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.