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Case Report
Antenatally Diagnosed Alobar Holoprosencephaly: A Report of Two Cases Abstract
Holoprosencephaly is a complex developmental abnormality of the brain arising from the failure of cleavage of the prosencephalon. The condition termed “holoprosencephaly” includes cyclopia, cebocephaly, ethmocephaly, and median cleft. We present two cases of antenatally diagnosed alobar holoprosencephaly with multiple associations, which were confirmed after termination of pregnancy. One of them had a proboscis and a single midline eye. The other had multiple facial abnormalities such as hypotelorism, median cleft lip and palate, and preauricular skin tag. Keywords: Cyclopia, holoprosencephaly, proboscis, ultrasound
Introduction Holoprosencephaly is a disorder caused by the absence or incomplete diverticulation and cleavage of the prosencephalon into the cerebral hemispheres and lateral ventricles. The incidence of holoprosencephaly is 1:250 during embryogenesis and 1:16,000 of all the births.[1] Cyclopia has been reported to occur in 1:40,000 births and median cleft has been reported to occur at a rate of 1:16,000 births.[2] Females are affected three times more than the males with a female:male ratio of 3:1.[3]
Case Report A 22‑year‑old primigravida with 7 months of amenorrhea presented to the radiology department for obstetric ultrasonography (USG) examination as a part of the routine antenatal checkup. There was no history of consanguinity. USG revealed single live intrauterine fetus corresponding to gestational age of 28 weeks 4 days. Bilateral lateral ventricles were enlarged and fused with centrally fused thalami and peripherally compressed cerebral parenchyma [Figure 1]. The falx cerebri, septum pellucidum, and corpus callosum were completely absent. The facial features were dysmorphic with centrally fused orbits forming single eye called the cyclops, and an external midline soft tissue projection was seen the proboscis [Figure 2]. The nose was not seen separately. The findings were better appreciated on three‑dimensional This is an open access article distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as the author is credited and the new creations are licensed under the identical terms. For reprints contact:
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C. R. Srinivasa Babu, Inampudi Vineel, Arjun Prakash, Y. Ravi Kumar Department of Radio‑diagnosis, PES Institute of Medical Sciences and Research, Kuppam, Andhra Pradesh, India
images [Figure 2a]. The pregnancy was terminated, and antenatal findings were confirmed postnatally [Figure 2b]. Another 21‑year‑old gravida two, para one female with 6 months of amenorrhea presented to the department for a routine antenatal USG scan. Medical and family histories were unremarkable, with the previous child being born at term with no congenital anomaly. Her general physical examination was normal. A routine antenatal USG revealed a central large monoventricle with surrounding thin mantle of cerebral parenchyma [Figure 3]. The septum pellucidum, falx cerebri, and interhemispheric fissure were absent. Both the thalami were fused [Figure 3]. There was associated hypotelorism [Figure 4a and b], median cleft lip [Figure 4a and c], depressed nasal bridge, left preauricular skin tag [Figure 4a], and gastroschisis with a portion of liver protruding out through the defect in the anterior abdominal wall [Figure 5]. Rest of the fetus was normal. The antenatal USG features were confirmed postpartum [Figure 5b].
Discussion Holoprosencephaly is a complex developmental abnormality of the brain arising from failure of cleavage of prosencephalon. Prosencephalon is the most rostral of the three primitive cerebral vesicles and gives rise to cerebral hemispheres and diencephalic structures (including neurohypophysis, thalami, third
Address for correspondence: Dr. Inampudi Vineel, S/o I. Ramesh Babu, H/N 8‑114, Nidamanuru, Vijayawada Rural, Krishna District ‑ 522 104, Andhra Pradesh, India. E‑mail: vineel.inampudi@gmail. com
Access this article online Website: www.cjhr.org DOI: 10.4103/cjhr.cjhr_23_17 Quick Response Code:
How to cite this article: Srinivasa Babu CR, Vineel I, Prakash A, Kumar YR. Antenatally diagnosed alobar holoprosencephaly: A report of two cases. CHRISMED J Health Res 2017;4:283-5.
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Figure 1: (a and b) Antenatal ultrasonography shows central large monoventricle with surrounding thin mantle of cerebral parenchyma and fused thalami. The falx cerebri, septum pellucidum, and corpus callosum are absent. An external midline soft tissue projection is seen‑proboscis (green arrow)
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Figure 2: (a) Three‑dimensional ultrasonography image clearly delineates the proboscis (green arrow) with extreme degree of hypotelorism leading to cyclops (red arrow). (b) Postnatal image confirms the presence of proboscis (green arrow) and cyclops (red arrow)
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Figure 3: Antenatal ultrasonography axial section shows central large monoventricle with surrounding thin mantle of cerebral parenchyma with fused thalami. The septum pellucidum, falx cerebri, and interhemispheric fissure are absent
ventricle, and optic bulbs). This differentiation process is thought to be induced by prechordal mesenchyme interposed between roof of the mouth and prosencephalon. The same tissue is responsible for normal development of median facial structures (forehead, nose, interorbital structures, and upper lip).[2] so any interference with the activity of prechordal mesenchyme would lead to defects in brain and face. The most relevant classification of holoprosencephaly for antenatal diagnosis is that suggested by Demyer, which recognizes three types: alobar, semilobar, and lobar according to the degree of incomplete division of prosencephalic derivatives.[2] According to the degree of failure of rotation, alobar holoprosencephaly is commonly subdivided into three types: pancake, cup, and ball varieties.[2] The association between facial anomalies and holoprosencephaly has led to the well‑known phrase, “the face predicts the brain.”[4] The most severe of facial malformations associated with alobar holoprosencephaly are cyclopia, ethmocephaly, and cebocephaly. The others are hypotelorism, median cleft lip and palate, lateral cleft lip and palate and pyriform aperture stenosis. Semilobar and lobar types show milder facial anomalies. However, similar faces are occasionally seen in the absence of 284
c Figure 4: (a and b) Antenatal ultrasonography shows extreme degree of hypotelorism, median cleft lip and left preauricular skin tag (red arrow). (c) Three‑dimensional image better depicts the hypotelorism, median cleft lip, and depressed nasal bridge
holoprosencephaly and presence of these facial features is not always diagnostic. Cyclopia is the most severe abnormality among the median cerebrofacial anomalies and mild hypotelorism with flat face being the least severe. Holoprosencephaly is often associated with chromosomal abnormalities, primarily trisomy 13, trisomy 18, and trisomy 13/15.[2] Alobar type shows no cleavage of prosencephalon with a large monoventricle surrounded by thinned out mantle with absent interhemispheric fissure, falx cerebri, corpus callosum, fornix, optic tract, neurohypophysis, and olfactory bulbs. The thalami are fused with absent third ventricle.[5] Failure of inward rotation of primitive cerebral hemispheres prevents the thin membranous roof of the ventricular cavity from being enfolded within the brain. Because of increase in cerebrospinal fluid, the membrane may balloon out to form a cyst between cerebral convexity and calvarium (so‑called dorsal cyst). There may be a complete absence of gyri with few shallow sulci. The single ventricle that persists shows a typical horseshoe
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help predict chromosomal anomalies and subsequent fetal outcome. Because of recent advances in development and improvement of high‑resolution USG, early diagnosis of congenital anomalies such as holoprosencephaly is now possible. Declaration of patient consent
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Figure 5: (a) Axial section at the level of abdomen shows gastroschisis with portion of liver protruding out through defect in anterior abdominal wall. (b) Postnatal images confirm presence of hypotelorism, median cleft lip (green arrow), depressed nasal bridge, and gastroschisis (red arrow)
shape when seen in coronal section. On the contrary, the posterior fossa contents which include cerebellum and brain stem are normal. Ultrasound is most helpful in prenatal diagnosis of holoprosencephaly especially of alobar type and is the decisive modality for the management and follow‑up of such cases so that the mother can opt for termination of pregnancy and doctor can decide for a vaginal delivery rather than caesarean section. It has already been emphasized previously about the association of hypotelorism and absent Falx for diagnosing holoprosencephaly.[6] Infants with alobar form usually die within 1st year of life.[2] When the diagnosis of alobar or semilobar holoprosencephaly is made before viability, the option of pregnancy termination with fetal karyotyping is indicated. When detected before 24 menstrual weeks, most women will elect to terminate pregnancy; when identified after 24 weeks, cephalocentesis may be a justifiable option.[7]
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Acknowledgment I, sincerely thank all my staff and co‑residents for their cooperation during the workup of this case report. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
References 1. 2.
3.
The decision‑making in lobar holoprosencephaly is difficult because data concerning outcome are not available.
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Conclusion
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Holoprosencephaly is a major malformation of the central nervous system that should be distinguished from other causes of fetal hydrocephalus. Awareness of the spectrum of sonographic findings seen with holoprosencephaly should improve the accuracy of prenatal diagnosis. Identification of concurrent facial and extracranial malformations can
6. 7.
Aruna E, Chakravarthy VK, Rao DN, Rao DR. Holoprosencephaly with multiple anomalies of the craniofacial bones‑an autopsy report. J Clin Diagn Res 2013;7:1722‑4. Romero R, Pilu G, Jeanty P, Ghidini A, Hobbins JC. The central nervous system. In: Delauter DL, editor. Prenatal Diagnosis of Congenital Anomalies. 1st ed. United States of America: Appleton and Lange A Publishing Division of Prentice Hall; 1988. p. 59‑65. Maduforo CO, Nwankwo NC, Etawo US, Ugwa RO. Holoprosencephaly in 11‑month old Nigerian male and review of literature. West Afr J Radiol 2011;18:63‑7. Demyer W, Zeman W, Palmer CG. The face predicts the brain: Diagnostic significance of median facial anomalies for holoprosencephaly (arhinencephaly). Pediatrics 1964;34:256‑63. Osborn AG. Holoprosencephalies, related disorders, and mimics. In: Renlund AR, editor. Osborn’s Brain: Imaging, Pathology and Anatomy. 1st ed. Canada: Amirsys Publishing, Inc.; 2013. p. 1115‑30. Agarwal R. Prenatal diagnosis of holoprosencephaly: Pictorial essay. Indian J Radiol Imaging 2000;10:93‑8. Nyberg DA, Mack LA, Bronstein A, Hirsch J, Pagon RA. Holoprosencephaly: Prenatal sonographic diagnosis. AJR Am J Roentgenol 1987;149:1051‑8.
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