Paediatrica Indonesiana p-ISSN 0030-9311.
e-ISSN 2338-476X.
Vol.
No.
350-6 .
DOI: https://doi.
org/10.
14238/pi65.
Case Report Edwards Syndrome and Trisomy 8:
a case report of a newborn with multiple congenital anomalies with double aneuploidy Agustini Utari1.
Nani Maharani2.
Rita Indriyati2.
Nydia Rena Benita Sihombing2.
Gatot Irawan Sarosa1.
Tri Indah Winarni2 Chromosomal aneuploidy is the most common genetic cause of multiple congenital anomalies (MCA), contributing to high neonatal mortality and morbidity rates in intensive care units.
Prevalence of live birth double trisomy is rarely reported, with previous studies reporting the involvement of autosomal aneuploidy combined with sex chromosomal aneuploidy that is a more tolerable or benign phenotype.
Mostly, a live-born baby with a double trisomy is associated with mosaicism.
This report aims to present a rare case of a viable baby with non-mosaic double autosomal trisomy involving chromosomes 8 and 18.
A term baby from advanced maternal and paternal age with low birth weight and height was born from spontaneous vaginal delivery from unremarkable pregnancy.
The phenotype was suitable with Edward syndrome with congenital heart anomalies confirmed by cytogenetic analysis with additional extra chromosome 8 .
XX, 8, .
The baby was on and off the mechanical ventilator due to respiratory failures, and her health condition gradually deteriorated, leading to her death at the age of 2.
5 months due to neonatal pneumonia.
[Paediatr Indones.
65:164-70.
DOI: https://doi.
org/10.
164-70 ].
Keywords: double trisomy.
multiple abnormalities.
rare diseases ouble aneuploidy in a newborn baby is very rare because it is presumed not viable in most cases due to multiple organ anomalies, called multiple congenital anomalies (MCA).
The most common genetic cause of MCAs are chromosomal and single-gene disorders, chromosomal abnormalities .
tructural and numerica.
were found in approximately 40% of cases.
1 Previous studies reported as much as 50% of cases were related to genetic disorders.
2,3 There was a wide variation in the incidence over time and between countries .
% to 36.
6%), reflecting multiple 350 A Paediatr Indones.
Vol.
No.
March 2025 factors that may contribute to the incidence such as healthcare providersAo knowledge and awareness, healthcare facilities .
o detect prenatally and possibility to do terminatio.
, socio-cultural and religious beliefs, control of infection, and nutritional Neonates with MCA contribute considerably to the mortality rate .
%) in neonatal intensive care units (NICU).
2 Previous live-born cases have been reported involving sex chromosomes combined with autosomal aneuploidy, mostly trisomy 13, 18, or 21.
7,8 Extra sex chromosomes are more tolerable in humans than autosomal trisomies, and sex chromosome trisomies are generally benign.
primarily affects sexual development and fertility, but they often have normal life spans, while autosomal aneuploidy is mostly deleterious.
9 Rare autosomal trisomies (RAT.
are chromosomal trisomies besides involving chromosomes 13, 18, 21.
X, and Y, in complete/non-mosaic form.
RATs are usually lethal From the Department of Pediatrics.
Faculty of Medicine.
Universitas Diponegoro/Dr.
Kariadi General Hospital1 and Center for Biomedical Research (CEBIOR).
Faculty of Medicine.
Universitas Diponegoro2.
Semarang.
Central Java.
Indonesia.
Corresponding author: Tri Indah Winarni.
Center for Biomedical Research (CEBIOR).
Faculty of Medicine.
Universitas Diponegoro.
Jl.
Prof.
Mr.
Soenario.
Tembalang.
Semarang .
Central Java.
Indonesia.
Telp.
62 24 8454714.
Email: triindahw@gmail.
com OR triwinarni@ Submitted March 26, 2023.
Accepted January 3, 2025.
Agustini Utari et al.
: Edwards Syndrome and Trisomy 8: a case report of a newborn with multiple congenital anomalies with double aneuploidy or not compatible with life and they have therefore infrequently been found as a result of invasive prenatal diagnosis from amniotic fluid or chorionic villus cells.
While, in mosaic form.
RAT has been linked with fetal death, stillbirth, intrauterine growth restriction (IUGR).
MCA, and minimally affected individuals.
In principle, a RAT is only viable when present in mosaic state.
The origin of numerical chromosomal abnormalities/aneuploidy are meiotic and mitotic Failure of homolog chromosomes to segregate properly to opposite poles during telophase, called meiotic non-disjunction, results in the production of gamete with improper chromosome number in complete form.
When a normal gamete combines with a gamete with an extra chromosome, resulting a trisomy zygote.
11 Predominantly in female meiosis, although there is discrepancy among different chromosomes, these increase exponentially in women over the age of 35 years, called advanced maternal 12 Postzygotic mitotic non-disjunction .
rror in chromosome segregation during mitosi.
during early embryonic development accounted as the origin of mosaic form.
We present a live-born baby with multiple congenital anomalies suspected to have Edward syndrome with double autosomal trisomies .
XX, 8, .
The case A female baby was born at term to a 41-year-old gravida 3, para 2, abortus 0 mother from an unremarkable pregnancy and advanced paternal age .
-year-ol.
She was delivered with spontaneous vaginal delivery, her weight was 1700 g, the birth length was 42 cm (< 3rd centil.
, microcephaly (<3rd centil.
, and birth asphyxia (Figure .
Physical examination showed microcephaly, microphthalmia, hypertelorism, a depressed nasal bridge, low-set ear, micro-retrognathia, and high-arched palate.
The sternum was short with pectus excavatum, wide set nipple, and the heart examination presented a systolic murmur.
No liver and spleen enlargement.
Genitalia was a typical female.
The extremities examination showed clenched hands with overlapping fingers, single palmar transverse crease, prominent calcaneus, and talipes equinovarus.
Figure 1.
Patients at 1-month-old.
Note: microphthalmia, depressed nasal bridge, low set ear, micrognathia, and short sternum Paediatr Indones.
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65 No.
March 2025 A 351 Agustini Utari et al.
: Edwards Syndrome and Trisomy 8: a case report of a newborn with multiple congenital anomalies with double aneuploidy She had mild hyponatremia .
-135mmol/L, reference: 136-145mmol/L).
An Echocardiogram demonstrated a moderate perimembranous ventricular septal defect and a small secundum atrial septal defect (ASD II).
A cranial ultrasound revealed no intraventricular hemorrhagic and no enlargement in the ventricles.
Renal ultrasound was unremarkable.
Laboratory evaluation showed hemoglobin level was 8.
9 g/dL.
Cytogenetic analysis showed a karyotype of 48 XX, 8, 18 (Figure .
She was admitted to the neonatal intensive care unit on 2nd day after birth and used a mechanical ventilator for two weeks due to poor respiratory effort, and she has been on and off the mechanical ventilator since then.
She also had a problem with frequent vomiting, neonatal jaundice, anemia, and pneumonia.
Her clinical course was marked by multiple organ The first resuscitation was succeeded in the last hospitalization in the pediatric intensive care Parents were educated regarding their childAos condition and the prognosis.
subsequently, the parent was made a do not resuscitate (DNR) decision.
She died at 2.
5 months of age due to neonatal Clinical characteristics of this patient are in concordance with Edwards syndrome and Trisomy 8, with the details listed in Table 1.
Discussions We presented, to the best of our knowledge, the first liveborn baby with double aneuploidy of chromosomes 18 and 8 worldwide.
Another double aneuploidy of autosomes was reported in a previous study which found trisomy 7 and 8 from a case of spontaneous The case was born from advanced maternal and paternal age.
In most cases, advanced maternal age is the most common risk factor for meiosis nondisjunction, the origin of numerical abnormalities called aneuploidy.
15 Chromosome segregation errors in meiotic I due to premature centromere division and defective spindle assembly checkpoint at meiosis I increase dramatically in women age, from around 2-3% in a woman in her 20s and dramatically increases to about 35% in a woman in her 40s.
12,15,16 However, the origin of autosomal aneuploidy specific patterns Trisomy 18, called Edwards syndrome, is the second most common type of aneuploidy, with a prevalence of 1 in 2,000 to 8,000 live births and a male-female ratio of 5:1.
17-19 Most human aneuploidies found in embryos originate from the 20,21 In the previous parental study, the maternal origin was 95%, and the remaining cases were Figure 2.
Karyotype revealed double trisomy .
XX, 8, .
352 A Paediatr Indones.
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: Edwards Syndrome and Trisomy 8: a case report of a newborn with multiple congenital anomalies with double aneuploidy Table 1.
Clinical characteristics of case according to trisomy 8 and 18 Clinical characteristics Trisomy 8 Trisomy 18 Our Case Hypotonia Seizure N/A Microcephaly Prominent occiput Triangular Face Asymmetric face Microphthalmia Neurological anomalies Poor sucking Developmental delay Craniofacial anomalies Prominent forehead Deeply set eyes Hypertelorism Epicanthal folds Micro-retrognathia Incomplete dental occlusion Cleft lip and palate N/A High palate Small and triangular mouth Small mouth Downturn mouth Shallow philtrum Prominent malar bone Microtia Thickened helix Deep conchae Low set ear Strabismus Ear dysplasia Hypoplastic nasal root Prominent nasal bridge Broad nasal bridge Upturn nose/everted nostril Choanal atresia Low anterior hairline N/A Musculoskeletal anomalies Severe growth retardation Generalized atrophy Short stature Short neck Webbed neck Short sternum Pectus excavatum Barrel chest Paediatr Indones.
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: Edwards Syndrome and Trisomy 8: a case report of a newborn with multiple congenital anomalies with double aneuploidy Table 1.
Clinical characteristics of case according to trisomy 8 and 18 .
Clinical characteristics Trisomy 18
Our Case
Wide set nipple Clench hand with overriding fingers Rocker bottom feet with prominent calcaneus
Deep plantar creases Trisomy 8
Talipes equinovarus
N/A
Joint contracture Kyphoscoliosis Absent/dysplastic patella
N/A
Generalized osteoporosis Cardiovascular anomalies Ventricular septal defect Atrial septal defect Patent ductus arteriosus Tetralogy of Fallot Pulmonary hypoplasia Laryngomalacia Omphalocele Atresia esophageal Pyloric stenosis Umbilical hernia Horseshoe kidney Renal agenesis Clitoral hypertropia Pulmonary anomalies Gastrointestinal anomalies Genitourinary anomalies Central nervous system anomalies Hydrocephalus Corpus callosum hyperplasia paternal origin.
22 Meiosis II non-disjunction error is the predominant mechanism of trisomy 18, where advanced maternal age is the jeopardy.
23 The average lifespan for infants with trisomy 18 is three days to two 5-38% survive for three months.
24 Survival rate is greatly affected by trisomy 18.
only 10% of cases with this condition will survive beyond the first year of life because it involves multiple organs and systems.
25 The main clinical characteristics of Edwards syndrome are mostly observed in this case, which are developmental delay, congenital heart disease, growth retardation, microcephaly, triangular and asymmetric face, microphthalmia, hypertelorism, low set ears, prominent nasal bridge, upturned nose, 354 A Paediatr Indones.
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Trisomy 8 is a rare condition, comprising 0.
of spontaneous abortions.
27 In live-born, trisomy 8 is almost always associated with mosaicism.
Non-mosaic cases, trisomy 8 cases mostly lead to adverse pregnancy outcomes from pregnancy loss to spontaneous 28 In most spontaneous abortion cases, the additional chromosome was due to maternal meiosis non-disjunction, while a post-zygotic mitotic gain of the additional chromosome was molecularly proven in liveborn cases.
23,28 Individuals with complete trisomy 8 are considered fatal.
thus, individuals in whom an Agustini Utari et al.
: Edwards Syndrome and Trisomy 8: a case report of a newborn with multiple congenital anomalies with double aneuploidy extra chromosome 8 is believed to be always mosaic In the absence of serious malformations, the survival rate is considered high.
Trisomy 8 mosaicism (T8M), called Warkany syndrome 2 is an enormously infrequent chromosomal abnormality in newborn babies with a prevalence of approximately 1: 25,000-50,000.
19 Characteristics of T8M are also extremely variable ranging from severe congenital malformations such as skeletal abnormalities .
rincipally vertebral and costal alteration.
, facial dysmorphisms, typically deep palmar and plantar creases, and developmental delay/intellectual disability to minute dysmorphic or normal individuals,29 thus, this condition often goes undiagnosed.
Identifying cases of partial or complete trisomy 8 mosaicism using lymphocytes of peripheral blood conventional karyotyping is very challenging.
in most cases, alteration is only found in fibroblasts.
30 In our case, we found trisomy 8 from the peripheral blood lymphocytes using conventional karyotyping.
Aneuploidy in the resulting egg and embryo leads to adverse pregnancy outcomes ranging from pregnancy loss, stillbirth, and multiple congenital anomalies or neonatal mortality.
31 The earlier pregnancy loss, the higher the rate of the chromosomal only approximately 10% of aneuploidy embryos will reach Ou 20 weeks of pregnancy and be born with MCA, stillbirth, or neonatal death.
32 Chromosomal testing is still an option to confirm aneuploidy in a patient with MCA, especially in limited-resources Double trisomy is a very rare chromosomal aberration that may cause adverse pregnancy outcomes from pregnancy loss to live birth babies with MCA, and the origin of additional autosomal aneuploidy is a specific pattern.
Limitation of study.
Diagnosis was done using conventional karyotype, in which the low level of mosaicism may not be detected.
Fluorescent in situ hybridization (FISH) can be used and successfully identify a low level of mosaicism.
Although very rare, this case shows that numerical chromosomal abnormalities may involve more than one autosome, called double trisomies, especially in children with major congenital abnormalities.
Care should be taken to ensure other aneuploidy is not Conflict of interest None declared.
Funding acknowlegment This work was supported by World Class Research University grant from Universitas Diponegoro [No.
118-02/UN7.
1/PP/2.
References