Chromosomal Foetal and Placenta Abnormalities Associated with Exomphalos and Umbicinal Hernia-Juniper Publishers
Juniper Publishers-Journal of Pediatrics
Abstract
Exomphalos is a rare congenital disorder demonstrated
by failure of convergence mesoderm segments. Exomphalos is associated
with congenital malformations and chromosomal abnormalities of autosomal
or sex chromosomes and abnormalities with increased incidence in
various systems such as renal and cardiovascular. The morbidity and
mortality can be minimized by recognition of specific abnormalities
associated with exomphalos development, the corresponding management and
treatment strategies.
Conclusion: Exomphalos and umbilical
hernias’ may be associated with chromosomal abnormalities in autosomal
and sex chromosomes and are related with genetic syndromes such as
paternal uniparental disomy (UPD), Pallister-Killian (PKS) and
Beckwith-Wiedemann syndrome.
Keywords: Exomphalos; Umbicinal hernia; Chromosomal abnormalities; genetic syndromes; Abnormal karyotype
Introduction
Exomphalos separated in major and minor and could be
associated with limb abnormalities, renal defects or caudal midline
syndromes. Even though cardiac and renal defects are associated with the
occurrence of exomphalos the prevalence is not yet associated with
specific chromosomal abnormalities. Exomphalos may be associated with
chromosomal abnormalities of both autosomal and sex chromosomes and
other syndromes such paternal uni parental disomy (UPD), Pallister
Killian (PKS) syndrome Beckwith-Wiedemann syndrome and feto placental
chromosomal abnormalities (CMP). At this mini review study we will
analyze the combination of exomphalos and umbicinal hernia with specific
chromosomal abnormalities and genetic loci associated with the
syndromes development.
Umbicinal Hernia and Chromosomal Abnormalities of Autosomal Chromosomes
Umbicinal hernia and exophalos are rare congenital
conditions with an incidence of 2-3 cases per 10,000 newborns and are
associated with chromosomal abnormalities in foetus and placenta [1,2].
The risk of umbilical hernia and exomphalos varies according to
maternal age, gestational age, type of birth and genetic disorders [3,4].
Trisomes 13 and 18 are the most common chromosomal
abnormalities associated with the occurrence of umbilical hernia.
Snijders et al. [3]
determined the appearance of omphalocele in 22.5% of foetuses with
trisomy 18, 9.1% of foetuses with trisomy 13, 12.5% of foetuses with
other triploid chromosomal abnormalities while 0, 45% of embryos had no
chromosomal defects. According to literature the risk factors such as
Trisomes 18 or 13 in foetuses with omphalocele is 340 times higher
comparing with embryos with no exomphalos during 11th to 14th weeks of gestational age [5,6].
Chen et al. [7] in a study of 89 cases of trisomies 18 revealed 12 cases with omphalocele (13.48%) estimated male to female ratio of 2:1 [7].
Blazer et al studied 18 foetuses with omphalocele and diagnosed 11
cases (61.1%) with chromosomal abnormalities, most cases related to
trisomy 18, 21 and one case with fetal karyotype 45 X [6,7].
Calzolari et al. [1,2]
analyzed 160 embryos and found 94 cases of umbilical hernia (58.8%)
with concomitant chromosomal abnormalities. In 60 cases revealed
trisomies 18, 23 or 13, four cases with trisomy 21 and seven with other
chromosomal abnormalities [1,2].
Gilbert & Nicolaides [8]
studied of 35 foetuses with omphalocele found that 19 had a chromosomal
abnormality, 17 of them trisomy 18 and one karyotype 47 XXY [8]
while Brant berg in a study of 90 prenatally diagnosed omphalocele
revealed 44 cases with chromosomal abnormalities most of them with
trisomy 18, 13 and 21 [4,8].
Chromosomal abnormalities were found in majority of foetuses with
central and epigastria omphalocele. On the other hand, Van de Geijn
analyzed 22 foetuses with omphalocele and found 10 cases with autosomal
chromosomal abnormalities, six with trisomies 18 and one with trisomy 13
[8,9].
Hughes et al. [10]
studied 30 foetuses with omphalocele and found 13 cases who had
chromosomal abnormalities. Most of the foetuses had trisomy 18, trisomy
13, two had a trisomy 21 and one Turner syndrome while Hwang &
Kousseff [11]
in a study of 93 cases of umbilical hernia found in 37 cases with
chromosomal abnormalities, including trisomy 19, 18, 11, 21 and trisomy
13. Nicolaides et al. [6]
in a study of 116 foetal of omphalocele revealed 42 cases (36.2%) of
identified autosomal chromosomal abnormalities. Most of examined
foetuses had trisomy 18, six had trisomy 13 [12].
Additionally, Eydoux et al. [13]
in the one study of 46 embryos with omphalocele found that 12 cases
(26.1%) had chromosomal abnormalities and seven trisomy 18, trisomy 13
while Hsu et al. [14] studied 24 neonates with omphalocele and reveal six cases (25%) with chromosomal abnormalities such as trisomy 18 and 13 [14].
Even if several studies revealed the correlation between umbilical hernia and trisomy 21; Torfs et al. [15]
found only one case of trisomy 21 among 2979 newborns with omphalocele
and concluded that trisomy 21 is not predispose of increased risk for
umbilical hernia. Mastroiacovo et al. [16]
revealed seven cases of trisomy 21 among 8560 cases of umbilical
hernia. At this study the ratio was 1/1200 which was significantly
higher than 1 /425,000 of general population, suggesting that trisomy 21
increases the risk of umbilical hernia in fetus.
Umbicinal Hernia and Sex Chromosomal Abnormalities
Besides autosomal chromosome abnormalities exomphalos
and umbicinal hernia can also be associated with chromosomal
abnormalities of sex chromosomes such as monosomy 45 X and trisomies 47
XXY or 47 XXX [17-19].
In prenatal screening is important besides abnormalities of autosomal
chromosomes to identify chromosomal abnormalities of sex chromosomes as
possible key factors of umbilical hernia development.
Saller et al. [17] reported the presence of monosomy 45 X in a fetus with omphalocele while Govaerts et al. [18]
identified a case of umbilical hernia in fetus with monosome 45 X and
polyhydramnion by ultrasound analysis during gestational age of 22
weeks. Goldstein & Drugan [19]
suggested that umbilical hernia in patients with Turner syndrome may be
due to expression of some localized genes of X chromosome in early
pregnancy. Several reports suggested that chromosomal abnormalities are
more common in combination with omphalocele [20,21] while the cysts of umbilical cord increase risk of aneuploidy occurrence, mainly of trisomy 18 in fetuses with omphalocele [21]. Cysts umbilical related omphalocele usually are pseudo cysts and allantoid vesicles [21].
Syndrome Pallister-Killian (PKS) and Umbicinal Hernia
Pallister-Killian (PKS) Syndrome is a malformation
characterized by mosaicism and tetrasomia of 12p genetic region. The PKS
has the clinical features of local alopecia, severe mental retardation,
seizures and frequent occurrence of diaphragmatic hernia while in some
cases it may be associated with omphalocele. Tejada et al. [22]
have reported a case of PKS with ultrasonographic features such as
polyhydramnion, umbilical hernia and short length diagnosed with
tetrasomia of 12p confirmed in cell cultures of skin fibroblasts.
Paternal Uniparental Disomy (UPD) of Chromosome 14 and Umbicinal Hernia
Paternal uniparental disomy (UPD) has been reported
to be associated with multiple abnormalities such as thoracic
hypoplasia, ribs abnormalities, laryngomalacia, hypertrophic
cardiomyopathy and mental retardation [23]. Papenhausen et al. [24], Cotter et al. [25] and Kurosawa et al. [26]
reported the correlation of umbilical hernia with occurrence of UPD of
chromosome 14. Towner et al suggested that prenatal diagnosis of
abdominal defect associated with increased nuchal translucency or
skeletal abnormalities and coexistent of UPD of chromosome 14 [27].
Several abnormal characteristics are associated with
UPD on different chromosomes. For example, genetic mapping on chromosome
11 and paternal UPD connected to Beckwith Wiedemann syndrome [28,29]. UPD of chromosome 15 has also been associated with the syndromes Prader Willi and Angelman [30] as well as the UPD of chromosome 16 may also associate with abnormal phenotypes [31,32].
Micro duplication of Genetic Region 15q11
According to literature referred a case report of a
foetus with exomphalos, increased nuchal translucency and normal
karyotype. The ultrasound analysis revealed exomphalos with micrognathia
and tetralogy of Fallout. Although the karyotype was normal molecular
karyotype revealed micro duplication of 408 kb in chromosomal region of
15q11.2.
Beckwith-Wiedemann Syndrome (BWS) and Exomphalos
BWS caused by impairments and deficiencies occurred in the chromosomal region of 11p15 [33-35].
This genetic region comprises the genes involved in the cell cycle,
development and tumour suppression. The chromosomal location of 11p 15
is organized into two subareas comprising the genes 1GF2 and H19 and
another centromeric region includes genes CDKN1C (Kinase Inhibitor 1C),
KCNQ1 (subfamily Q, potassium voltage-gated channels) and KCNQ1OT1 [34,35].
Mutations in CDKN1C gene (known as p57Kip2) demonstrated at 5% of patients with BWS [36].
Patients with mutations CDKN1C gene have a typical phenotype of BWS,
with a very high frequency of exomphalos. The appearance of exomphalos
associated quite strongly with the syndrome as 65% of patients with BWS
may appear exomphalos [35,36].
Exomphalos occurrence is more frequent in patients
with mutations in the genes KCNQ1OT1 and CDKN1C. If methylation status
of KCNQ1OT1 and H19 genes is normal then sequencing analysis of CDKN1C
is important especially in patients with family history of exomphalos [35,36].
Fetoplacental Chromosomal Abnormalities (CMP) and Exomphalos Development
The effects of chromosomal abnormalities in placental
and foetus (CPM) are under investigation due to assess the
participation of these genetic elements in exomphalos development [37].
CPM aberrations associated with growth retardation, and foetal death.
The fetoplacental chromosomal abnormalities may lead to emergence of a
different number of chromosomes of placenta and the foetus even if the
karyotype is normal. These foetuses may reveal normal growth [38] or intrauterine growth restriction outcome that may result in intrauterine foetal death [39]. Drikos et al studied case of an infant diagnosed prenatally with exomphalos with intestinal contents from the 14th
week of gestational age. Prenatal diagnosis by choral villi sample
detected pseudomosaicism of placenta (mos45X/46XY), while amniocentesis
on the 19th week of pregnancy revealed normal karyotype. This
is the first reported case of placental pseudo-mosaicism (mos45X/46XY)
combined with exomphalos [38].
Trisomy 2 of the placenta associated with growth
retardation and abnormal clinical characteristics at birth, while the
CPM on the sex chromosomes does not usually have any adverse effect on
embryo development [39].
The pseudo-mosaicism of placenta may also be associated with the
occurrence of umbilical hernia and various phenotypic abnormalities. In a
clinical case showed non mosaic trisomy 22 in the chorionic villus,
mosaic trisomy 22 in amniocytes and normal karyotype of lymphocytes
showed abnormal foetal characteristics of reminiscent Goldenhar
syndrome. The foetal mosaicism appears to be the likely explanation for
Goldenhar syndrome [39,40].
Conclusion
Exomphalos and umbicinal hernia can quite often
associate with disorders of the gastrointestinal and central nervous
system seems to be predominated such as in cases of Beckwith- Wiedemann
and abnormal karyotype syndromes.
Exomphalos may be associated with limb abnormalities
or caudal midline syndromes. Although cardiac and renal abnormalities
seem to be associated with the occurrence of exomphalos the prevalence
is not apparently associated with chromosomal abnormalities. Such
disorders may be associated with chromosomal defects at autosomal and
sex chromosomes and other syndromes such as paternal uniparental disomy
(UPD), Pallister-Killian (PKS) and Beckwith-Wiedemann syndromes. The
determination of the associated malformations can lead to conscious
prenatal counselling. This provides parents reliable and clear
information's in order to determine the continuation of pregnancy.
Compliance with Ethical Standards
Funding: This mini review has been written without support of any fund.
Disclosure of Potential Conflicts of Interest
The author declares have no conflict of interest.
For more articles in Academic Journal of
Pediatrics & Neonatology please click on:
https://juniperpublishers.com/ajpn/index.php
https://juniperpublishers.com/ajpn/index.php
Comments
Post a Comment