Extended survival of a premature infant with a postnatal diagnosis of complete triploidy

  1. Rachel Walsh and
  2. Anand Sharma
  1. Department of Neonatology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
  1. Correspondence to Dr Rachel Walsh; rachelwalsh1@nhs.net

Publication history

Accepted:06 Jan 2022
First published:07 Feb 2022
Online issue publication:07 Feb 2022

Case reports

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Abstract

Triploidy is a common chromosomal abnormality that usually results in spontaneous abortion. Liveborn infants usually die within hours or days of birth. We present the case of a female infant born at 30 weeks and 5 days of gestation who received a late postnatal diagnosis of complete triploidy. She had severe intrauterine growth restriction and postnatal findings of multiple facial and limb anomalies. Genetic testing was sent shortly after birth, and the baby had an uneventful neonatal admission, requiring low-level respiratory and feeding support. Following a diagnosis of complete triploidy, she was transferred to a hospice and died on day 36 of life. There are currently 12 other reported cases of survival beyond 30 days. This case adds to the known cohort and highlights the importance of genetic testing in premature neonates with congenital anomalies in order to guide ceiling of care discussions and advocate for quality of life.

Background

Triploidy is a common chromosomal abnormality in the first trimester of pregnancy and occurs in around 1% of all conceptions.1 2 It is characterised by an extra set of haploid chromosomes, resulting in a 69,XXX, 69,XXY or 69,XYY karyotype. Triploidy usually results in spontaneous abortion. The estimated prevalence of triploidy at 16–20 weeks’ gestation is 1 in 5000,2 and among live births, this is reduced to 1 in 10 000.3–5 Liveborn infants usually die early in the neonatal period, within hours or a few days of birth.4

We present the case of a female infant with a 69,XXX karyotype who was cared for on the neonatal unit until 34 days of age before being moved to a local hospice at the wishes of her family. She died at 36 days of age.

This case is important because it highlights the importance of timely genetic investigations. In the context of a preterm baby receiving intensive care, prolonged survival in this case did not exclude a diagnosis that would usually be incompatible with life. Identification of such conditions will allow clinical teams to carefully consider the ceiling of care and appropriate longer term management. With an accurate diagnosis, we can advocate for the baby and limit painful interventions or futile medical and surgical treatment.

Case presentation

Antenatal background

This infant was the second child born to non-consanguineous parents. There was no significant family history of note. Antenatally, a fetal echocardiogram and MRI revealed a very small fetus with disproportionately small body to head but no structural abnormality. The forehead was noted to be prominent, and there was an increase in the extra-axial cerebrospinal fluid space. Prior to delivery, the mother received a complete course of antenatal steroids.

The infant was delivered by elective caesarean section at 30 weeks and 5 days gestation due to severe intrauterine growth restriction (IUGR) and oligohydramnios. Her birth weight was 610 g (just below the 0.4th centile on the female UK WHO growth chart). Her head circumference was difficult to measure due to an unusual head shape. The median of successive head circumferences plotted on the 0.4th centile.

Clinical course

The baby was born in reasonable condition with a heart rate above 100 beats per minute and spontaneous respiratory effort by 1.5 minutes of life. She required non-invasive intermittent positive pressure ventilation in the delivery room and received surfactant via the less invasive surfactant administration (LISA) technique. She was transferred to the neonatal unit on non-invasive bilevel ventilation.

On full examination, the baby was found to have a number of dysmorphic features. These had not been anticipated antenatally and no antenatal genetic testing had been carried out. Significant findings were: partial syndactly of the digits on the right hand, syndactyly of the third and fourth fingers on the left hand, syndactyly of the second and third toes bilaterally and overlapping of the fourth and fifth toes bilaterally. She was noted to have large anterior and posterior fontanelles and ridged cranial sutures. She also had a flattened nasal bridge and prominent forehead.

Other than significant IUGR, the baby made good progress on the neonatal unit and had a relatively unremarkable course. She required non-invasive continuous positive airway pressure for 2 days before being weaned to heated humidified high flow oxygen therapy, which she continued to need at a rate of 2 L per minute until her discharge. Her oxygen requirement was approximately 30%–40%.

She did not display any cardiovascular instability, and echocardiography revealed a large patent ductus arterious but no other structural abnormality. Renal and cranial ultrasound scans were also normal during her admission.

In addition, the baby was treated for physiological jaundice with phototherapy. This later progressed to prolonged, conjugated jaundice. She was also anaemic and required one blood transfusion during her admission. The baby was noted to have impaired renal function with a persistent mild elevation in urea, creatinine and sodium despite being well hydrated. The hypernatraemia persisted following resolution of the elevated urea and creatinine. She had no significant hypoglycaemia.

Growth and nutrition

The baby was commenced on parenteral nutrition after birth and gradually established enteral feeding as would be the normal protocol for a premature infant of her size. Full enteral feeds via nasogastric tube were achieved by day 8 of life. Despite adequate nutrition, growth was very poor, and her weight was close to static. Weight on day 31 of life was only 110 g above birth weight and had dropped to >4 SD below the 0.4th centile. Head growth may not have been accurately recorded due to the unusual shape and suspicion of craniosynostosis. However, this appeared to have remained on the 0.4th centile by day 31 of life.

Investigations

During her admission, this infant was screened for prolonged, conjugated jaundice. The results of this screen were unremarkable other than increased excretion of several amino acids in her urine amino acids profile. This was of uncertain significance. Hepatitis serology was negative. Ultrasound imaging revealed normal intracranial appearances as well as normal kidneys, liver and bladder. A chest X-ray demonstrated clear lung fields but unusual modelling of the thoracic vertebrae. This can be associated with a skeletal dysplasia but there was no other evidence of this.

Differential diagnosis

Although the baby made good medical progress, the combination of severe IUGR and multiple dysmorphic features raised the suspicion of an underlying unifying disorder. Referral to genetics was instigated on day 2 of life and peripheral blood and buccal cells were sent for single nucleotide polymorphism (SNP) array and fluorescence in situ hybridisation testing.

On day 18 of life, a result was returned confirming triploidy. SNP array revealed arr[hg19]15q11.2 (22750305_23702085)x1,(1–22,X)x3. This described an extra haploid set of all chromosomes, consistent with triploidy, as well as a loss of approximately 952 Kb in the proximal long arm of chromosome 15 (locus q11.2). This loss is unrelated to the triploidy but is otherwise known to be associated with delayed speech and motor development, dysmorphism and behavioural problems.6 This was believed to be an incidental finding in this case.

Outcome and follow-up

Following genetic diagnosis, the baby was transferred to hospice care at the request of her parents. She was transferred on day 34 of life and died 2 days later. The specific circumstances of death are not given.

Discussion

Triploidy occurs by three distinct mechanisms: the fertilisation of a haploid egg by two haploid sperm cells, the fertilisation of a haploid egg by a diploid sperm cell or the fertilisation of a diploid egg by a haploid sperm cell.1 Normal gametes are haploid cells, but a diploid cell may be produced due to meiotic non-dysjuntion or other errors in germ cell precursors.

There are currently 12 reported cases of ‘long term survival’ (more than 30 postnatal days) in infants with triploidy.3 4 7–16 See table 1 for full details of the previously published cases. Our case brings this number to 13. Of the previously reported cases, the shortest survival time was 45 days. The female child we present survived until 34 days of age. However, literature review does not reveal any additional cases surviving for more than a number of hours following birth.

Table 1

Clinical features of infants with triploid surviving past 30 days of age

Karyotype Gestation at delivery (weeks) Sex Mode of delivery Weight Head circumference Facial features Limb features Other features Survival Cause of death Highest level care Phenotype
Weight in grams. Head circumference in centimetres. Growth centiles not given as not comparable between countries of publication.
Fryns et al7 69,XXX Term (weeks not given) F Caesarean 1810 g 32.7 cm Broad forehead, flattened nasal bridge, micropthalmia, microstmia and low set ears. Rocker bottom feet, tibial bowing, camptodactyly and clinodactyly. Hypoglycaemia and streak ovaries. 2 months Cachexia Nasogastric (NG) feeding support II
Cassidy et al8 69,XXX Unknown F Caesarean 1450 g 34 cm Hypertelorism, blepharoptosis, high arched palate and micrognathia Clinodactyly, camptodactyly, overlapping fingers, bowed tibia and rocker bottom feet. Unknown 160 days Respiratory failure Unknown II
Schrocksnadel et al
9		 69,XXX Unknown F Unknown Unknown Unknown Hypertelorism, low-set ears and high arched palate Syndactyly bilaterally fingers and toes. Polydactyly right foot. Left-sided haemihypertrophy. Seizures and diffuse cortical atrophy. 210 days Pneumonia Unknown Not given
Faix et al10 69,XXX 37 M Caesarean 1020 g Unknown Unknown Unknown Unknown 127 days Unknown Unknown Not given
Strobel and Brandt11 69,XXX 32 F Caesarean 890 g Unknown Unknown Unknown Unknown >5.5 months Unknown Unknown Not given
Arvidsson et al12 69,XXY 31 M Caesarean 700 g Unknown Hypertelorism, low set ears and cleft lip and palate Syndactyly of the third and fourth fingers unilaterally Hypotonia, absent suck, atrial septal defect (ASD) and cardiac myxomatous hamartomas. 27 weeks Pneumonia and cardiac failure NG feeding II
Sherard et al3 69,XXY 37 M Caesarean 1417 g 30.5 cm Prominent occiput, triangular-shaped face, hypertelorism, cleft lip and palate, micrognathia and abnormal ear shape. Fixed flexion of the wrists, ulnar deviation of hands, syndactyly, camptodactyly, clinodactyly, tibial bowing and rocker bottom feet. Ventricular septal defect (VSD) and seizures. 312 days Pneumonia and cardiac failure 1 day oxygen, ongoing NG feeds, discharged day 22. II
Niemann-Seyde et al13 69,XXX 34 F Caesarean 800 g 26.5 cm Unknown Unknown Unknown 74 days Unknown Unknown I
Hasegawa et al4 69,XXX 31 F Caesarean 650 g 26 cm Blepharophimosis, microphthalmia, hypertelorism, low-set and malformed ears and micrognathia. Syndactyly of fingers and toes. Funnel chest, absent bilateral fifth ribs, mild ventricular enlargement, hypoplastic thymus and ovaries. 46 days Pneumonia Ventilated II
Illiopoulos et al14 69,XXX 39 F Caesarean 1850 g 30.2 cm Small palpebral fissures, large fontanelles, low set ears, flat nasal bridge and small tongue. Hexadactyly right hand, single palmar creases and overlapping fingers and toes Seizures, absent corpus callosum, partial aplasia occipital lobe and dilated subarachnoid space. 164 days Cardiorespiratory deterioration Support only. Discharged home day 15. II
Takabachi et al15 69,XXX 29+5 F Caesarean 566 g 24 cm Frontal bossing, hypertelorism, blepharophimosis, micrognathia and low set ears. Clinodactyly, camptodactyly and malpositioned fingers, Bell-shaped thorax, atrial septal defect (ASD), ventricular septal defect (VSD) and pulmonary hypertension 221 days Pulmonary hypertension Ventilated and (parenteral nutrition) PN dependent. II
Hashimoto et al16 69,XXY 33 F Caesarean 1108 g Unknown Blepharoptosis, colobomas and sparse eyebrows Syndactyly of third and fourth fingers, overlapping toes Agenesis of corpus callosum, abnormal erythrocyte indices Over 280 days Survival at time of publication Ventilated 21 days. Indomethacin for PDA. II
This case 69,XXX 30+5 F Caesarean 610 g Unknown Flattened nasal bridge and
prominent forehead		 Syndactyly of the third and fourth fingers, syndactyly of second and third toes bilaterally and overlapping of the fourth and fifth toes bilaterally. Large anterior and posterior fontanelles and ridged cranial sutures. 36 days Respiratory deterioration failure to thrive Non-invasive ventilation and parenteral nutrition in first week of life. Presumed II

Ethics statements

Patient consent for publication

Acknowledgments

Dr Michael Parker (Consultant Clinical Geneticist at Sheffield Children’s Hospital) provided clinical advice and support during the admission of the baby as well as in the early stages of preparing this case report.

Footnotes

  • Contributors AS was the consultant neonatologist caring for this infant during her admission to the neonatal unit. RW is a senior neonatal grid trainee and was among the registrars caring for this infant during her admission. AS suggested a literature review when the infant was diagnosed. This was conducted by RW and revealed a very small number of children surviving beyond the hours and early days post birth. AS and RW agreed to write the case up as a case report due to its importance regarding end-of-life care. AS approached the parents in a follow-up bereavement clinic appointment, and they gave consent for a case report. The case report was written predominantly by RW with edits and input from AS.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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