of the abdominal circumference. In the present study, the bi-iliac distances were measured on radiographs and therefore represent the shortest distance between the iliac bones.

In the present study, measurements was performed on 24 radiographs of UTS fetuses. The results from this rather limited number of fetuses need to be confirmed in an extended study. Three of the UTS fetuses had not been karyotyped, but were diagnosed as having UTS on the basis of the pathology (large neck hygroma, edema, additional cervical ribs). These three fetuses have been included because the pathologist considered the diagnosis of UTS to be very likely. Another inconsistency between the UTS fetuses in the study was that some of the fetuses were mosaics (45,X/46,XX). These facts may have influenced the results, as only karyotyping can guarantee the genotype and as mosaics may have different phenotypes compared with both pure 45,X fetuses and normal fetuses. The use of CRL as an indicator of age might also be somewhat problematic in studies of UTS, as these fetuses are known to be small for their age. Thus, a UTS fetus is older than a normal fetus having the same CRL value. The difference in bi-iliac distance between UTS fetuses and normal fetuses with the same gestational age is probably even greater than what was found in this study, where CRL was used as a reference parameter for age.

In the past, only few investigations of the skeletal development in UTS have been performed. No study exists with which the results of this study can be directly compared. In a study by Kjær and Fischer Hansen [1997], UTS fetuses were found to have unilateral or bilateral cervical ribs. In another study by FitzSimmons et al. [1994], diminished growth of the long bones (femur, tibia, fibula, humerus, radius, and ulna) was detected by midtrimester in fetuses with UTS. Also, the cranial base complex and hand in UTS fetuses have been measured [Andersen et al., 2000]. It was found that the cranial base complex in second trimester UTS fetuses differed from that of normal second trimester fetuses and that UTS fetuses also had smaller hands and smaller hand bones. Apart from the investigations mentioned above, nothing was found in the literature about the skeletal system in UTS in prenatal life.

Prenatal studies of UTS are interesting and important for clarifying the onset of the deviant development in UTS, which is registered postnatally. Moreover, such information is valuable for clinical purposes. The prenatal assessment of abnormal skeletal development by ultrasonography can contribute in distinguishing between UTS and other anomalies but also in distinguishing between viable (or near-normal) UTS fetuses and UTS fetuses that have a phenotype which is not compatible with life [Koeberl et al., 1995; Amiel et al., 1996]. With increasing knowledge of phenotypic differences in UTS, genetic counseling can be improved.

Perinatal diagnosis of UTS is difficult. This is seen from the fact that only 20% of UTS girls are diagnosed at birth. The rest are diagnosed during childhood, or even later at puberty [Lespinasse et al., 1998]. Although chromosomal assessment of UTS is the standard for diagnosis, it is important to have as many phenotypic diagnostic criteria as possible for this syndrome because access to chromosome analysis is not always possible.