Table of Contents

HK J Paediatr (New Series)
Vol 23. No. 4, 2018

HK J Paediatr (New Series) 2018;23:298-301

Case Report

Long-term Extrauterine Survival in a Triploid Infant: A Review of the Clinical Features of Live-born Infants with Triploidy

S Hashimoto, L Igarashi, M Kobayashi, H Tsutsumi


Abstract

Almost all triploid fetuses abort spontaneously in the first trimester; live-born triploid infants are rare. We herein report a triploid infant who survived for >250 days. The infant was delivered at 33 weeks 4 days of gestation because of severe fetal growth restriction. The birth weight was 1,108 g, and multiple malformations were present. Chromosomal analysis demonstrated a karyotype of 69,XXY. At the time of this report, she lived at home and was 280 days old. A review of triploid infants revealed that the relatively unique clinical features of triploidy were syndactyly of the third and fourth fingers and abnormal erythrocyte indices. The associated karyotypes were 69,XXX and 69,XXY but not 69,XYY. Two of five infants died of pneumonia. Two infants, including the infant described herein, developed infantile spasms after the age of 200 days. Triploid infants with long-term survival are at high risk of developing pneumonia and infantile spasms.

Keyword : Erythrocyte indices; Fetal growth restriction; Long-term survivor; Syndactyly; Triploidy


Abstract in Chinese

Introduction

Triploidy is a chromosomal abnormality that occurs in 1% of pregnancies.1 Almost all triploid fetuses abort spontaneously in the first trimester; therefore, live-born triploid infants are rare.2-6 In addition, live-born triploid infants usually die soon after birth. We herein report a triploid infant who survived for more than 250 days and was discharged home. We also performed a review of the long-term survival of triploid infants to understand the relevant clinical features.

We obtained permission from the patient's parents to publish the features of this case.

Case Report

The infant's father was 43 years old and unrelated to the mother, who was 40 years old. The mother was 7 gravida, 1 para and had undergone 6 abortions (4 spontaneous abortions, 2 induced abortions). There was no significant family or medical history. Because severe fetal growth restriction was noted from 19 weeks of gestation, the infant was delivered at 33 weeks 4 days of gestation by cesarean section.

The birth weight was 1,108 g (below 1st percentile), length was 36.5 cm (below 1st percentile), and head circumference was 27.5 cm (just below 5th percentile). The Apgar score was 3 points at 1 minute and 6 points at 5 minutes. The infant had multiple external malformations including sparse eyebrows, blepharoptosis, bilateral syndactyly of the third and fourth fingers, bilateral overlapping of the third and fourth toes, and labial adhesions. The placenta weighed 360 g and had no cystic villi. A complete blood count obtained at birth showed that the mean corpuscular volume, mean corpuscular haemoglobin, and mean corpuscular haemoglobin concentration were 129.8 fL, 47.2 pg, and 36.4%, respectively. These three abnormal erythrocyte indices are reportedly increased in infants with triploidy.7 Bilateral colobomas were noted upon eye examination. Brain magnetic resonance imaging demonstrated brain atrophy (mainly in the frontal lobe) and agenesis of the corpus callosum; however, whole-body computed tomography and ultrasound scanning revealed no major congenital anomalies.

Chromosomal G-banding of peripheral blood samples demonstrated a karyotype of 69,XXY in all 100 cells analysed. Although a Y chromosome was detected, the external genitalia were female; therefore, we determined that the infant was female. We recommended a chromosomal analysis and further analysis of other tissues, including the buccal mucosa or skin; however, the parents did not grant approval.

The patient required intratracheal intubation and ventilator management for treatment of respiratory failure until the age of 21 days, and indomethacin was administered twice to manage a patent ductus arteriosus. Administration of intravenous glucose for hypoglycemia was necessary until the age of 55 days. She developed bacteremia caused by Enterobacter cloacae at 66 days, which resolved after antibiotic treatment. She was vaccinated after 90 days; however, she developed a high fever, poor general condition, and elevation of her C-reactive protein blood concentration soon after vaccination. Because she had mild apnea and a respiratory disorder, she required oxygen therapy until 148 days of age. Oral feeding was difficult to perform after a corrected age of 1 month; therefore, she required tube feeding. At the age of 222 days (corrected age of 5 months), she required no medical treatment except tube feeding and was discharged home.

At the age of 248 days, she was readmitted because of convulsive seizures. An electroencephalogram demonstrated an abnormal electrical pattern consistent with hypsarrhythmia; therefore, we diagnosed her with infantile spasms. Antiepileptic drugs were administered, and her seizures were gradually controlled. At the time of this report, she was 280 days old and still at home.

Discussion

Long-term survival (>150 days) of triploid infants is very rare. The clinical features of such triploid infants are reviewed in Table 1.2-6 All parents except those in the present case were <40 years of age. There are no characteristic antenatal features with which to diagnose triploidy during the fetal period. The features of live-born triploid infants are various; therefore, there are no absolute clinical findings of triploidy. Nevertheless, bilateral syndactyly of the third and fourth fingers is not often reported in other chromosome disorders.8 In addition, abnormal erythrocyte indices are unique to triploidy.7 These findings might be helpful for diagnosis.

The karyotype of triploid infants with long-term survival is 69,XXX or 69,XXY, but not 69,XYY. Some infants were diagnosed by analysis of both peripheral blood lymphocytes and skin; therefore, the infant described herein may have had mosaic triploidy. A previous report has described live-born mosaic triploid infants.9 In most such cases, triploid cells were not detected in the peripheral blood, but they could be detected using fibroblast cultures derived from the skin or bone. In the present case, triploidy was confirmed in all 100 blood cells tested; therefore, we assumed that she was a complete triploid infant. In cases involving investigation of the origin of the extra haploid set of chromosomes in triploidy, the extra set was of maternal origin in all infants. Such analysis was not performed in our case because the parents did not grant permission. However, we considered that the extra set of chromosomes was of maternal origin because the infant showed fetal growth restriction, a large head relative to body size, and no cystic villi in the placenta, which are all characteristics of maternal origin.1

Only six infants survived for >150 days, and the longest surviving infant was aged 312 days. Two of the five infants died of pneumonia. Our patient developed bacteremia and strong side effects of vaccination; therefore, triploidy might cause immune system dysfunction. We believe that adequate and rapid treatment of infection is important for long-term survival of triploid infants.

Seizures due to infantile spasms were reported in the longest surviving infant with triploidy.4 That infant and the present infant developed seizures at the age of 225 and 248 days, respectively; therefore, long-term survival might be associated with the development of infantile spasms after the age of 200 days.

In conclusion, our patient had similarities with previously described live-born triploid infants and showed the second-longest survival at the time of this report. Clinical findings of triploidy are difficult to diagnose in the fetal period and at birth; however, several unique features, including bilateral syndactyly of the third and fourth fingers and abnormal erythrocyte indices, might be useful for diagnosis. This disease has a poor prognosis, and very few infants live for >150 days. Prevention of infection (including pneumonia) and seizures caused by infantile spasms are important for long-term survival of triploid infants.

Table 1 Clinical features of long-term survival (>150 days) of triploid infants
Parameters Present case Am J Med
Genet 2008:2
Genet Mol Res
2005:3
Am J Med
Genet 1986:4
Acta Paediatr
Scand 1986:5
Ann Genet
1977:6
Mother age (years) 40 36 28 29 31 25
Father age (years) 43 36 28 31 33 26
Para 1 0 1 1 1 1
Family and past history No No No No No No
Antenatal features FGR FGR FGR
Oligohydramnios
No Subnormal
symphyseal-fundal length
No
Gestational age (weeks) 33 29 39 37 31 28
Birth weight (g) 1,108 566 1,850 1,417 700 1,450
Postnatal features
(main facial anomalies)
Blepharoptosis
Sprase
eyebrows
Hypertelorism
Blepharoptosis
Low-set ears
Micrognathia
Microstomia
Small palpebral
fissures
Low-set ears
Hypertelorism
Cleft lip and palate
Micrognathia
Hypertelorism
Low-set ears
Cleft lip,
alveolus
and palate
Hypertelorism
Bleopharoptosis
High-arched palate
Micrognathia
Postnatal features
(main limb anomalies)
Syndactyly of the
3rd and 4th
fingers (bilateral)
Overlapping of
the 3rd and 4th
toes (bilateral)
Syndactyly,
clinodactyly
and
camptodactyly
of fingers
Overlapping of the
3rd and 4th
fingers (bilateral)
Overlapping of
the 2nd and
3rd toes
(bilateral)
Syndactyly of
the 2nd and 3rd
fingers (unilateral)
Campylodactyly
and clinodactyly
of fingers (bilateral)
Bowed tibia (unilateral)
Rocker-bottom feet (bilateral)
Syndactyly of the
3rd and 4th
fingers (unilateral)
Overlapping
fingers
Clinodactyly and
camptodactyly
of fingers
Bowed tibia
Rocker-bottom feet
Karyotype 69,XXY 69,XXX 69,XXX 69,XXY 69,XXY 69,XXX
Tissues of choromosomal analysis Peripheral blood lymphocytes Peripheral blood lymphocytes Peripheral blood lymphocytes
Cord blood
Peripheral bloodlymphocytes
Skin
Peripheral blood
lymphocytes
Peripheral blood
lymphocytes
Skin
Origin of triploidy Not analysed Not analysed Not analysed Maternal Maternal Maternal
Discharge to home Yes (222 days) No Yes (15 days) Yes (22 days) No Yes (104 days)
Survival time > 280 days 221 days 164 days 312 days 27 weeks 23 weeks
Cause of death (Survival at the time of this report) Pulmonary hypertension progressed Cardiorespiratory problems Pneumonia Pneumonia Dyspnoea
FGR, fetal growth restriction

Disclosure Statement

All the authors declare that there is no conflict of interest.

Acknowledgment

We thank Angela Morben, DVM, ELS, from Edanz Group (www.edanzediting.com/ac), for editing a draft of this manuscript.


References

1. McFadden DE, Kalousek DK. Two different phenotypes of fetuses with chromosomal triploidy: correlation with parental origin of the extra haploid set. Am J Med Genet 1991;38:535-8.

2. Takabachi N, Nishimaki S, Omae M, et al. Long-term survival in a 69,XXX triploid premature infant. Am J Med Genet A 2008;146a:1618-21.

3. Iliopoulos D, Vassiliou G, Sekerli E, et al. Long survival in a 69,XXX triploid infant in Greece. Genet Mol Res 2005;4:755-9.

4. Sherard J, Bean C, Bove B, et al. Long survival in a 69,XXY triploid male. Am J Med Genet 1986;25:307-12.

5. Arvidsson CG, Hamberg H, Johnsson H, Myrdal U, Anneren G, Brun A. A boy with complete triploidy and unusually long survival. Acta Paediatr Scand 1986;75:507-10.

6. Cassidy SB, Whitworth T, Sanders D, Lorber CA, Engel E. Five month extrauterine survival in a female triploid (69,XXX) child. Ann Genet 1977;20:277-9.

7. Pai GS, Grush OC, Shuman C. Hematological abnormalities in triploidy. Am J Dis Child 1982;136:367-9.

8. Holmes LB. Common Malformations. New York: Oxford Universtiy Press, 2012.

9. Graham JM Jr, Hoehn H, Lin MS, Smith DW. Diploid-triploid mixoploidy: clinical and cytogenetic aspects. Pediatrics 1981;68:23-8.

 
 

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