Julie Mortier1, Daša Gluvajić2
stridor in an infant with Multiple Pterygium
syndrome: a Case report
Stridor pri novorojenčku s sindromom večkratnih pterigijev: prikaz
primera
aBstraCt
KEY WORDS: multiple pterygium syndrome, Escobar syndrome, webbing, arthrogryposis, bilateral vocal
fold immobility
Multiple pterygium syndrome is a very rare congenital inherited condition. The clini-
cal presentation involves joint contractures and excessive webbing (pterygia). The
disease exists in two forms differentiated by severity: lethal multiple pterygium syndrome
and the non-lethal milder Escobar syndrome. In patients with Escobar syndrome, web-
bing usually occurs on the skin of the neck, fingers, forearms, inner thighs, and back of
the knees. This case report intends to describe the laryngological features of the Escobar
syndrome, the work-up and approach in the case of an affected neonate presenting with
congenital stridor, multiple webbing, joint contractures, and feeding difficulties.
iZvleČek
KLJUČNE BESEDE: sindrom, Escobarjev sindrom, pterigij, artrogripoza, obojestranska okvara gibljivosti
glasilk
Sindrom večkratnih pterigijev je zelo redka dedna bolezen. V klinični sliki se kaže s šte-
vilnimi skrčenji sklepov in nastankom pterigijev. Bolezen obstaja v dveh oblikah, ki se
razlikujeta glede na klinični potek: letalna oblika sindroma in Escobarjev sindrom, ki ima
lažji klinični potek. Pri bolnikih z Escobarjevim sindromom pterigiji nastanejo na koži
vratu, med prsti, na notranjosti rok in nog ter za koleni. V prikazu primera predstavlja-
mo laringološke posebnosti, ki se lahko pojavijo pri Escobarjevem sindromu, in opisu-
jemo klinični pristop k diagnostični obravnavi novorojenčka s kongenitalnim stridorjem,
številnimi pterigiji, sklepnimi skrčenji in motnjo hranjenja.
1 Julie Mortier, dr. med., Oddelek za otorinolaringologijo, Univerzitetna bolnišnica Antwerp, Drie Eikenstraat 655,
2650 Edegem, Belgija
2 Asist. Daša Gluvajić, dr. med., Klinika za otorinolaringologijo in cervikofacialno kirurgijo, Univerzitetni klinični center
Ljubljana, Zaloška cesta 2, 1000 Ljubljana; dasa.gluvajic@kclj.si
445Med Razgl. 2022; 61 Suppl 2: 445–451
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introDUCtion
In the last few decades, over 150 different
conditions have been identified as the cause
for congenital contractures. All of them
are quite rare (1). On the basis of observed
malformations, multiple pterygium syn-
drome (MPS) was first described in 1902,
but was not identified as a distinct syndro-
me until 1978 (2). The phenotypic features
are extensive webbing across major joints
and contractures, small stature, minor facial
anomalies, ptosis of eyelids, inner canthal
folia, micrognathia with downturning cor-
ners of the mouth, limb anomalies, finger
contractures, camptodactyly, syndactyly,
equinovarus and/or rocker bottom feet, sco-
liosis, vertebrae and/or rib anomalies, and
genital anomalies like cryptorchidism and
absence of labia majora (3).
Case Presentation
We present a firstborn child of a non-con-
sanguineous couple, in whom fetal ultra-
sound identified an aortic valve stenosis and
increased nuchal translucency. An amnio-
centesis and karyotyping were performed in
the 16th week of pregnancy and the results
showed a normal male karyotype. Shorter
leg bones were additionally identified on
the morphologic ultrasound. Further gene-
tic testing was performed, but initially
suspected autosomal dominant achondro-
plasia was not identified. The pregnancy was
terminated in the 40th week by Caesarean
section because of a breech neonatal posi-
tion. Birth was uncomplicated (appearan-
ce, pulse, grimace, activity and respiration
(APGAR) 8/8, weight 2,990 g, body length
43 cm, head circumference 37 cm), and the
child’s mother’s tests for hepatitis B virus
infection and toxoplasmosis were negative.
otorhinolaryngological
examination
The child had inspiratory and biphasic
stridor at birth, as well as tachypnea. Breath
sounds were more pronounced when agi-
tated. Nasal continuous positive airway
pressure (CPAP) was initially applied, how-
ever, he had desaturation spells up to 70%
SpO2 (saturation of oxygen) in cases of
distress with agitation and crying. After five
days on CPAP, the Airvo™ nasal high-flow
system (8 l O2/min and 21% O2) was ini-
tiated successfully.
A nasolaryngoscopy and bronchoscopy
under general anesthesia and spontaneous
breathing were performed 14 days after
birth. These examinations showed that the
nasal cavity and choanae were patent, there
was no adenoid hypertrophy and the epi-
glottis had a normal shape. Vocal folds were
white and smooth but in an adducted para-
median position and there was no visible
abduction on inspiration. Mild inspiratory
collapse of the arytenoid mucosa was
observed, the subglottis was normally sha-
ped and there was no tracheomalacia. An
X-ray of the thorax did not show pulmonary
abnormalities.
An awake nasolaryngoscopy 27 days
after birth showed a paramedian position
of the vocal folds, with adduction of folds
during crying, but no abduction movement
on inspiration. There were no signs of laryn-
gomalacia. Nocturnal polygraphy was per-
formed with the Airvo™ high-flow system
(8 l O2/min and 21% O2). It showed a nor-
mal breathing and heart rate for the age,
mean SpO2 98% (range: 95–98%), no cen-
tral apneas and an apnea–hypopnea index
(AHI) of 1/hour. The child was discharged
with the Airvo™ high flow system (8 l O2/
min and 21% O2) that he used during the
day and at night time. Regular nocturnal
polygraphies were performed. Based on
the results without the Airvo™ system at
the age of seven months (breathing fre-
quency 26–32/min, mean SpO2 98% and
range: 95–100%, heart rate 115–125/min,
AHI 1/hour), a period of only nocturnal use
of Airvo™ was suggested. Re-evaluation of
nocturnal polygraphy without the Airvo™
system after six months showed no sleep-
446 Julie Mortier, Daša Gluvajić stridor in an infant with Multiple Pterygium syndrome: a Case report
ORL 2022_Mr10_2.qxd  2.9.2022  13:00  Page 446
related breathing disorder (breathing fre-
quency 28–30/min, SpO2 mean 97% and
range: 96–99%, heart rate 90–105/min,
AHI 0/hour), therefore, Airvo™ support
was stopped. Yearly follow-up polygraphies
remained good.
Feeding difficulties were initially ob-
served with easy fatigue. Placement of
a nasogastric feeding tube was indicated
because of failure to thrive. A fiberoptic
endoscopic evaluation of swallowing (FEES)
at two months of age showed no patholo-
gical swallowing function or aspiration
and oral feeding rehabilitation was suc-
cessfully initiated. A combination of oral
and nasogastric tube feeding was necessary
until the age of four months.
Disease Presentation
Multidisciplinary assessment was carried
out, concerning (4):
• cardiology:
• Bicuspid aortic valve stenosis (gradient
30 mmHg) was successfully dilated
(balloon dilation) at two months of age.
Ibuprofen conservative therapy for
Bottal duct closure was successful.
• neurology:
• General hypotonia was described with
minimal spontaneous movement of
the limbs. Facial expressions were mini-
mal, but there was no facial muscular
paresis. Limb reflexes were absent.
• Head ultrasound and electroencepha-
logram (EEG) were normal.
• Bilateral vocal fold immobility (BVFI)
can be a sign of an underlying syste-
mic neurologic condition. MRI scan
would be useful in detecting such
a cause. Based on the nasolaryngo-
scopic findings, which showed normal
adduction of vocal folds, a neurologi-
cal cause was improbable.
• gastro-enterology:
• Ultrasound showed abdominal meteo-
rism with normal peristalsis and ana-
tomic structures.
• urology:
• The patient underwent surgery for
a left-sided inguinal hernia and bila-
teral cryptorchidism.
• genetic assessment:
• Facial features: high nasal root, mild
hypertelorism, downward slant eyes,
ptosis of the right upper eyelid, nor-
mal iris, blepharophimosis, epicantus
inversus, high arched palate without
palatal schisis, small jaw, low set ears.
Short neck with webbing and fibro-
matosis was documented on ultra-
sound. Webbing of skin was present in
the axillae, elbow and inguinally.
• Metabolic disorders were absent.
• At the first genetic assessment based
on clinical features, MPS or Freeman-
Sheldon syndrome was suspected.
Genome sequencing showed two gene-
tic variants of the Cholinergic Receptor
Nicotinic γ-Subunit gene (the CHRNG
gene ). One variant (c. 753–754del) is
a known pathologic gene variant, the
other (c. 250G>A) is a gene variant of
unknown function. The child has inhe-
rited one variant from each parent.
Based on the genetic testing and the
clinical signs the most probable dia-
gnosis is MPS Escobar type.
DisCUssion
The diagnosis of arthrogryposis or multi-
ple joint contractures (as seen in MPS) can
usually be made on a prenatal ultrasound.
The most common detailed findings are
fixed flexion joint deformities, microgna-
thia, altered amniotic fluid volume, limb
deformities, cerebral ventriculomegaly,
dysmorphic features, and growth retardation
(5). The classic facies of MPS shows micro-
gnathia, short and webbed neck, low set ears,
long philtrum and downturning mouth (6).
In children with arthrogryposis, airway
anomalies such as vocal fold immobility,
glossoptosis, supraglottic narrowing and
laryngomalacia have been described with
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a high risk of airway compromise. Dysphagia
is common with possible aspiration pneu-
monia and poor nutrition (7). 
Stridor is an abnormal audible high-
pitched breath sound, resulting from a par-
tially obstructed or stenotic upper airway.
It is a warning sign of potentially dange-
rous underlying airway disease and must
be investigated. Generally, the main causes
of congenital stridor are laryngomalacia,
vocal fold immobility, congenital subglot-
tic stenosis, laryngeal webs, tracheomalacia
and subglottic hemangioma. Laryngomalacia
accounts for 60–70% of cases, and BVFI is
the second most common cause. Unilateral
vocal fold immobility is usually due to
recurrent laryngeal nerve injury during
birth, surgical trauma or compression from
mediastinal masses, while BVFI results
from neurological disorders (8).
The manifestation of interest in the pre-
sented clinical case is BVFI, not initiated by
a neurologic cause but probably due to an
underlying fixation of the cricoarytenoid
joints in a patient with arthrogryposis. BVFI
is a recognized source of stridor and respi-
ratory distress, and a vocal fold in a para-
median adducted position can present as
a medical urgency at birth that leads to stri-
dor and breathing difficulty (9).
A careful diagnostic evaluation needs
to be done when facing a child with MPS
and BVFI (10).
Many practitioners examine the upper
airways of a child with an awake flexible
nasolaryngoscopy, however, an examination
under general anesthesia provides the
opportunity for better visualization of the
entire airway system. A flexible nasola-
ryngoscopy or bronchoscopy and a direct
rigid laryngoscopy can be performed. These
enable the visualization of the airway
during sedation and spontaneous breathing.
A dynamic obstruction in the upper airway
and movement of the vocal folds during
breathing can be visualized on a flexible
nasolaryngoscopy. Direct rigid laryngos-
copy is the method of choice to diagnose
the presence of laryngotracheal clefts, and
in cases of BVFI, allows palpation of the ary-
tenoids to assess the mobility of the cri-
coarytenoid joints. After the diagnostic
endoscopy, it is possible to proceed with
surgical intervention if needed during the
same procedure. Therefore, a combination
of flexible and rigid endoscopy is often per-
formed (11).
Laryngeal electromyography is a well-
established instrument for evaluating adult
patients with cricoarytenoid joint dys-
function. It is an adjunct to the clinical inve-
stigations and palpation of arytenoids
under direct laryngoscopy, mostly useful in
recurrent laryngeal nerve damage, cen-
trally correctable lesions, and idiopathic
BVFI (7, 12).
In general, when confronted with a patient
with BVFI, an MRI is used to evaluate the
brain and spinal cord, in case an underlying
neurological or cerebral condition is suspec-
ted (3).
Mutations in the CHRNG gene can
result in both the non-lethal Escobar variant
MPS, and the lethal MPS (fatal in 2nd or 3rd
trimester). Lethal MPS follows an autoso-
mal and an X-linked recessive inheritance
pattern (13). The CHRNG gene provides
instructions to make the γ-protein compo-
nent (subunit) of the acetylcholine recep-
tor (AChR). The AChR is found in the
membrane of skeletal muscle cells and is
critical for signaling between nerve and
muscle cells, which is necessary for move-
ment. A lack of signaling results in the inac-
tivation of the muscular neural motor
plate, leads to akinesia, and joint contrac-
tures (with pterygia) before birth, and may
also result in cricoarytenoid fixation. In con-
trast to other forms of BVFI, this is a direct
result of restricted joint motion (14, 15).
Only a few articles describe patients
with Escobar syndrome requiring a tra-
cheotomy for upper airway obstruction (6,
10, 16, 17). According to Shen et al., a trac-
448 Julie Mortier, Daša Gluvajić stridor in an infant with Multiple Pterygium syndrome: a Case report
ORL 2022_Mr10_2.qxd  2.9.2022  13:00  Page 448
heotomy for patients with BVFI due to
cricoarytenoid fixation as seen in MPS
should be considered when endotracheal
intubation is necessary to keep airway
patency, extubation is unsuccessful, or
when severe complications related to BVFI
and chronic respiratory insufficiency such
as failure to thrive or recurrent aspiration
pneumonia are present (18).
In idiopathic cases unrelated to MPS,
more than 50% of children with BVFI will
have a spontaneous resolution in the first
12 months of life (19). It is unclear whether
this is the case in arthrogryposis. Recovery
rates are unavailable in literature, but
based on the etiology of cricoarytenoid arti-
culation immobility, a full spontaneous
recovery is usually not expected.
Watchful waiting can be considered in
certain cases of BVFI. Non-invasive venti-
lation support techniques, such as CPAP and
nasal high flow therapy systems have been
successfully used in cases of dynamic mild
airway obstruction, like in the presented cli-
nical case (19).
Endoscopic suture lateralization of one
or both vocal folds with arytenoid abduc-
tion has been described in children and
adults. Endoscopic arytenoid abduction
lateropexy with alaryngeal suture is a quick,
reversible, minimally-invasive vocal fold
lateralizing technique, used for enlarging
the posterior glottis. The arytenoid cartilage
is lateralized to a normal abducted position.
It might be a favorable option for neona-
tes, since airway patency can be achieved
in one step without irreversible damage to
the glottic structures, and it can even be
a long-term solution (20).
However, different strategies and sur-
gical techniques to increase the glottis
area have emerged. Although they would
possibly prevent tracheostomy, they invol-
ve a greater risk of laryngeal sequelae and
postoperative aspiration or dysphonia.
Cordotomy with or without arytenoidec-
tomy has been often used in adults with
BVFI and has been described in children as
well. The procedure consists of an incision
in the posterior third of the true vocal fold
with a further partial or total arytenoi-
dectomy. The procedure is irreversible, and
an adverse effect on the voice is expected
(19, 21).
Recently, new endoscopic procedures
have additionally emerged, like the endos-
copic anterior and posterior cricoid split
(22). First, the posterior cricoid is incised
using a laryngeal knife or CO2 laser. Next,
the anterior cricoid is incised through
a mucosal incision made with a sharp sic-
kle knife while exercising caution to avoid
injury to the anterior commissure. After
completing the anterior and posterior split,
a non-compliant balloon is placed through
the glottis and is expanded to put pressu-
re and dilate the cricoid plate. The patient
is then intubated with a half-size larger than
the age-appropriate endotracheal tube for
a period up to two weeks. After extubation,
additional balloon dilation is performed if
needed (23). Furthermore, isolated endos-
copic balloon dilation has been described
as a successful treatment approach in cases
of laryngeal stenosis. During the procedu-
re, a telescope and the balloon catheter are
introduced into the laryngeal lumen and
dilated. A series of balloon dilations is
usually needed, and in some cases the bal-
loon itself could cause a partial cricoid split
(24). Endoscopic and open approach poste-
rior cricoidotomy and cartilage grafting for
laryngeal lumen augmentation have been
described in isolated posterior glottic ste-
nosis and in BVFI (25, 26).
ConClUsions
We have presented a rare case of congeni-
tal stridor caused by BVFI with cricoary-
tenoid joint fixation in a neonate with
arthrogryposis in MPS. Congenital stridor
is an abnormal audible high-pitched breath
sound and results from a partially obstruc-
ted or stenotic upper airway. It is always
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a warning sign of a dangerous underlying
disease and must be investigated imme-
diately. Stridor can be the presenting com-
plaint in children with arthrogryposis, and
early recognition of airway obstruction and
feeding problems will avoid life-threatening
complications and further developmental
delay. Any procedure to establish a patent
airway should ideally have a minimal impact
on the ability to phonate and swallow. A con-
servative, but successful treatment approach
should be used. Different surgical techni-
ques to increase the glottis area in BVFI can
be used to avoid tracheostomy, which has
been the standard of care for a long time
and is mandatory in cases of threatened air-
way and respiratory distress. 
450 Julie Mortier, Daša Gluvajić stridor in an infant with Multiple Pterygium syndrome: a Case report
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