Discussion:
HPE is a rare complex congenital malformation occurring in the human
brain during organogenesis due to a failure in dividing the
prosencephalon into right and left hemispheres completely or
partially3-6,8,10, which causes a group of
craniofacial anomalies.5 There are three levels of HPE
depending on the severity of the case: Lobar, characterized by the
separation of the left and right ventricles with a degree of frontal
cortical continuity, semi-labor where there is an incomplete separation,
and alobar where the interhemispheric fissure is absent there is only
one cerebral ventricle.10 The alobar HPE is considered
the most severe form due to its manifestation which also includes:
undifferentiated cerebral hemispheres, a thalamic
fusion2,4, a missing corpus callosum, no olfactory
nerves or optic tracts4, and
cyclopia.8 The last is the rarest and most severe
facial expression of alobar HPE.1,3,7 Cyclopia is
defined by the fusion of two optic grooves1 as a
result of the embryonic prosencephalon’s improper division of the eye’s
orbits into two cavities.3,6,7 Cyclopia itself is
always an outward sign of a profound brain
abnormality.4 The term “cyclopia” refers to
anarchist giant shepherds that had a single round eye in their front in
Greek mythology.8 The prevalence of newborns with
cyclopia, including stillbirths, is 1.05 per 100,000 live
births.1 This congenital condition occurs during
embryonic development, which typically happens between the 18th and 28th
day of gestation1,6,7, and there is a preponderance of
female babies.7,8 In our case, it was a male
stillborn. This congenital condition occurs during embryonic
development, which typically happens between the 18th and 28th day of
gestation1,6,7, and there is a preponderance of female
babies.7,8 The etiology of this condition is still
unknown exactly.1,2,7,9 Due to the embryonic forebrain
and mid-face both deriving from the prechordal mesoderm, several facial
malformations are typically linked, along with several other
defects.10 Despite the limitation of evidence, the
Sonic Hedgehog (SHH) gene regulator was revealed to be involved in the
division of the single eye field into two bilateral fields, so when
mutations cause SHH muting, the result will be cyclopia and there is a
fusion of the eye in the middle of the face.3,6,8Multiple heterogeneous risk factors are related. Both genetic and
environmental factors are the possible culprits including teratogenic
medication exposure during pregnancy (anticonvulsants, aspirin, retinoic
acid, aspirin, lithium), maternal diabetes, alcohol consumption,
infections like toxoplasmosis, rubella, cytomegalovirus, and herpes
simplex (TORCH), and chromosomal defects1,2,6-9.
However, in this presented case, no risk factors could be observed.
Alobar HPE is associated with many syndromes such as Smith-Lemli-Opitz
Syndrome (SLOS), Pallister-Hall Syndrome, and Trisomy 13 ‘Patau
Syndrome’2,3,10, which is the most common cause of
HPE.10 The facial deformities associated with alobar
HPE may include cyclopia, a single orbit with a median single eye, or a
partly split eye6,10. The nose is either absent
completely or replaced with a proboscis as a non-functioning
nose1,3,7,10. Typically, such a proboscis is observed
on the back or above the central eye and is a defining feature of a form
of cyclopia known as rhinocephaly or rhinencephaly.1Missing philtrum, otocephaly, astomia or microstomia also could be
found.6 In our case, we found the typical facial
features of cyclopia include: a median single orbit, the absence of a
nose, and a proboscis above the eye (Fig. 2). The presence of
extra-facial deformities like polydactyly, renal dysplasia,
omphalocele6-8, ventricular septal defects, and
myelomeningocele reported in other literatures.10 Only
polydactyly in the left foot could be observed in our dead fetus (Fig.
3). During the first trimester, the US can reveal distinctive images
that make it the most helpful investigation for diagnosing
cyclopia.1,2,4,6,7,9 After the third or fourth week of
pregnancy, the US can typically detect clear indications of cyclopia or
other forms of holoprosencephaly.1 In most cases that
were reported, the anomaly was detected early during the anomaly
scan.2 When HPE is suspected by the US, careful
intrauterine scanning of the fetus’s face can lead to a more accurate
diagnosis.4 However, the usual US may not detect
certain features that are useful in diagnosis7, thus
obtaining more information about the development of brain structures is
possible through in-utero magnetic resonance imaging
(MRI)4 or high-resolution MRI
scans.7 However, in our case, the woman never had any
prenatal care and the anomaly was only discovered after the fetus was
miscarried. The survival rate is extremely low in this
condition10 and the prognosis depends on brain fusion
degree, malformation, and complications.2,4 In cases
of lobar HPE, children can survive for several years with neurological
and mental challenges. Alobar and semi-labor HPE have been associated
with the worst prognosis2 and are not compatible with
life.2,4,7 Generally, the result will be a miscarriage
or a stillborn, and even if a child is born alive, it dies within hours
after birth.2,3,6,7 The fetus in our case, presented
with the alobar form of HPE associated with cyclopia (Fig. 1), Without
being genetically tested after the medical expulsion. In all cases,
termination of the pregnancy should always be offered as an option for
management. This procedure follows a comprehensive prenatal examination
and relevant genetic counseling, owing to the severity of the defects.
Further aids in the diagnosis of cyclopia include postnatal chromosomal
analysis and gross examination of the specimen.6,10There is no currently known treatment for this condition, and there is
no way to prevent it.8 This report emphasizes the
importance of prenatal check-ups, particularly in developing countries,
and the significance of early ultrasound diagnosis for gestation
termination and maternal psychological trauma prevention.