Cyclopia, a newborn with a single eye, a rare but lethal congenital anomaly: A case report

Abstract

Introduction and importance
Cyclopia is a rare congenital disorder characterized by facial abnormalities. In this condition, the orbits of the eye are not properly divided into two cavities so that they can be seen either as a single eye field or two bilateral fields that are very close to each other. This syndrome affects the embryos that are either aborted or stillborn upon delivery or, at best, die shortly after birth.

Case presentation
This case report is of a 37-week- and 5-day-old female fetus with a birth weight of 2300 g, a height of 43 cm, and a head circumference of 31 cm. She was born to a 44-year-old mother through normal vaginal delivery at Mahzad Hospital, Urmia, Iran. In the physical examination, an eye and a 4-cm proboscis were seen in the middle of the forehead. The newborn also had no nose, and his outer ears were normal. No cleft lip or cleft palate was observed. Unfortunately, the newborn expired 13 h after birth.

Clinical discussion
Cyclopia leads to a stillbirth since the brain and other parts of the body do not grow normally in fetuses with this disorder. Moreover, it can be diagnosed using ultrasonography while the fetus is growing inside the uterus.

Conclusion
Early diagnosis during pregnancy using diagnostic methods and proper management of this abnormality should be emphasized to prevent further harm to the newborn and the mother with this syndrome. Moreover, many of these newborns should be offered early neonatal palliative care.

Full text

International Journal of Surgery Case Reports 88 (2021) 106548
Available online 4 November 2021
2210-2612/© 2021 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Case report
Cyclopia, a newborn with a single eye, a rare but lethal congenital anomaly:
A case report
Naser Parizad
a
, Navid Faraji
b
, Amireh Hassanpour
c
, Rasoul Goli
b
,
*
, Sajjad Rostami
d
,
Akram Amanollahzadeh
b
a
Patient Safety Research Center, Clinical Research Institute, Nursing & Midwifery School, Urmia University of Medical Sciences, Urmia, Iran
b
Department of Medical-Surgical Nursing, School of Nursing and Midwifery, Urmia University of Medical Sciences, Urmia, Iran
c
Department of Nursing, School of Nursing and Midwifery, Urmia University of Medical Sciences, Urmia, Iran
d
Department of Nursing, School of Nursing and Midwifery, Islamic Azad university of Zanjan, Zanjan, Iran
ARTICLE INFO
Keywords:
Cyclopia
Holoprosencephaly (HPE)
Neonate
Case report
ABSTRACT
Introduction and importance: Cyclopia is a rare congenital disorder characterized by facial abnormalities. In this
condition, the orbits of the eye are not properly divided into two cavities so that they can be seen either as a
single eye eld or two bilateral elds that are very close to each other. This syndrome affects the embryos that
are either aborted or stillborn upon delivery or, at best, die shortly after birth.
Case presentation: This case report is of a 37-week- and 5-day-old female fetus with a birth weight of 2300 g, a
height of 43 cm, and a head circumference of 31 cm. She was born to a 44-year-old mother through normal
vaginal delivery at Mahzad Hospital, Urmia, Iran. In the physical examination, an eye and a 4-cm proboscis were
seen in the middle of the forehead. The newborn also had no nose, and his outer ears were normal. No cleft lip or
cleft palate was observed. Unfortunately, the newborn expired 13 h after birth.
Clinical discussion: Cyclopia leads to a stillbirth since the brain and other parts of the body do not grow normally
in fetuses with this disorder. Moreover, it can be diagnosed using ultrasonography while the fetus is growing
inside the uterus.
Conclusion: Early diagnosis during pregnancy using diagnostic methods and proper management of this abnor-
mality should be emphasized to prevent further harm to the newborn and the mother with this syndrome.
Moreover, many of these newborns should be offered early neonatal palliative care.
1. Introduction
Cyclopia is a rare genetic disorder occurring as a birth defect [1]. Its
incidence rate is reported to be 1 in 13,000 to 20,000 newborns [2]. In
this health condition, the eye's orbits are not properly divided into two
cavities so that they can be seen either as a single eye eld or two
bilateral elds that are very close to each other [3]. This congenital
disorder affects both animals and humans [4]. Patients with cyclopia
syndrome typically have a missing or dysfunctional nose with a long
snout. The outer ears are usually curved, broken, or crumpled inwards.
Most patients also have a 3- to 5-cm polyp in the middle of the forebrain
[3]. This syndrome mostly affects the embryos that are either aborted or
stillborn upon delivery or, at best, die shortly after birth [5].
This study reports the clinical condition of a baby born with cyclopia
and who died after enduring this anomaly for 13 h. This case report was
reported according to the SCARE 2020 Guidelines to ensure the quality
of reporting [6].
2. Case presentation
The present case report is of a 37-week- and 5-day-old female fetus
born to a 44-year-old Kurdish mother through normal vaginal delivery
at Mahzad Obstetrics and Gynecology Hospital, Urmia, Iran. She (his
mother) had a history of cesarean delivery at the age of 32, where the
newborn was completely healthy. She was from a family with low so-
cioeconomic status and lives in a village far from Urmia city. She had
seen a gynecologist only once during this pregnancy and had not per-
formed any pregnancy examinations or diagnostic evaluations such as
ultrasonography. She also mentioned a history of taking levothyroxine
for her hypothyroidism. She had no history of smoking and denied a
* Corresponding author at: Nursing and Midwifery Faculty, Campus Nazlu, 11 KM Road Seru, Urmia, West Azerbaijan Postal Code: 575611-5111, Iran.
E-mail addresses: rasoulgoli94@gmail.com, Goli.r@umsu.ac.ir (R. Goli).
Contents lists available at ScienceDirect
International Journal of Surgery Case Reports
journal homepage: www.elsevier.com/locate/ijscr
https://doi.org/10.1016/j.ijscr.2021.106548
Received 1 October 2021; Received in revised form 19 October 2021; Accepted 27 October 2021

International Journal of Surgery Case Reports 88 (2021) 106548
2
history of alcohol and drug abuse. Moreover, she did not state any his-
tory of exposure to teratogens during pregnancy, especially in the rst
trimester. During history-taking at admission, the parents did not
mention the history of congenital anomalies or close family marriage in
their relatives.
After the onset of labor signs, the mother went to the hospital and
gave birth to a 37-week- and 5-day-old female fetus with a birth weight
of 2300 g, height of 43 cm, and head circumference of 31. In the initial
physical examination, an eye and a 4-cm proboscis were seen in the
middle of the forehead (Fig. 1). The newborn had no nose, and his outer
ears were normal. Although the newborn had micrognathia, no cleft lip
or cleft palate was observed [see Additional le]. The newborn's skin
was cyanotic, possibly due to hypoxia. His vital signs at birth were as
follows: Temperature: 36.3, Heart Rate: 183 bpm, Respiration Rate: 69
bpm, Blood Pressure: 57/25 mmHg, Oxygen Saturation: 86%. The
newborn's Apgar score could not be calculated. He was transferred to the
Neonatal Intensive Care Unit (NICU) and placed in an incubator. In the
chest X-ray conducted at birth, the newborn's right lung was shown to be
completely collapsed (Fig. 2). Therefore, to manage this condition, a
chest tube was immediately placed in the right chest. We used the
ventilator for the newborn continuously until the newborn died.
Cyclopia may sometimes also be associated with cardiac defects (e.g.,
atrial septal defect, hypoplastic left heart, anomalous communication
between right ventricle and aorta). However, in this case, the echocar-
diography report did not show any associated cardiac abnormalities.
Moreover, brain MRI demonstrated the fusion of the frontal horns of the
lateral ventricles with abnormal genu and rostrum of the corpus cal-
losum and partial fusion of the cingulate gyrus anteriorly. The anterior
cerebral artery was azygous and displaced anteriorly. This newborn had
features consistent with lobar holoprosencephaly (Fig. 3), including a
poorly formed corpus callosum and azygous anterior cerebral artery.
Other organs were shown to be normal, and no other congenital mal-
formations were found. Unfortunately, the newborn expired within 13 h
after birth. Unfortunately, her parents did not give consent for an
autopsy.
3. Discussion
Holoprosencephaly is a common brain defect that often leads to
facial anomalies such as close ocular orbits, microcephaly, cleft lip, and
cleft palate. Holoprosencephaly is a disorder caused by the failure of the
prosencephalon (fetal forebrain) to adequately develop and divide into
the left and right hemispheres [7]. This disorder results in the formation
of a single-lobed brain structure and severe craniofacial defects. In most
cases of holoprosencephaly, the abnormalities are so severe that neo-
nates die before birth [8]. Holoprosencephaly consists of three subtypes,
including alobar, semi-lobar, and lobar holoprosencephaly. In the alobar
subtype, the brain is not divided, and there are severe facial defects. In
the semi-lobar subtype, the brain's hemispheres are partially divided and
cause a moderate form of the disorder. There are two separated hemi-
spheres in the lobar subtype with minor structural defects [8,9].
In patients with milder forms of holoprosencephaly, craniofacial
defects include microcephaly, orbital hypotelorism, at nasal bridge,
and abnormal anterior teeth. In this regard, the cleft lip is the mildest
facial abnormality in holoprosencephaly [9], while the most severe
facial abnormality is cyclopia. In patients with cyclopia, a hereditary
disease, the face is seen with a single eye eld and an incomplete nose
above the eye [2]. Parents of neonates with cyclopia should warn their
Fig. 1. The newborn with cyclopia syndrome.
Fig. 2. The chest radiograph of the newborn with cyclopia.
N. Parizad et al.

International Journal of Surgery Case Reports 88 (2021) 106548
3
rst-degree relatives who may be forming a family about the increased
risk of cyclopia or other milder forms of holoprosencephaly [10].
The present case report is of a 37-week- and 5-day-old female fetus
born to a 44-year-old mother. The newborn had no nose, and no cleft lip
or cleft palate was observed, although the newborn had micrognathia.
The newborn's skin was cyanotic. Chest X-ray revealed that the new-
born's right lung was completely collapsed. Therefore, to manage this
condition, a chest tube was immediately placed. We ventilated the
newborn continuously until she died. Brain MRI demonstrated that the
newborn had the characteristics of lobar holoprosencephaly, including a
poorly formed corpus callosum and azygous anterior cerebral artery.
As there is no cure for this condition, legal abortion is the solution to
prevent further harm to the newborn and the mother. Recognizing po-
tential risk factors and informing parents is another suggested solution.
Ingestion of certain plants during pregnancy can increase the risk of
cycops and should be avoided.
The Sonic Hedgehog (SHH) gene is located in the long arm of chro-
mosome 7 (7q35.1 band) and regulates the expression and synthesis of
proteins in the nervous system to form the correct shape of the brain.
SHH gene also regulates the correct formation of the hands and nose.
Furthermore, the Paired Box 6 (PAX6) gene regulates the correct syn-
thesis and development of the eyes. In cyclopia, the above genes mutate
and lose their normal function. The SHH gene plays a key role in pro-
moting the expression of other genes in the cell, such as PAX6 and PAX2
[11].
Cyclopia can be diagnosed using ultrasonography while the fetus is
growing inside the uterus. This congenital disorder occurs between the
third and fourth weeks of pregnancy, and conducting medical ultra-
sound after this time can usually show obvious signs of cyclopia or other
forms of holoprosencephaly. In addition to orbital hypotelorism,
abnormal formation of the fetus's brain and internal organs may be seen
on ultrasound [12]. When the ultrasound shows an abnormality but
cannot provide a clear picture, the physician may recommend fetal
Magnetic Resonance Imaging (MRI). If cyclopia is not diagnosed during
the pregnancy, it can be diagnosed by medically examining the newborn
at birth [3].
The exact causes of cyclopia remain unknown [4]. However, re-
searchers believe that several factors can increase the risk of cyclopia.
These include genetic factors, multiple pregnancies, especially twinning,
female sex, previous unexplained miscarriages, gestational diabetes,
infections during pregnancy, exposure to UV light, smoking, using
alcohol and certain medications during pregnancy, and cyclopamine - a
highly alkaloid toxin. Another risk factor related to this anomaly is
Veratrum californicum, found in corn lily or false hellebore. It is impli-
cated in causing cyclopia (when ingested believing the plant to be hel-
lebore, which can cure the morning sickness symptoms associated with
the rst few months of pregnancy) [4,5].
Cyclopia often leads to a stillbirth since the brain and other parts of
the body do not grow normally in fetuses with this disorder. The brain of
a neonate with cyclopia cannot manage the formation of the other or-
gans that are necessary for survival [13]. In 2015, the live birth of a
newborn with cyclopia was reported in Jordan. The newborn died in
hospital within 5 h after birth [14]. Most studies have shown that a baby
born with cyclopia syndrome has a maximum lifespan of 10–12 h
[1,3,13], but despite the anomaly of the respiratory system, our case
survived 13 h, which was the longest survival time of a newborn with
cyclopia syndrome. A newborn who develops cyclopia often does not
survive pregnancy. This is because the brain and other organs do not
develop normally. The brain of a newborn with cyclopia cannot sustain
all the body's systems needed to survive.
Newborns with this lethal congenital malformation, even if they
survive longer than expected, become severely impaired and palliative
care should be considered. The goals of palliative care in the neonatal
context are to prevent and relieve pain and suffering of neonates and
provide support for families. Such care includes planning with the
family about the practicalities of the death and continuing family sup-
port after the baby dies [15]. Prenatal palliative care emphasizes the
importance of planning for the experience of losing an infant. Pre-natal
diagnosis of congenital heart defects produces an ethical dilemma for
both parents and physician. The right to decide should be left to the
parents, while the caregivers have to support them with nondirective
counselling, with the information necessary for parental decision [16].
4. Conclusion
Early diagnosis of cyclopia during pregnancy using diagnostic
methods such as ultrasonography and the proper management of this
abnormality should be strongly emphasized to prevent further harm to
the newborn and the mother. However, such cases remain undiagnosed
in developing countries where pregnant women do not receive regular
prenatal care.
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.ijscr.2021.106548.
Sources of funding
None.
Ethical approval
All ethical principles were considered in conducting this case report.
All patient information kept condential.
Consent
Written informed consent was obtained from the patient for publi-
cation of this case report and accompanying images. A copy of the
written consent is available for review by the Editor-in-Chief of this
journal on request.
Authors' contributions
NP, AH, AA, NF, SR, and RG contributed in data collection, manu-
script drafting and reviewing, and approval of nal manuscript. RG and
NP has contributed in case management, data collection, manuscript
Fig. 3. Infant's brain MRI with lobar holoprosencephaly features.
N. Parizad et al.

International Journal of Surgery Case Reports 88 (2021) 106548
4
drafting and reviewing, and approval of nal manuscript. NP performed
the study supervision.
Research registration
Not applicable.
Guarantor
Rasoul Goli.
Provenance and peer review
Not commissioned, externally peer-reviewed.
Declaration of competing interest
None.
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