TITLE: The Syndromal Child
SOURCE: Grand Rounds Presentation, UTMB, Dept. of Otolaryngology
DATE: May 16, 2001
RESIDENT PHYSICIAN: Michael Underbrink, MD
FACULTY PHYSICIAN: Ronald Deskin, MD
SERIES EDITOR: Francis B. Quinn, Jr., MD
"This material was prepared by resident physicians
in partial fulfillment of educational requirements established for the
Postgraduate Training Program of the UTMB Department of Otolaryngology/Head and
Neck Surgery and was not intended for clinical use in its present form. It was
prepared for the purpose of stimulating group discussion in a conference
setting. No warranties, either express or implied, are made with respect to its
accuracy, completeness, or timeliness. The material does not necessarily
reflect the current or past opinions of members of the UTMB faculty and should
not be used for purposes of diagnosis or treatment without consulting
appropriate literature sources and informed professional opinion."
As otolaryngologists, we are often involved in the management of children with congenital disorders that affect the head and neck, i.e., craniofacial syndromes. Our consultation is frequently required when inborn anatomic or physiologic problems affect respiration, swallowing, hearing, speech or facial appearance. Therefore, the otolaryngologist should be familiar with the basic terminology used in syndrome diagnosis and the specific otolaryngologic issues involved with congenital anomalies affecting the head and neck.
Definitions:
Malformations
A malformation is defined as a
morphologic defect of an organ, part of an organ, or larger area of the body,
which results from an intrinsically abnormal developmental process. Malformations can be relatively simple or
complex depending on when the defect is initiated during development. If the defect is initiated early in
development the consequences are far more severe. Examples of malformations include cleft palate, syndactyly, and
renal agenesis.
Deformations
A deformation is defined as an abnormal form or position of a body part
caused by nondisruptive mechanical forces.
These abnormalities occur more frequently late in fetal development and
may result from mechanical, malformational or functional causes. The common underlying pathology is a result
of restricted movement by the fetus.
The most common causes are a result of mechanical forces, such as
unstretched uterine and abdominal muscles, small maternal size, anmiotic tears,
abnormal uterine anatomy and twin fetuses.
Deformations may also result from malformations that affect fetal
movement. When this occurs, the
malformations usually involve the central nervous system and the urinary
tract. An example of a complex malformation-deformation
relationship is Potter or oligohydramnios sequence. The compression deformities of the face and limbs, pulmonary
hypoplasia, and growth restriction result from any condition that leads to oligohydramnios
(i.e., bilateral renal agenesis, polycystic kidneys, urinary tract obstruction,
or amnion leakage).
Disruptions
A disruption is defined as a defect of an organ, part of an organ, or a
larger area of the body due to interference with an otherwise normal
developmental process. Disruptions tend
to occur sporadically and rarely, unlike malformations and deformations that
tend to recur. An example of a
disruption is the formation of amniotic bands, which may lead to digit/limb
amputations, bizarre facial clefting, or large calvarial defects.
Sequence
A sequence may be defined as multiple defects that occur as a result of
a single presumed structural anomaly.
The primary defect starts a chain of events, which affects the
subsequent development of an organ or larger body part. For example, mandibular deficiency seems to
be the initiating factor in the Pierre Robin sequence. The relative retroposition of the mandible
maintains the tongue high in the nasopharynx, which prevents normal fusion of
the palatal shelves. Malformations and
sequences are nonspecific and may occur as an isolated event or as a component
of various syndromes.
Syndrome
A syndrome is a pattern of multiple anomalies believed to be
pathogenetically related and not representing a sequence. Furthermore, a syndrome usually implies a
single etiology for an associated group of anomalies. In syndromes, the pathogenesis of a group of malformations is
frequently less understood than in a sequence.
Also, because the malformations that are associated with syndromes occur
in embryonically noncontiguous areas, they must be related at a more basic
level. Hence, hereditary disorders are
usually described as syndromes, because the phenotype is due to a single
genetic defect.
Association
An association is the nonrandom
occurrence in multiple individuals of a group of anomalies that are not known
to be a sequence or syndrome. Examples
include CHARGE (colobomas, heart defects, atretic choanae, retarded growth,
genitourinary anomalies, and ear malformations) and VATER (vertebral defects,
anal atresia, tracheo- esophageal fistula/atresia, and radial anomalies). Although associations are not specific
syndromes or diagnoses, the mnemonics help to alert clinicians to search for
associated anomalies in these patients.
Approach to Syndrome
Diagnosis
There are over 3,000 genetic syndromes described to date, so it would
be impossible for a clinician to recognize all but the most common. Therefore, one should always simplify things
by beginning with a good history including a detailed medical pedigree. Information should be solicited about
maternal and paternal ages, parental consanguinity, previous abortions and
maternal exposure to teratogens. It is
also helpful to compare siblings and other family members when possible. During physical examination, one should
search for both major and minor anomalies, especially of the auricles and
facial features. It is always useful to
search reference books, such as Smith’s
Recognizable Patterns of Human Malformations, to help identify a suspected
syndrome. If a syndrome is strongly
suspected, a geneticist should be consulted to evaluate the patient for
appropriate laboratory tests and karyotyping.
This will also ensure that the parents receive appropriate genetic
counseling.
Management Issues of the
Syndromal Child
Children with craniofacial
abnormalities have multiple aesthetic, functional, and psychological concerns,
which are best managed by a team of specialists. The otolaryngologist on the team is responsible for the assessment
and management of the upper airway, hearing and speech in these children.
Airway Obstruction:
Children with craniofacial anomalies present a variety of airway
challenges to the otolaryngologist. The
effects of the airway obstruction may be related to age, and often change as
the child grows. Often these children
represent difficult airway maintenance during necessary surgical procedures,
which can be a significant cause of morbidity and mortality.
Neonatal Nasal Airway
Obstruction
Neonates are obligate breathers until about age 3 months. Therefore, when the nasal passages become
obstructed, they experience respiratory distress, becoming cyanotic, when their
mouths are closed or during feeding.
This problem commonly occurs with bilateral choanal atresia and children
with midface hypoplasia (Crouzon/Apert syndrome). The problem is usually relieved with a secured oral airway until
at least 3 months of age.
Neonatal Oropharyngeal
Airway Obstruction
Neonates can also experience respiratory distress when the tongue falls
back into the oropharynx. This is
common in neonates with retrognathia or micrognathia, and the resultant
glossoptosis. This problem causes more
problems when associated with a cleft palate, as in Pierre Robin sequence. This type of airway obstruction usually
responds to nursing the infant in the prone position for the first few months
of life. If symptoms persist, insertion
of a nasopharyngeal airway or tracheotomy may be necessary. When the child approaches 6 months of age,
mandibular growth is usually sufficient to decrease the glossoptosis and
resolve the obstruction. Decannulation
can be performed at this time or usually shortly after palatoplasty (with cleft
palates).
Obstructive Apnea
Children with craniofacial anomalies may experience obstructive apneic
episodes during sleep due to a variety of causes, including maxillary
hypoplasia with a resultant narrow nasopharyngeal airway (Crouzon and Apert
syndromes), retrognathia (Treacher Collins syndrome), and palatopharyngoplasty
performed in a child with velopharyngeal incompetence (VPI) and glossoptosis
(Pierre Robin, Treacher Collins).
Children with narrow nasopharyngeal
airways, as in Crouzon syndrome, have benefited from adenotonsillectomy prior
to three years of age. Patients with
retrognathia and obstructive symptoms may benefit from tonsillectomy if the
palatine tonsils are enlarged. Children
with retrognathia or micrognathia and a history of airway obstruction are poor candidates for palatopharyngoplasty
to correct VPI. It is probably a good idea to obtain a preoperative sleep study
prior to pharyngeal surgery for VPI in any child with a clinical suspicion of
OSA.
It is often necessary in children with craniofacial anomalies and
OSA to perform a series of escalating operations to relieve the
obstruction. Each is followed by a
sleep study to determine effectiveness.
These operative procedures may include, (adeno)tonsillectomy, laser
reduction of the mid-base of tongue, uvulopalatopharyngoplasty, laser resection
of redundant supraglottic structures or pharyngeal folds, sliding mandibular
osteotomies (creating a class III malocclusion), and finally tracheotomy. It may be necessary to perform tracheotomy
early in these patients to prevent asphyxiation.
Airway Maintenance and
Craniofacial Surgery
During surgical correction of craniofacial anomalies, the airway is
maintained with endotracheal intubation (oral or nasal) or tracheotomy. The use of elective tracheotomy is less
common today because of advances in intubation equipment and techniques and
stabilization with rigid fixation of mandibular/maxillary osteotomies. However, tracheotomy should still be
considered under certain circumstances.
Tracheotomy is indicated:
1.
if
endotracheal intubation for the procedure is impossible, expected to be
difficult or traumatic, or if postsurgical extubation distress is anticipated.
2.
to facilitate surgery and postoperative care
(as with extended midfacial procedures)
3.
when
extended nasotracheal intubation, which is necessary for mandibular
osteotomies, is not possible secondary to a previous palatopharyngoplasty
In order to reduce morbidity and/or
mortality rates, tracheotomy should be performed with the airway controlled by
a bronchoscope or endotracheal tube in these patients. However, in patient’s with severe mandibular
hypoplasia (Pierre Robin, Treacher Collins, Goldenhar), intubation may be
extremely treacherous, because the larynx may be impossible to visualize with
standard intubation techniques. In such
a case, it may be necessary to first perform direct laryngoscopy with a
pediatric anterior commissure laryngoscope with insertion of the endotracheal
tube through the laryngoscope. It may
be necessary to use a small telescope as an optical stylet if visualization is
still difficult.
Hearing Loss:
Children with craniofacial anomalies have a high
risk of congenital and acquired hearing loss.
Since even mild hearing losses can significantly delay the acquisition
of language skills and intellectual development, these children require careful
otologic and audiologic follow-up and management. The detection of hearing loss is often delayed by the erroneous
belief that slower learning is somehow
related to their syndrome.
Congenital Hearing Loss
In most craniofacial anomalies the
congenital hearing loss is conductive.
Sensorineural hearing loss is thought to be coincidental if present,
except in the case of Waardenburg syndrome.
Microtia with atresia of the external auditory meatus is frequently seen
in Treacher Collins syndrome and hemifacial microsomia, and results in a
congenital conductive hearing loss.
Patients with bilateral microtia and EAC atresia often have obliteration
of the middle ear cleft, which precludes surgery. These patients often do well with hearing aids. Surgery is usually not recommended in these
patients with a normal hearing ear, and they do well with CROS (contralateral
routing of signal) hearing aids.
If the child’s ears appear normal,
conductive hearing loss may be the result of ossicular deformity or
fixation. Middle-ear surgery may
improve hearing in this subset of patients, but caution is necessary to avoid
damage to a dehiscent or abnormally located facial nerve. CT scans of the temporal bone should be
obtained prior to any surgical intervention.
Acquired Hearing Loss
Acquired Hearing Loss in children
with craniofacial anomalies is usually a consequence of eustachian tube
dysfunction (ETD). ETD is common in
children with secondary cleft palates,
however, it may also be seen in patients with craniosynostosis and the
associated anomalies of the midface and skull base. These children will usually require ventilation tubes, because
the ETD does not respond to medical management or surgical repair. There have been reports of an increased
incidence of unilateral jugular bulb dehiscence in children with
craniosynostosis, so care must be taken when performing the myringotomy. Multiple tympanostomy tube placements is
often the rule. Tympanoplasty
procedures are usually unsuccessful until late adolescence due to persistent ETD.
Speech Disorders:
Hypernasality
Hypernasality is often a consequence of VPI after cleft palate
repair. It may also be apparent as
“deaf speech”, observed in children with craniofacial anomalies and hearing loss
greater than 30dB without VPI. This
complication is often manageable with speech therapy alone. Palatopharyngoplasty may be necessary in
children over 5 years old with persistent VPI despite speech therapy.
Hyponasality
Hyponasality is usually due to some form of nasal obstruction. This can occur in children with severe
posterior displacement of the midface, bilateral choanal atresia and iatrogenic
velopharyngeal atresia (over correction with pharyngopalatoplasty). Removal of nasal airway obstruction usually
resolves the problem.
Hoarseness
Hoarseness occurs in 20 percent of children with VPI secondary to the
development of vocal cord nodules. This
is thought to be a response to compensatory laryngeal activity. With elimination of the VPI, the nodules
usually resolve. Hoarseness may also
develop after nasotracheal intubation.
Common Syndromes:
Down Syndrome (Trisomy 21)
The incidence of Down syndrome (DS) is about 1 in 700, which makes it
the most common chromosomal anomaly.
This incidence increases proportionately with maternal age, especially
older than 35 years. It was first
described in 1866 by John Landon Down, and is characterized by typical
dysmorphic facies, flat nasal bridge, epicanthal folds, speckled irides,
brachycephaly, various orofacial anomalies, a simian crease, learning
disabilities and generalized hypotonia.
Airway:
An array of congenital airway anomalies occurs in DS
patients. Because of midface
hypoplasia, the nasopharyngeal and oropharyngeal regions are narrower and of
smaller volume overall. OSA occurs in
approximately 50% of DS patients. Given
the generally small size of the adenoid pad in DS, adenotonsillectomy alone
often fails to relieve upper airway obstruction. The addition of uvulopalato-pharyngoplasty (UPPP) has been shown
to improve overall outcome. However, tracheotomy may be required in refractory
cases. The incidence of subglottic
narrowing has been found to be higher in DS than the general population. Because of this and the smaller airway
commonly seen in DS, initial intubation should be made with an ET tube 2 sizes
smaller than normally used. Another
concern during anesthesia is the increased incidence of atlantoaxial
instability in DS, which has been reported as high as 20%. Therefore, careful preoperative assessment
of the cervical spine with radiographs should be obtained to avoid injury. All DS patients should be admitted to he
hospital for postoperative observation following adenotonsillectomy.
Hearing:
Congenital and acquired otologic problems contribute
to the relatively high incidence of hearing loss in DS patients. Conductive hearing loss may be a result of
various anomalies including small pinna size, stenotic external auditory canals
(predisposes to OE and CI), eustachian tube dysfunction (COME in 60%), and
ossicular fixation. Sensorineural
hearing is less common but may result
from progressive ossification along the basal spiral tract, or other temporal
bone anomalies (mondini’s cochlea, shortened apical cochlear turns, shortened organ
of Corti, and decreased spiral ganglion cells). Management includes ventilation tubes for COME, frequent otologic
and audiologic evaluation, and hearing aids for persistent hearing loss.
Velocardiofacial Syndrome
Velocardiofacial syndrome (VCFS) was
delineated as a distinct multiple-anomaly syndrome in 1978. It may be the most common syndrome second to
Down syndrome. It is characterized by
congenital heart disease, hypernasal speech, cleft palate, learning
disabilities, and a characteristic facial appearance. The transmission is by autosomal dominant inheritance, and the
specific genetic cause is usually a deletion of chromosome 22.
The characteristic features of
facial structure influenced by basicranial angulation include vertical
maxillary excess, puffy upper eyelids, retrognathia, a prominent nasal root,
and flat malar eminences. Although the
mandible is typically structurally normal, it appears retruded because of the
skull base angulation. Vascular anomalies are probably the most common structural
malformation associated with VCFS and are present in all parts of the
body. Anomalies of the major neck
vessels are far more common, however, and have been found in almost all cases
studied with magnetic resonance angiography.
Speech:
Palatal anomalies and consequent speech disorders
are very common in VCFS. Of the palatal
clefts found in the syndrome (75% of patients), fewer than 20% are overt. About 44% of the clefts of the secondary
palate are typical submucous clefts with the classic bifid uvula, however, the
remainder are occult. In fact, without
endoscopic evidence, occult clefts in VCFS are nearly impossible to
detect. In addition, the angulation of
the skull base draws the posterior pharyngeal wall away from the palate which
further contributes to the severe hypernasality observed in VCFS. Surgery for VPI is commonly applied to
children with VCFS, but must be well planned to avoid injury to aberrant neck
vessels. Speech evaluation and therapy
must be conducted by a person with expertise in treating patients with VCFS.
Airway:
In infants with VCFS, airway obstruction is a common
problem with multiple causes. Infants
may exhibit any combination of generalized hypotonia, pharyngeal hypotonia,
retrognathia, hypertrophic arytenoids, larygomalacia, laryngeal webs, vascular
rings, anomalous subclavians, and reactive airway disease. Endoscopic assessment of the airway is
critical to determine the source or sources of obstruction. Flexible fiberoptic laryngoscopy and
bronchoscopy are often employed to sort out the potential causes. Severe upper airway obstruction requiring
tracheotomy in VCFS is rare. When there
is the combination of retrognathia, cleft palate and airway obstruction in
VCFS, the diagnosis of Robin’s sequence if often mistakenly made (11%).
Hearing:
Minor abnormalities of the ear are common in VCFS,
the most consistent variation being overfolding of the helix. Also, the pinnae and ear canals tend to be
small making otoscopic examination difficult.
Chronic middle-ear disease is common in VCFS with conductive loss in
approximately 75% because of middle ear effusion. This is related to the palatal anomalies and the frequent
immunopathy that tends to occur in these patients. In fact the course and duration of otitis in VCFS patients is
typically more severe than in other patients with cleft palates. Sensorineural hearing loss occurs in
approximately 15% of patients, but unlike other genetic disorders, it is
typically unilateral and mild.
Pierre Robin Sequence
.
The triad of cleft palate,
micrognathia, and glossoptosis (causing airway obstruction) is known as the
Pierre Robin sequence (PRS), credited to a French stomatologist who reported
the association of micrognathia with glossoptosis in 1923, later adding cleft
palate to the sequence in 1934. The
incidence most widely accepted among clinicians today is 1 in 8500. The sequence results from a series of events
leading to the triad. The initiating
event seems to be mandibular deficiency or hypoplasia which may have a variety
of causes, including positional malformation (oligohydramnios, multiple
births), intrinsic hypoplasia (genetic or teratogenic syndromes), neurologic or
neuromuscular abnormalities (decreased movement), or connective tissue
disorders. Children born with PRS have
either nonsyndromic PRS (80%) or syndromic PRS, which carries a poorer
prognosis. Syndromes most commonly
associated with PRS include Stickler (severe ocular anomalies), VCFS, Fetal
alcohol syndrome, and Treacher Collins syndrome.
Airway:
The cause of airway obstruction in PRS is
multifactorial in nature, with both anatomic and neuromuscular components. Sher describes a classification scheme based
on the four different processes he was able to identify with flexible
fiberoptic nasopharyngoscopy:
Type 1: obstruction is due to posterior movement of
the tongue contacting the posterior pharyngeal wall (true glossoptosis - 59%)
Type 2: the tongue moves posteriorly but the palate
becomes sandwiched between the tongue and velum causing nasopharyngeal
obstruction (21%)
Type 3: the lateral pharyngeal walls move medially,
apposing one another (10%)
Type 4: pharynx constricts in a sphincteric manner
(10%)
There are many proposed management strategies for
airway obstruction in PRS on the basis of a type 1 obstruction (e.g.,
positioning, mandibular traction, glossopexy, mandibular distraction
osteogenesis, subperiosteal release of the floor of mouth, nasopharyngeal
airway, and tracheotomy). However, it
is clear that types 2, 3, and 4 in the classification scheme of airway
obstruction will only respond to a nasopharyngeal airway or tracheotomy, if
this fails. The nasopharyngeal airway
may be left in place for up to 8 weeks when used as definitive therapy. While
the tube is in place, gavage feeding through an orogastric tube is recommended.
Hearing:
Otitis media with effusion is common in these
patients, due to eustachian tube dysfunction from the palatal anomalies.
Treacher Collins Syndrome
(Mandibulofacial dysostosis)
Treacher Collins Syndrome occurs in approximately 1 in 25,000 to 1 in
50,000 live births. Inheritance is
autosomal dominant with variable expressivity.
The syndrome is characterized by bilateral, symmetric abnormalities of
first and second branchial arch structures.
The disorder is characterized by hypoplasia of the maxilla, zygoma and
mandible with a prominent nasal dorsum, giving them a convex facial
profile. The eyes have a downward
slant, and the lower eyelids typically have colobomas and an absence of
eyelashes. The auricles are malformed
or absent with varying degrees of middle ear cavity hypoplasia and ossicular
malformation. Cleft palate, cleft lip,
and choanal atresia may also be present.
Airway:
Respiration may be compromised by maxillary
hypoplasia with choanal stenosis or atresia and by micrognathia and a
retropositioned tongue. Airway
management can be especially difficult in these patients, especially when the
need for intubation or laryngoscopy arises.
Careful coordination with a pediatric anesthesiologist is usually necessary. Obstructive sleep patterns may develop,
which may respond to tonsillectomy or mandibular osteotomy procedures, during
craniofacial reconstruction.
Hearing:
There is often a bilateral conductive hearing loss
of 50 to 70 dB resulting from varying degrees of middle ear cavity hypoplasia
and ossicular malformations. Early
formal audiology testing is indicated.
The inner ear structures are usually normal, however, successful
surgical correction can be extremely difficult or dangerous. If the chance for a successful
reconstruction is poor (based on temporal bone scans), rehabilitation with
hearing aids is necessary.
Apert and Crouzon Syndromes
Apert syndrome
(acrocephalosyndactyly) was credited by Apert’s description in 1906. Six years later, Crouzon described a mother
and daughter, who had the same malformation of the face and head, coining the
term hereditary craniofacial dysostosis.
Both are characterized by craniosynostosis, hypertelorism, exopthalmos,
maxillary hypoplasia, and mandibular prognathism. Apert syndrome has the added feature of syndactyly. Inheritance of each is autosomal dominant,
and the prevalence is similar, between 15 and 16 per 1 million births.
Airway:
Because of the cranial synostosis, the maxillary
height, nasal cavity width, bony nasopharyngeal height, and the nasopharyngeal
airway are all reduced. These
malformations lead to severe compromise of the nasopharyngeal and oropharyngeal
spaces, which pose a serious risk of impaired respiratory function, obstructive
sleep apnea, cor pulmonale and sudden death.
Treatment of respiratory distress is endotracheal intubation, followed
by tracheotomy if the problem persists.
Sleep apnea evaluation includes a sleep study, and if obstructive may
require tracheotomy if severe. Central
apnea can be caused by increased intracranial hypertension, and requires
cranial vault decompression. Forced
mouth breathing in these children often causes feeding problems, which require
nasogastric or gastrostomy feedings.
Cervical spine anomalies (mostly vertebral fusions, C5-6) may occur, so
cervical spine radiographs should be obtained prior to procedures requiring
general endotracheal anesthesia.
Hearing:
Hearing loss is usually acquired from eustachian
tube dysfunction, probably as a result of midface hypoplasia and decreased
nasopharyngeal space. Treatment often
requires the placement of ventilation tubes.
Goldenhar Syndrome
(Oculoauriculovertebral spectrum)
Goldenhar syndrome is a unilateral craniofacial malformation
characterized by facial asymmetry, unilateral external and middle ear
deformities, and vertebral malformations.
Most cases are sporadic, however autosomal dominant and recessive cases
have been reported. The incidence is 1
in 5600 live births. Some believe that
a vascular anomaly during fetal life causes hemorrhage into the 1st
and 2nd branchial arches, thus producing the subsequent
malformations. Other findings include
upper eyelid colobomas and facial weakness (in 10 to 20%). These patients can present a challenging
airway for surgical procedures, however, most of the concern is with
hearing. Hearing loss is present
greater than 50% of the time and is usually conductive, due to ossicular
malformations or absences and external auditory canal atresia. Sensorineural loss is present occasionally.
C.H.A.R.G.E. Association
CHARGE is the association of 4 or more of the following anomalies: coloboma, heart defects (tetralogy of
Fallot, ASD, VSD, PDA), atretic choanae, retardation of growth, genitourinary
anomalies, and ear malformations. The
most pressing otolaryngologic concern is with choanal atresia which is
bilateral frequently. The neonate
begins to have immediate respiratory distress, which should be relieved with an
oral airway promptly. Other options
include a McGovern nipple or intubation, if these fail. Repair may be delayed because of more
serious anomalies associated with this condition, and if so, tracheotomy can be
performed. The ear malformations may
include any combination of the external, middle and/or inner ear. Deafness is usually of the mixed type with a
characteristic "wedge"-shaped audiogram.
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