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Semilobar Holoprosencephaly with Congenital
Oropharyngeal Stenosis in a Term Neonate
Kenji Hishikawa, MD1Hideshi Fujinaga, MD1Chie Nagata, MD, PhD, MPH2Masataka Higuchi, MD3
Yushi Ito, MD1
1Division of Neonatology, National Center for Child Health and
Development, Tokyo, Japan
2Division of Education for Clinical Research, National Center for Child
Health and Development, Tokyo, Japan
3Division of Pulmonology, Department of Medical Subspecialties,
National Center for Child Health and Development, Tokyo, Japan
Am J Perinatol Rep 2015;5:e109–e110.
Address for correspondence Kenji Hishikawa, MD, Division of
Neonatology, Center of Maternal-Fetal, Neonatal and Reproductive
Medicine, National Center for Child Health and Development, 2-10-1
Okura Setagaya-ku, Tokyo 157-8535, Japan
(e-mail: hishikawa.k1234@gmail.com).
Holoprosencephaly (HPE) is a common developmental disorder
that occurs in the human forebrain. The cause of HPE is thought
to be because of a disturbance in the delicate balance of signals
for the separation of the cerebral hemisphere.1HPE is classified
into the following four types according to the severity of the
abnormality of cleavage of the cerebral hemispheres and deep
nuclear structures: alobar, semilobar, lobar, and middle inter-
hemispheric variant or syntelencephaly.2Although HPE is often
accompanied by a deficit in midline facial development, there
has been no report on HPE with congenital oropharyngeal
stenosis. Here, we report a case of HPE with congenital oropha-
ryngeal stenosis, which resulted in respiratory distress.
Case Presentation
A 33-year-old pregnant woman (Gravida 1, Para 0) was
referred to our hospital for fetal growth retardation and fetal
ventriculomegaly at 30 weeks of gestation. She had no history
of infections during pregnancy, medication, or any other
chronic diseases. Her niece had a congenital abnormality,
but the details were unclear. Prenatal sonographic findings
revealed fetal growth retardation (2.0 standard deviation
[SD]), enlargement of the anterior and posterior horns of the
bilateral lateral ventricles, fused lateral ventricles and thala-
mi, and hypotelorism (binocular distance, 37.8 mm, <2.0
SD). No other congenital malformations were found. Prenatal
diagnosis was semilobar HPE. Amniocentesis was performed
and the chromosomal karyotype was normal (46,XX). The
course of pregnancy was uneventful. At 39 weeks of gestation,
she had spontaneous labor and vaginal delivery.
A female baby of weight 2,172 g (2.2 SD) was born. The
Apgar scores at 1 and 5 minutes were 7 and 9 points, respective-
ly. Her respiratory status was stable at birth and hence resusci-
tation was not required. She was transferred to the neonatal
intensive care unit (NICU) for further examination.
In the NICU, the newborn’s vital signs were within normal
limits. Physical examinations showed microcephaly (head cir-
cumference, 29.7 cm; 2.6SD),hypotelorism(magnetic
Keywords
►holoprosencephaly
►oropharyngeal
stenosis
►congenital
pharyngeal stenosis
Abstract Background Holoprosencephaly (HPE) is often accompanied by a deficit in midline
facial development; however, congenital oropharyngeal stenosis in neonates with HPE
has not been reported before. We describe a case of a neonate with prenatally
diagnosed semilobar HPE accompanied by congenital oropharyngeal stenosis.
Case Report Thepatientwasbornat39weeksofgestationanddevelopeddyspnea
shortly after. Laryngoscopic test revealed oropharyngeal stenosis. Nasal continuous
positive airway pressure, high-flow nasal cannula, and nasopharyngeal airway did not
resolve her dyspnea; tracheostomy was required.
Conclusion Neonates with HPE might be at higher risk of pharyngeal stenosis because
of the functional and/or anatomical abnormalities. In the case of dyspnea in neonates
with HPE, laryngoscopic evaluation should be considered.
received
November 5, 2014
accepted after revision
February 12, 2015
published online
April 6, 2015
DOI http://dx.doi.org/
10.1055/s-0035-1548725.
ISSN 2157-7005.
Copyright © 2015 by Thieme Medical
Publishers, Inc., 333 Seventh Avenue,
New York, NY 10001, USA.
Tel: +1(212) 584-4662.
THIEME
Case Report e109
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resonance imaging [MRI] findings at 2 months: interocular
distance, 10.1 mm, <2.0 SD; binocular distance, 47.3 mm, <
2.0SD) and hypoplasia of nasal septum. Cleft lip, cleft palate,
microstomia, and micrognathia were not found. Neurologically,
she had normal tone and reflexes. Brain sonography and MRI
findings were in line with her prenatal examinations. There
were no abnormal findings in her blood tests, chest and
abdominal X-rays, echocardiography, and abdominal sonogra-
phy. We diagnosed semilobar HPE, which was consistent with
her prenatal diagnosis.
On day 1 of life, the newborn developed dyspnea with stridor.
Her breathing worsened gradually accompanied by retraction and
hypercapnia; nasal continuous positive airway pressure (nCPAP)
was initiated on day 4. On day 7, we performed a laryngoscopic
evaluation of her upper airway. Her oropharyngeal lumen was
narrow, plugged by secretion and opened slightly with labor only
during inspiration (►Fig. 1). A diagnosis of oropharyngeal steno-
sis was made. We deemed the patient too small in size for
nasopharyngeal airway (NPA) insertion. Her respiratory status
was initially stabilized but deteriorated progressively, with nCPAP
or high-flow nasal cannula rendered ineffective. We placed an
NPA through the oropharyngeal stenotic portion on day 35, which
resulted in the resolution of her dyspnea. However, an erosion of
the wall of her oropharynx just above the larynx developed soon
after because of the continuous use of the NPA, leading to
difficulties in inserting an NPA consecutively. Furthermore, the
NPA was easily obstructed by respiratory secretion. Frequent
suction and washing of the NPA was required, rendering her
breathing unstable. Wesuccessfully performed a tracheostomy on
day 112 when her weight was 4,468 g. Consequently, her
breathing became easy and stable.
Discussion
Toourknowledge,thisisthefirst report of HPE with congenital
oropharyngeal stenosis, which is a very rare condition. Previ-
ously, Kawashiro et al reported on congenital pharyngeal steno-
sis.3The authors categorized anatomical stenosis into the
following three types: type 1 was associated with mandibular
hypoplasia (e.g., Pierre Robin syndrome); type 2 was associated
with mandibulofacial dysostosis (e.g., Apert syndrome and
Crouzon syndrome); and type 3 was associated with structural
abnormalities (e.g., abnormal proliferation of pharyngeal wall
tissues). To date, no firm conclusions about the pathogenesis
congenital pharyngeal stenosis have been drawn because of the
scarcity of reports on this condition. However, we postulate that
congenital pharyngeal stenosis could be because of the various
causes including abnormal neuromuscular factors and anatomi-
cal stenosis. In this case, laryngoscopic evaluation of upper
airway revealed a narrowing of the oropharyngeal lumen which
opened slightly only during inspiration. We did not find other
common etiologies of dyspnea such as respiratory distress
syndrome, transient tachypnea of the newborn, pulmonary air
leak, rhinostenosis, choanal stenosis, and laryngomalacia. In
addition, we did not observe any mass lesion that was pressing
on her oropharynx. Two possible etiologies/mechanisms that
could have resulted in the patient’s oropharyngeal stenosis are
functional pharyngeal stenosis caused by neurogenic factors
associated with HPE, and anatomical pharyngeal stenosis caused
by mandibulofacial dysostosis with hypotelorism and hypoplasia
of nasal septum. Neonates with HPE might be at higher risk of
pharyngeal stenosis because of functional and/or anatomical
abnormalities. In the case of dyspnea with HPE, pharyngeal
stenosis may not be evaluated sufficiently.
The effect of nCPAP, HFNC, and NPA on our patient was
temporary. The air pressure of nCPAP and HFNC seemed to be
insufficient to open the patient’s oropharynx. For the NPA, the
tip was needed to be placed in the small space between the
narrow segment of the patient’s oropharynx and the epiglottis.
It was challenging to keep the NPA at the suitable position
because of movements of the patient. As a result, erosion
occurred in the wall of her oropharynx. Although Kawashiro
et al recommended uvula splitting as an alternative treatment,
we were unable to use this option because the newborn’s
physique was too small to tolerate such a procedure. Instead, a
tracheostomy was performed to resolve her problem.
In summary, we experienced a case of HPE with congenital
oropharyngeal stenosis which resulted in respiratory distress.
In the case of dyspnea with HPE, laryngoscopic test should be
considered for the evaluation of pharyngeal stenosis.
Conflict of Interest
The authors declare no conflict of interest.
Acknowledgment
We thank Dr. Julian Tang of the Department of Education
for Clinical Research, National Center for Child Health and
Development, for proofreading and editing this article.
References
1Kauvar EF, Muenke M. Holoprosencephaly: recommendations for
diagnosis and management.Curr Opin Pediatr 2010;22(6):687–695
2Dubourg C, Bendavid C, Pasquier L, Henry C, Odent S, David V.
Holoprosencephaly. Orphanet J Rare Dis 2007;2:8
3Kawashiro N, Koga K, Tsuchihashi N, Araki A. Choanal atresia and
congenital pharyngeal stenosis. Acta Otolaryngol Suppl 1994;
517:27–32
Fig. 1 Laryngoscopic findings of the oropharynx. We looked down the
patient’s oropharynx from the posterior nasal cavity. Her oropharyn-
geal lumen was narrow, plugged by secretion, and opened slightly with
labor only during inspiration.
American Journal of Perinatology Report s Vol. 5 No. 2/2015
Holoprosencephaly with Oropharyngeal Stenosis Hishikawa et al.e110
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