Alobar Holoprosencephaly With Cyclopia: A Rare Lethal Anomaly

Abstract

Cyclopia is the most severe form of alobar holoprosencephaly and is a rare congenital craniofacial abnormality. Cyclopia is characterized by the fusion of the orbits, absence of the nose, and presence of a proboscis. Cyclopia has an unknown and varied etiology, with both genetic and environmental factors playing a role. A 27-year-old female (G 4 P 3 L 3) presented with obstructed labor. With the assistance from medical personnel, she delivered a live female neonate through cesarean section. The neonate was born with multiple defects, which was diagnosed as a rare case of holoprosencephaly with cyclopia. The neonate had a single central slitlike orbital groove, a single eye, a superiorly attached blind-ending proboscis, no nose, and a well-formed mouth. However, the neonate died soon after birth.

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PER INATOLOGY • Vol 22 • No. 3• Supplement 1 • S13 5
Alobar Holoprosencephaly
With Cyclopia: A Rare Lethal
Anomaly
Soniya Vishwakarma, Ramesh Chand*
*Correspondence
Dr Ramesh Chand
Assistant Professor
Flat No. 202, G Block
Type 3, New Campus
Uttar Pradesh University of
Medical Sciences, Saifai
Etawah 206130, Uttar Pradesh
India
E-mail: maildrramesh@gmail.com
Abstract
Cyclopia is the most severe form of alobar holoprosencephaly
and is a rare congenital craniofacial abnormality. Cyclopia is
character ized by the fusion of the orbits, absence of the nose,
and presence of a proboscis. Cyclopia has an unknown and
varied etiology, with both genetic and environmental factors
playing a role.
A 27-year-old female (G4P3L3) presented with obstructed labor.
With the assistance from medical personnel, she delivered a
live female neonate through cesarean section. The neonate
was born with multiple defects, which was diagnosed as a rare
case of holoprosencephaly with cyclopia. The neonate had a
single central slitlike orbital groove, a single eye, a superiorly
attached blind- ending proboscis, no nose, and a well-formed
mouth. However, the neonate died soon after birth.
Key Words: Holoprosencephaly, cyclopia, micrognathia,
proboscis, single eye, facio-cerebral developmental deformity
Case Report
Introduction
e term “cyclopia” is derived from the word
“cyclops”, which means the single-eyed giants of
Greek mythology. Cyclopia is the most severe form of
holoprosencephaly and a serious median facio-cere-
bral developmental deformity. A fetus with cyclopia
can either be stillborn or die soon after birth.1 One in
16,000 live births and 1 in 250 embryos are aected by

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Vishwakarma S, et al. Alobar Holoprosencephaly With Cyclopia
holoprosencephaly.2 Further, 1.05 of 100,000 (includ-
ing stillbirths) neonates are aected with cyclopia.3
Cyclopia is characterized by a median single eye or a
partially divided eye inside a single orbit, no nose, and a
proboscis above the eye.
In this case report, we discuss this rare congenital con-
dition to create awareness about regular antenatal visits
and scans for early detection of fetal anomalies.
Case Description
A 27-year-old woman (G4P3L3) visited the Uttar
Pradesh University of Medical Sciences (Etawah, Uttar
Pradesh, India) and had an obstructed labor. She had
a history of 3 normal vaginal deliveries, and all the 3
children were alive. She was nondiabetic, nonhyperten-
sive, and had no history of consanguinity, smoking, or
alcohol intake. Also, there was no history of any infec-
tions or medication during pregnancy. She was mildly
anemic (Hb, 9.1 g%), whereas her other laboratory
investigations were normal, including blood glucose
level. Her abdominal examination showed a term-size
uterus. e fetus was observed to be in longitudinal lie
position with a vertex presentation, and the fetal head
was 3/5 palpable above the pelvic brim with fetal brady-
cardia. Pelvic examination showed vulval edema, fully
dilated cervix, and hot and dry vagina with a clear pic-
ture of obstructed labor. Hence, she was considered
for an emergency cesarean section after initial uid
management.
She delivered a female neonate weighing 3.6 kg with
congenital anomalies. e neonate died shortly after
birth. e gross examination showed only one eye in
the middle of the forehead (cyclopia), no nasal opening,
and proboscis in the midline. e neonate’s ears were
normal, the hair was dense and low implanted, and
there was no cleft lip or cleft palate, but micrognathia
was observed. e neonate’s other organs, including
the umbilical cord and the spine, were normal, and
no other congenital anomalies were noticed. e par-
ents refused a postmortem examination of the neonate
because of religious beliefs. e father of the neonate
consented for reporting the case in a medical journal
(Figures 1 and 2).
Discussion
Cyclopia is characterized by medial monophthal-
mia, arhinia, proboscis, and sometimes short eyelids
with or without eyelashes.4 In some cases, the sclerous
tissue separates the single optic nerve into 2 contigu-
ous optic nerves. Usually, the hair is dense and low
implanted. In case of associated otocephaly, the ears
can be normal or curved and atrophied or contiguous
on the midline.
Cyclopia is the most severe form of facial deformity
that can occur because of alobar holoprosencephaly (a
complicated human brain abnormality). Between the
18th and 28th day of pregnancy, the prosencephalon of
the embryo fails to divide into the right and left hem-
ispheres, resulting in holoprosencephaly. ere are 2
types of holoprosencephaly: the classic interhemispheric
variant and the middle interhemispheric variant.
Case Report
Figure 1. The Newborn With Cyclopia
Figure 2. Cyclopia Deformity (A Single Orbit in the
Midline With No Nasal Aperture)

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Vishwakarma S, et al. Alobar Holoprosencephaly With Cyclopia
a total of 14 gene mutations have been identied, the
SHH gene mutation is the most common cause of
holoprosencephaly.7 Furthermore, 40% of holoprosen-
cephaly cases are associated with numerical chromo-
somal defects, the most common of which is trisomy 13.
Diagnosis
Holoprosencephaly can be diagnosed with the help of a
2-dimensional obstetric ultrasonography (USG), a high-
resolution 4-dimensional scan, or a fetal magnetic res-
onance imaging (MRI). In addition, a fetal MRI also
helps in detecting other associated craniofacial anoma-
lies and diagnosing lobar, semilobar, and lobar varieties.
e presence of fused thalami and fused cerebral cortex
in alobar holoprosencephaly distinguishes it from hydra-
nencephaly on fetal MRI.9 Other diagnostic modalities
that help diagnose holoprosencephaly are cytogenetic
analysis and molecular analysis of the fetal DNA.
Management
After holoprosencephaly is conrmed, it is advis-
able to terminate the pregnancy after a level-2 USG.
Holoprosencephaly, both alobar and semilobar, is fatal.
Neonates born with lobar holoprosencephaly can survive
for some years. ose born with mild lobar type require
lifelong complex treatment, including hormone replace-
ment therapy, correction of electrolyte and acid–base
imbalances, permanent gastrostomy tube, and surgical
repair of facial anomalies. ere is also a 6% risk of recur-
rence of holoprosencephaly in cases with sporadic origin.10
Conclusion
Cyclopia is a very rare craniofacial malformation often
incompatible with life. e most striking feature is the
central diamond-shaped palpebral ssure containing
a single eye associated with a nasal proboscis. During
the antenatal period, a level-2 USG can easily pick this
anomaly, after which the pregnancy can be terminated.
However, such cases go undiagnosed in impoverished
countries as women do not receive appropriate regular
antenatal care and a prenatal diagnosis. Hence, we wish
to create awareness about such conditions and encour-
age regular antenatal visits and scans.
Classic interhemispheric variant
e classic interhemispheric variant of holoprosenceph-
aly is a complex human brain malformation that results
from incomplete cleavage of the prosencephalon into
right and left hemispheres, occurring between the 18th
and the 28th day of gestation. Based on the severity,
it is further classied into alobar, semilobar, and lobar
subtypes, with alobar being the most severe form.5
Alobar holoprosencephaly: In this condition, the
prosencephalon fails to cleave sagittally into the cere-
bral hemispheres, transversely into the telencephalon
and diencephalon, and horizontally into the olfactory
tracts and bulbs. In cyclopia, 3 forms of eye deformities
can be observed: monophthalmia in which only 1 eye is
formed, synophthalmia in which 2 eyeballs are fused,
and anophthalmia in which eyeballs are absent.
Semilobar holoprosencephaly: In this condition, the
primary posterior interhemispheric ssures in rudimen-
tary cerebral lobes are incomplete. Usually, in this con-
dition, the olfactory tracts and bulbs do not develop.
Lobar holoprosencephaly: In this condition, the brain
is mostly well-formed, with normal-sized cerebral hemi-
spheres. But the corpus callosum may be missing or hypo-
plastic or normal, while the olfactory tracts and bulbs
may be absent or hypoplastic.
Middle interhemispheric variant
e middle interhemispheric variant or syntelencephaly
is a milder form of holoprosencephaly. It is characterized
by the absence or incomplete formation of the dorsal
forebrain midline that mostly aects the posterior fron-
tal and parietal lobes.6
Causative factors
Holoprosencephaly is an autosomal dominant disor-
der that can be passed down through generations.7
Holoprosencephaly is caused by a combination of heredi-
tary and environmental factors. Maternal diabetes melli-
tus, smoking, consumption of alcohol, in utero infections
(eg, cytomegalovirus, rubella, or toxoplasmosis), and sev-
eral medicines (eg, antiepileptics, methotrexate, and mis-
oprostol) are a few environmental factors.8 Although
Case Report

S138 • PE RINATOLOGY • Vol 22 • No. 3 • Supplement 1
Vishwakarma S, et al. Alobar Holoprosencephaly With Cyclopia
Acknowledgment
We express our gratitude toward the parents of the neo-
nate for consenting to publish this case report.
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Authors’ Affiliations
Dr Soniya Vishwakarma, Assistant Professor, Department of Obstetrics and Gynecology; Dr Ramesh Chand, Assistant Professor,
Department of Pediatrics, Uttar Pradesh University of Medical Sciences, Saifai, Etawah 206130, Uttar Pradesh, India
Case Report