Upper limb hemimelia in a twin pregnancy which was obtained by an ICSI and PGD in a woman with mosaic Turner's syndrome and the prognosis

ABSTRACT

Turner's syndrome (TS) is depicted as a total or partial absence of X chromosome, and occurs in approximately 1/2200 of live born females. Generally, mosaic patients are diagnosed following karyotype analysis due to recurrent pregnancy loss, repeated in vitro fertilization (IVF) failure, and a history of malformed babies. The purpose of this case report is to show that even a selection of normal karyotype embryos can result in abnormalities for those with mosaic TS. A 32-year old patient who underwent IVF after ICSI-PGD, and was diagnosed with 45X/46XX karyotype. At the 12-week scan, one of the fetuses had an upper limb hemimelia in one arm, and feticide was applied to that fetus. The patient delivered a healthy, 2980 g female baby at the thirty-eighth week. In mosaic TS pregnancies (even those obtained by ICSI-PGD), fetal anomaly risk is high. Therefore, careful prenatal scanning is needed for these pregnancies.

KEYWORDS:

• Fetal anomaly
• Hemimelia
• ICSI
• mosaic Turner's syndrome
• PGD

INTRODUCTION

Turner's syndrome (TS) is depicted as a total or partial absence of one X chromosome, and occurs in approximately 1/2200 of live born females.¹ Nearly 43–49% of patients that represent cases with classical TS are monosomic for an X chromosome (45, X). The remaining patients are mosaic cases carrying normal and abnormal cell lines together (most of them had45, X/46, XX karyotypes) (15–23%). Mosaic TS patients are more likely to experience normal pubertal development, regular menstrual cycles, and to conceive spontaneously compared to those with 45, X monosomy.^2-5 Generally, mosaic patients are diagnosed following karyotype analysis due to recurrent pregnancy loss, repeated in vitro fertilization (IVF) failure, and history of malformed babies.^6-8 In the past few years, authors have recommended intracytoplasmic sperm injection and preimplantation genetic diagnosis (ICSI-PGD) for infertility treatment of the patients with mosaic Turner Syndrome.⁹ The purpose of this case report was to show that even a selection of normal karyotype embryos can result in abnormalities for those with mosaic TS. Careful scanning should be offered to all mosaic TS pregnancies.

CASE PRESENTATION

This case report was approved by the local ethics committee in accordance with the Declaration of Helsinki. Informed consent was obtained from participant.

A thirty-two year old patient with gravida 2, para 0, and abortion 1 was counseled for chromosome abnormalities, and 45X(4)/46XX(36) karyotype was diagnosed. The mosaic cell line ratio detected 11%. By using fluorescence in situ hybridization probes, preimplantation cytogenetic analysis (ICSI-PGD) of the embryos was obtained from the patient with mosaic TS. The analysis was performed three times. During the first trial, 1/11 embryos were normally karyotyped, and that one was transferred. During the second trial, 1/12 embryos were healthy and were transferred, but pregnancy was not obtained. On the third trial, 4/12 embryos were healthy and two of them tranferred, while two of them were frozen. After an unsuccessful third trial, the two frozen embryos were transferred. With this last trial, a dichorionic diamniotic twin pregnancy was obtained and antenatal examinations were started.

At the first trimester scan, one of the fetuses had an upper limb hemimelia (ulnar and radial) in one arm (Figs. 1,2), and feticide was applied to that fetus. At the sixteenth week, the remaining fetus had a choroid plexus cyst, but it was disappeared at the twenty-second week. The patient delivered a healthy, 2980 g female baby at thirty-eight weeks.

FIGURE 1. 12-week scan one of the fetuses, who has an upper limb hemimelia.

FIGURE 2. 13 weeks 4 days fetus with upper limb hemimelia.

DISCUSSION

Some studies have shown that TS women who are able to conceive are at increased risk for miscarriage, stillbirths, and malformed babies.^10–11 Tarani et al. analyzed 160 spontaneous pregnancies in 74 women with TS, and reported that 67.3% of the pregnancies with a 45,X/46,XX karyotype and 70.8% of the pregnancies with a 45,X/46,XX/ 47,XXX karyotype resulted in miscarriages or malformed fetuses.⁶

In our case, after one abortion, ICSI-PGD therapy was applied three times, but pregnancy was not obtained. During the fourth trial, a dichorionic diamniotic pregnancy occurred, but one of the fetuses had an upper limb hemimelia, and feticide was performed to that fetus. There was no amniotic band. Family history was questioned, but this anomaly had not been seen before.

There are at least four ways in which limb deficiencies can be caused: intrauterine amputation from amniotic bands, disruption of the developing arterial supply, environmental factors, and errors in the genetic control of limb development (12). The oldest and most commonly held etiology for congenital amputation in the past was amniotic bands. There is evidence that amniotic bands can form a constriction around the developing limb that interferes with the growth of the limb, resulting in any degree of damage, from a minor constriction band around a limb that is otherwise normal, to a complete transverse amputation. The disruption of the developing arterial supply may cause a severe ischemic aggression to the limb bud, thus producing the anomaly with varying degrees of severity and associated lesions. Environmental causes have been identified in approximately 10% of malformations: maternal infections or disease, uterine constraint, and exposure of the embryo to recognized drugs, chemicals, irradiation, or hyperthermia. Modern genetics have shown that the development of the limb is a complex phenomenon that requires the precise interaction of a large number of genes and their effects.¹² Uterine hypoplasia and related reduced uterine perfusion is secondary to significant changes in the utero-ovarian vascular anatomy, and subclinical uterine abnormalities in TS cases have been implicated in the etiology of miscarriages.^13-14

The same factors may play a role in the etiology of limb deficiency. In this case, pregnancy continued up to the thirty-eighth week. Gestational diabetes and preeclampsia can also exist frequently in TS pregnancies, but in our case, these problems were not seen.

Cerebral paresis, neuropsychological disorders, aortic coarctations, cleft lips, and palate and congenital tumors were detected in 5 (7%) of 68 children born to women with TS.¹⁵ Table 1 shows most frequent fetal abnormalities associated to women with TS (4,15).

TABLE 1. Most frequent fetal abnormalities associated to women with TS (4,15)

Fetal Birth Defect Or A Serious Illness	%
Cerebral Paresis	1.4
Neuropsychological Disorder	1.4
Coarctation Of The Aorta	1.4
Cleft Lip And Palate	1.4
Congenital Tumor	1.4
Congenital Hydrocephalus	1.6
Ambiguous Genitalia	1.6

Our case is the first report regarding hemimelia diagnosed in a pregnancy that was obtained by ICSI-PGD in a patient with mosaic TS. In conclusion, in mosaic TS pregnancies (even those obtained by ICSI-PGD), fetal anomaly risk is high. Therefore, a careful scan is needed for these pregnancies.

DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST

No potential conflicts of interest were disclosed.