Hallermann-Streiff syndrome with severe bilateral enophthalmos and radiological evidence of silent brain syndrome: a new congenital silent brain syndrome?

Abstract

We present the first case of a congenital form of silent brain syndrome (SBS) in a young patient affected by Hallermann-Streiff syndrome (HSS) and the surgical management of the associated eyelid anomalies.
HSS signs were evaluated according to the Francois criteria. Orbital computed tomography (CT) and genetic analysis were performed. An upper eyelid retractor-free recession was performed. Follow-up visits were performed at day 1, weeks 1 and 3, and months 3, 6, 9 (for both eyes), and 12 (for left eye) after surgery.
The patient exhibited six of the seven signs of HSS. Orbital CT showed bilateral enophthalmos and upward bowing of the orbital roof with air entrapment under the upper eyelid as previously described for SBS. Genetic analysis showed a 2q polymorphism. During follow-up, the cornea showed absence of epithelial damage and the upper eyelids were lowered symmetrically, with a regular contour.
Our HSS patient shares features with SBS. We postulate that SBS could include more than one pattern, ie, an acquired form following ventriculoperitoneal shunting and this newly reported congenital form in our HSS patient in whom typical syndromic skull anomalies led to this condition. The surgical treatment has been effective in restoring an appropriate lid level, with good globe apposition and a good cosmetic result.

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CASE REPORT
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http://dx.doi.org/10.2147/OPTH.S21333
Hallermann–Streiff syndrome with severe
bilateral enophthalmos and radiological
evidence of silent brain syndrome:
a new congenital silent brain syndrome?
Paolo Nucci1
Carlo de Conciliis2
Matteo Sacchi1
Massimiliano Serafino1
1Eye Clinic, San Giuseppe Hospital,
University of Milan, 2Eye Clinic,
Istituto Auxologico Italiano,
Milan, Italy
Correspondence: Matteo Sacchi
Eye Clinic, San Giuseppe Hospital,
University of Milan, Via San Vittore 12,
Milan 20123, Italy
Tel +39 02 5032 3150
Fax +39 02 5032 3150
Email teosacchi@excite.it
Background: We present the first case of a congenital form of silent brain syndrome (SBS) in
a young patient affected by Hallermann–Streiff syndrome (HSS) and the surgical management
of the associated eyelid anomalies.
Methods: HSS signs were evaluated according to the Francois criteria. Orbital computed
tomography (CT) and genetic analysis were performed. An upper eyelid retractor-free recession
was performed. Follow-up visits were performed at day 1, weeks 1 and 3, and months 3, 6, 9
(for both eyes), and 12 (for left eye) after surgery.
Results: The patient exhibited six of the seven signs of HSS. Orbital CT showed bilateral
enophthalmos and upward bowing of the orbital roof with air entrapment under the upper
eyelid as previously described for SBS. Genetic analysis showed a 2q polymorphism. During
follow-up, the cornea showed absence of epithelial damage and the upper eyelids were lowered
symmetrically, with a regular contour.
Conclusion: Our HSS patient shares features with SBS. We postulate that SBS could include
more than one pattern, ie, an acquired form following ventriculoperitoneal shunting and this
newly reported congenital form in our HSS patient in whom typical syndromic skull anomalies
led to this condition. The surgical treatment has been effective in restoring an appropriate lid
level, with good globe apposition and a good cosmetic result.
Keywords: Hallermann–Streiff syndrome, silent brain syndrome, upper eyelid entropion
Introduction
This case report describes the ophthalmologic features of a four-year-old child with
Hallermann–Streiff syndrome (HSS) presenting also with a condition very similar to the
so-called “silent brain syndrome” (SBS), with severe bilateral enophthalmos, bridging
of all the tarsal plates off the ocular surface, and secondary upper eyelid entropion,
retraction, and lagophthalmos. We describe the clinical appearance of the patient and
the surgical management of the associated upper eyelid retraction and entropion. To
our knowledge, this is the first report of a congenital SBS and surgical management
of the upper eyelid entropion in a young patient affected by HSS.
Case report
The child was delivered at 36 weeks because of fetal distress occurring as a result of a
lack of amniotic fluid. The parents’ marriage was nonconsanguineous. The child was
hospitalized for 36 days in the neonatal intensive care unit. General examination of the
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head and the face reveled the following signs: abnormalities
of the skull with hypoplastic mandible, micrognathia, frontal
bossing; a beak-shaped nose; abnormalities of the eye, with
microblepharon, flat orbits, and enophthalmos; atrophy
of the skin over the nose and the eyelids associated with
hypotrichosis of the scalp; and dental anomalies including
malocclusion, caries, and malformed teeth. The cycloplegic
refractive error was +1.50 in both eyes. A diagnosis of HSS
was made on the basis of the criteria reported by Francois.1
Ocular adnexal examination revealed a microblepharon
with bilateral upper eyelid retraction, entropion, and bridging
of the tarsal plates off the ocular surface. Preoperatively, the
distance between the upper lid and the apex of the corneal
limbus was 6 mm. There was also marked orbital fat atrophy
with relative enophthalmos. The upper fornix was unusu-
ally deep (Figure 1A) with copious accumulation of thick
mucopurulent discharge (Figure 1B).
Because of epiphora, nasolacrimal duct probing was
performed. The probing revealed bilateral congenital
nasolacrimal duct atresia, as reported in other craniofacial
malformations. The upper eyelid retraction, lagophthalmos,
and inverted eyelashes caused a severe traumatic keratopa-
thy with serious epithelial corneal damage and copious
filamentary secretion. Corneal involvement produced pain,
burning, foreign body sensation, tearing, blurred vision, and
severe photophobia. Visual acuity was 20/100 and 20/200 in
the right and left eye, respectively. Ocular motility was
within normal limits. Mental development was reported
to be normal. Genetic analysis, and an orbital and cerebral
computed tomography (CT) scan were performed before
surgery.
Transnasal fiberscope examination of the upper airway
was performed before surgery in order to investigate the
upper airway anatomy. The examination revealed nasal cavity
restriction, macroglossia, and epiglottic hypoplasia. General
anesthesia and intubation were uneventful. A recession and
extirpation of the levator aponeurosis and Muller muscle were
performed through an anterior lid crease approach.
The eye most seriously affected by corneal damage was
treated first. The second eye was treated after 3 months
(to properly assess the results of the first surgery, and because
the mother was pregnant with a second baby and delivery
was scheduled 1 month after the first surgery). The inci-
sion was made at the pre-existing upper lid crease, about
5 mm from the eyelid margin. Dissection was carried out in
the sub-orbicularis oculi muscle plane downward until the
tarsal plate was exposed, and upward to the orbital septum
which was opened to expose the levator aponeurosis and
to release it completely from the septum itself. The levator
aponeurosis and Muller muscle were dissected free from the
upper tarsal margin and from the underlying conjunctiva for
several millimeters almost up to the upper fornix. Care was
taken to leave the conjunctiva intact. The free edge of the
retractor complex was allowed to retract freely and then cut
for about 2 mm in order to avoid reattachment on the tarsal
plate. Skin closure was performed with three interrupted 6-0
Vicryl absorbable sutures. The surgery lasted 45 minutes. The
surgery and general anesthesia were uneventful.
Follow-up visits were performed at day 1, weeks 1 and
3, and months 3, 6, 9 (for both eyes), and 12 (for left eye)
after surgery to monitor the condition of the cornea, eyelid,
and eyelash position, as well as the patient’s symptoms after
surgery.
Results
According to the criteria described by Francois,1 our patient
had six of the seven signs of HSS (bird-like facies, abnormal
dentition, hypotrichosis, atrophy of skin especially on the
nose, bilateral microphthalmia, and proportionate short
stature). Other authors have reported six main signs and
supplementary findings as criteria for diagnosis of HSS.2
According to these criteria, our patient had five of the six
signs of the syndrome. On the basis of these findings, we
opted for a diagnosis of HSS.
Orbital CT showed bilateral enophthalmos and upward
bowing of the orbital roof, with air entrapment under the
AB
CD
Figure 1 (A) Unusually deep upper fornix. (B) Orbital computed tomography
showing bilateral enophthalmos and upward bowing of orbital roof with air
entrapment (red arrows) under upper eyelid. (C) Copious amounts of mucopurulent
discharge from upper fornix. (D) Cerebral computed tomography showing mild
enlargement of lateral ventricles.

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Congenital silent brain syndrome
upper eyelid (Figure 1B) as previously described for SDS
by Bernardini et al.3 Cerebral CT showed a mild enlarge-
ment of the lateral ventricles without signs of intracranial
hypertension. Genetic analysis showed a 2q polymorphism
in the proband and the parents proved to be carriers of the
same polymorphism. They were clinically normal, without
apparent phenotypical anomalies.
At the 9-month (for both eyes) and 12-month (for left eye)
follow-up visits, the cornea showed complete absence of
epithelial damage, as evidenced by a negative fluorescein
stain. The upper eyelid were lowered symmetrically with a
regular contour, and the eyelashes were not longer touching
the cornea (Figure 2B). Visual acuity improved to 20/20 in
both eyes. The corneal epithelial damage-related symp-
toms of pain, foreign body sensation, and photophobia had
completely disappeared.
Discussion
Hallermann–Streiff syndrome
HSS is a rare genetic syndrome primarily characterized by
head and facial abnormalities. The first report of HSS was
published by Aubry in 1893 (as cited in Warkany).4 HSS was
eventually described by Hallermann in 1948 and by Streiff
in 1950. More than 150 cases have been published up to
1982.5 In 1958, Francois reported seven essential signs for
diagnosis of HSS.1 The appearance of HSS probably results
from an asymmetric second branchial arch defect arising
during the fifth or sixth gestational week.6 Genetic analysis in
our patient showed a common and not significant or specific
polymorphism. Other genetic anomalies have been reported
previously. A report in 1980 described an elongation of one
of the arms of chromosome 10.7 Pugliese et al found a 16qh+
polymorphism in an infant with HSS.8 Pizzuti et al reported
genetic analysis of a patient with an overlapping HSS/ocu-
lodentodigital dysplasia phenotype showing a homozygous
GJA1 mutation,9 while analysis of a patient with a full-blown
HSS phenotype did not show any mutation in the GJA1
coding sequences. The author concluded that HSS can be a
genetically heterogeneous disorder.
Respiratory suppression is one of the most serious
complications in HSS patients, and problems with intuba-
tion and tracheotomy are described due to upper airway
obstruction, glossoptosis, micrognathia, and abnormal
glottis closure. Early death due to respiratory complications
is known to occur in these patients.10 Orotracheal intubation
difficulty, upper airway obstruction, and respiratory depres-
sion during general anesthesia has been described in the
literature in patients with HSS.11–13
Upper eyelid retraction
Our patient showed bilateral congenital upper eyelid retrac-
tion with inverted eyelashes and entropion. This is the first
report of this condition in a HSS patient. Upper eyelid retrac-
tion is an ophthalmological condition most frequently associ-
ated with Graves ophthalmopathy.14 Other published reports
describe upper eyelid retraction associated with blow-out frac-
ture of the orbit,15–17 following periorbital contusion without
fracture,18 after ocular surgery,19 in patients with neurogenic
disease20 and associated with contralateral blepharoptosis.21
Cruz et al reported two cases of unilateral upper eyelid cica-
tricial retraction in patients with encephalocraniocutaneous
lipomatosis.22 Bartley recently proposed a classification
system for eyelid retraction based on three categories, ie,
neurogenic, myogenic, and mechanical.20
Few data are published in the literature about upper eyelid
retraction in children. The etiologies known for this condi-
tion in children are described by Stout et al, who reported
11 cases of unilateral and five cases of bilateral eyelid
retraction. The causes of monolateral cases were congenital
aberrant innervation of the third nerve, levator fibrosis,
hemangioma, hyperthyroidism, craniosynostosis, and Down
syndrome. Bilateral eyelid retraction was associated with
either hyperthyroidism or bilateral optic nerve anomalies and
vertical nystagmus.23 Spierer and Bourla reported four cases
A
B
Figure 2 (A) Preoperative and postoperative features in the right and in the left
eye, respectively, at 3 months. (B) Postoperative features in the right and in the left
eye respectively at 9 and 12 months.

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Nucci et al
of congenital unilateral and bilateral upper eyelid retraction
without other ocular or systemic pathology.24 In our patient,
the upper eyelid retraction and entropion was probably related
to the dysfunctional relationship between eyelid and globe.
The globe has a more posterior position due to orbital fat
atrophy, microphthalmos, and enlargement of the orbit due to
the upward bowing of the orbital roof and does not properly
support the upper eyelid edge.
Silent brain syndrome
An acquired form of bilateral enophthalmos has been
described in young patients whose only systemic association
was a congenital hydrocephalus treated with a ventriculoperi-
toneal shunt.25 The upper eyelids show poor globe apposition
owing to the recessed position of the globe, as in our patient.
Orbital CT scan showed marked enophthalmos and some
air trapped between the upper eyelid and globe. Cerebral
CT showed dilated ventricles. These CT findings were also
seen in our patient.
Most recently, Bernardini et al reported two cases of
gross acquired bilateral enophthalmos following childhood
hydrocephalus treated by ventriculoperitoneal shunting.3
The patients had enophthalmos with bridging of the eyelid
away from the ocular surface, and CT scans showed marked
upward bowing of the orbital roof and air entrapment
under the upper eyelids. The mechanism speculated for
this condition is a sudden reduction of raised intracranial
pressure causing an implosion of the only thin cranial bone,
ie, the orbital roof. This upward bowing of the roof leads
to a progressive enophthalmos. The authors referred to this
condition as SBS.
Conclusion
Our HSS patient had features of SBS, showing bilateral
congenital enophthalmos with poor apposition between the
upper eyelid and globe, upper eyelid retraction with entropion,
and an unusually deep upper fornix with copious discharge.
A mild form of hydrocephalus without signs of intracranial
hypertension was present, consistent with previous reports
of this condition. We postulate that this disorder could be
a clinical entity including several clinical patterns, ie, the
acquired form following ventriculoperitoneal shunting,
where remodeling of the cranial bone seems to lead to the
characteristic clinical and radiological changes, and this newly
reported congenital form in our HSS patient, in whom typical
syndromic skull and orbit anomalies (flat orbits, enophthalmos,
and microphthalmos) led to the condition. In its congenital
form, it is not clear if the relative enophthalmos is caused by
the marked bony anomalies or if they are caused by relative
intracranial hypotension during fetal development, similar to
what happens in the acquired post ventriculoperitoneal shunt
variant. Surgical treatment of the severe keratopathy caused
by the upper eyelid anomalies and inverted eyelashes has so
far been very effective in restoring an appropriate lid level
with good globe apposition, thus completely resolving the
underlying corneal problems with a good cosmetic result in
this patient with HSS and a congenital form of SBS.
Disclosure
The authors report no conflicts of interest in this work.
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