Treacher Collins Syndrome
What is Treacher Collins Syndrome?
Treacher Collins Syndrome, also called mandibulofacial dysostosis, affects the head and
face. Characteristics include:
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down-slanting eyes
notched lower eyelids
underdevelopment or absence of cheekbones and the side wall and floor of the eye
socket
lower jaw is often small and slanting
forward fair in the sideburn area
underdeveloped, malformed and/or prominent ears
Most children with Treacher Collins have normal development and intelligence; however,
it is important that there be early hearing tests. Most children with Treacher Collins
Syndrome benefit from early intervention speech and language programs.
Why did this happen?
Treacher Collins Syndrome is believed to be caused by a change in the gene on
chromosome 5, which affects facial development. About 40 percent of the time, one parent
has the Treacher Collins Syndrome gene. Geneticists can now determine whether the
Treacher Collins gene is a new mutation or one that has been passed on.
Will this happen to children I have in the future?
Treacher Collins Syndrome may be inherited from a parent affected with Treacher Collins.
There is a 50% change of passing it on if you have it. If may also occur in children of
unaffected parents. However, the chances of Treacher Collins occurring again in children
of unaffected parents is minute.
What kinds of problems could my child have?
In addition to the physical characteristics common to Treacher Collins syndrome, your
child may have some or all of the following problems:
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breathing problems and/or eating difficulties
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most children have a 40% hearing loss in each ear due to abnormalities of the outer
and middle ear, which conduct sound to the nerve endings
the eyes have a tendency to dry out, which can lead to infection
some children have abnormally small or absent thumbs
cleft palate often occurs with Treacher Collins Syndrome
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Will my child need surgery?
Depending on the severity of the Treacher Collins, your child may need some or all of the
following procedures:
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a conductive hearing aid
correction of the cleft palate
repair of the sidewall and floor of the eye socket
repair of the cheekbones
repair of the eyelid notches
correction of the undeveloped jaw and chin
surgery to correct the beak-like nose
reconstruction of the ears
New advances in the procedures to treat Treacher Collins Syndrome are constantly being
developed. Be an advocate for your child!
How do I get help for my child?
Your child should be treated by a qualified craniofacial medical team at a craniofacial
center. Currently, FACES has information on thirty-two craniofacial teams located in 20
states, the District of Columbia, and Canada. This is by no means a comprehensive list of
all the craniofacial teams. Please contact FACES for details on possible locations closer to
you.
Klippel-Feil Syndrome
In 1912, Maurice Klippel and Andre Feil were independently the first to describe
Klippel-Feil syndrome. They described patients who had a short neck, increased range of
motion (ROM) in the cervical spine, and a low hairline. Feil subsequently classified the
syndrome into 3 categories. Type I is described as a massive fusion of the cervical spine.
Type II is present when the fusion of 1 or 2 vertebrae occurs. Type III occurs when
thoracic and lumbar spine anomalies are associated with type I or type II Klippel-Feil
syndrome.
Patients with Klippel-Feil syndrome usually present during childhood but may present later
in life. The challenge to the clinician is to recognize the associated anomalies that can
occur with Klippel-Feil syndrome and to perform the appropriate workup for diagnosis.
Frequency: The true incidence of Klippel-Feil syndrome is unknown. No one has ever
studied a cross-section of healthy people to determine the true incidence.
The incidence of Klippel-Feil syndrome has been investigated in 2 studies, using 2
different means. Gjorup reviewed all of the radiographic cervical spine films in a single
hospital in Copenhagen. From these radiographs, he determined an incidence of 0.2 cases
per 1000 people. Brown reviewed 1400 skeletons from the Terry collection at Washington
University School of Medicine. He found an incidence of 0.71%.
Etiology: The etiology of Klippel-Feil syndrome and its associated conditions is unknown.
The syndrome can present with a variety of other clinical syndromes, including fetal
alcohol syndrome, Goldenhar syndrome, and other anomalies in the extremities.
Gunderson suggested that it is a genetic condition, while Gray found a low incidence of
inheritance. Others have considered it to be some type of global fetal insult, which could
explain the other associated conditions. Others have considered it to be caused by vascular
disruption. The true etiology has yet to be determined.
Clinical: Clinical presentation is varied because of all of the associated syndromes and
anomalies that can occur in patients with Klippel-Feil syndrome. A complete history and
careful physical examination may reveal some associated anomalies. From an orthopedic
standpoint, most of the workup is with imaging (see Imaging Studies).
The condition is detected throughout life, often as an incidental finding. Patients with
upper cervical spine involvement tend to present at an earlier age than those whose
involvement is lower in the cervical spine. Most patients present with a short neck,
decreased cervical ROM, and a low hairline, which occurs in 40-50% of patients.
Decreased ROM is the most frequent clinical finding. Rotational loss usually is more
pronounced than is the loss of flexion and extension.
Other patients present because of cosmesis or facial asymmetry. Neurological problems
may develop in 20% of patients. Pouliken found that 5 of 19 patients with Klippel-Feil
syndrome had neurological involvement; of these 5 patients, 2 had neurological problems
due to hypermobility at one level. Occipitocervical abnormalities were the most common
cause of neurological problems (see Images 1-4). Some patients present with pain.
Hensinger and colleagues described the constellation of anomalies that can occur with
Klippel-Feil syndrome, and others have added to this list. Scoliosis occurs in
approximately 60% of patients (see Images 5-6). In some patients, this is congenital
scoliosis (see Image 7) due to the involvement of other parts of the thoracic or lumbar
spine. Other patients develop compensatory scoliosis in the thoracic spine to compensate
for the cervical or cervicothoracic scoliosis. In addition to the fusion anomalies in the
cervical spine, cervical spinal stenosis can occur. While uncommon, this can increase the
risk of neurological involvement.
Anomalies of the craniocervical junction can cause instability at lower segments.
Traumatic tetraplegia has been reported following minor trauma. A Sprengel anomaly
occurs in 20-30% of patients (see Image 7). Always check ROM of the shoulders. Look for
an omovertebral bone (see Image 8). This is an osteocartilaginous connection that tethers
the scapula to the spine. An omovertebral bone ossifies with age, further limiting the ROM.
A CT scan best demonstrates an omovertebral bone; however, palpation or radiographs
also can detect an omovertebral bone. Other upper extremity anomalies occur less
frequently. A thorough examination of the ROM and function of the upper extremity must
be performed.
Synkinesia is mirror movement of the upper extremity. Patients with this condition are
unable to perform a movement of the right hand without performing the same movement of
the left hand (see Image 9). This is disabling in activities of daily living (ADL). Synkinesia
often may be improved with therapy and usually improves with age.
Renal anomalies are common in individuals with Klippel-Feil syndrome, and they can be
quite serious. Hensinger reviewed 50 patients, and 41 of them had an intravenous
pyelogram (IVP). Renal anomalies were present in 16 (34%). Minor renal anomalies were
detected in 6 individuals, including a double collecting system, renal ectopia, and bilateral
tubular ectasia. Major renal anomalies were detected in 10 individuals, including
hydronephrosis, absence of a kidney (see Image 10), and a horseshoe kidney. As Hensinger
notes, the patient of Klippel and Feil died of renal failure and uremia. Patients with
Klippel-Feil syndrome now have ultrasound as the initial test to demonstrate the presence
of 2 functioning kidneys.
Torticollis and facial asymmetry occur in 21-50% of patients with Klippel-Feil syndrome.
These patients also may have a muscular torticollis. Craniofacial anomalies also can occur.
Hearing loss is common with Klippel-Feil syndrome. The hearing loss can be sensorineural,
conductive (one third of cases), or mixed. Hensinger found the incidence of hearing loss to
be 36%. Early audiometric evaluation and otologic evaluation are indicated in all children
when the diagnosis of Klippel-Feil syndrome is established.
Cardiovascular anomalies occur in 14-29% of cases. The most common cardiovascular
defect is an interventricular septal defect. Other less common anomalies are congenital
limb deficiencies, craniosynostosis, ear abnormalities, iniencephaly, and craniofacial
abnormalities.
Patients with Klippel-Feil syndrome present at different ages with varying
clinical presentations. Indications for the complexity of the workup vary
individually. For the orthopedic surgeon, the most usual indications for surgery
depend upon the amount of deformity, its location, and its progression with
time. Other indications include instability of the cervical spine and/or
neurological problems. These indications can occur with craniocervical
junction anomalies and also when 2 fused segments are separated by a
normal segment.
Some patients present early in life with complex cervical and cervicothoracic
deformity that is progressive and disfiguring. Some of these patients require
cervical spine fusions to prevent progression.
Other patients may develop compensatory or associated congenital scoliosis,
which also can be progressive over time and requires fusion to prevent
progressive deformity. Over one half of the patients in Hensinger's study had
scoliosis. Treatment of the scoliosis with bracing or surgery was required in 18
of the 50 patients.
Contraindications: Since this is a syndrome with a constellation of possible abnormalities,
no set of definite contraindications exists. If a surgeon believes that an operation is
indicated, it is incumbent upon him/her to make certain none of the other conditions that
could cause morbidity or mortality are present. Cervical or occipitocervical instability
could cause increased risk during intubation. An underlying heart defect could increase
anesthetic risk. An increased risk of neurologic damage during spinal fusion for correction
of deformity could result from underlying spinal stenosis or spinal cord abnormality. A
thorough workup of the patient is imperative prior to surgical intervention. Imaging
Studies:
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Plain radiography is the basis for the diagnosis of Klippel-Feil
syndrome.
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Initial studies include anteroposterior (AP) and lateral views of
the cervical spine.
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If anomalies are found, carefully assess the craniocervical
junction to detect anomalies at that level.
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Flexion-extension radiographs are indicated if instability is
suspected at the craniocervical junction or if 2 fused segments
are separated by an open segment.
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Obtain plain radiographs of the entire spine to detect other spinal
anomalies.
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Examine the chest to rule out involvement of the heart. Examine
the chest wall for the possibility of rib anomalies, which can
include multiple rib fusions. Rib fusions can be revealed with
plain radiography.
CT scan often is more useful at the spinal level.
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For patients being evaluated for surgery, CT scan with
3-dimensional reconstruction can be a very valuable tool to
assess the anatomy.
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A unilateral unsegmented bar or cervical stenosis may be
revealed on a CT scan, which helps the physician plan the
surgical procedure.
MRI
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MRI is indicated in patients with neurological deficits.
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Flexion-extension MRI may reveal cord compression and is
useful in evaluating spinal stenosis.
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In patients with neurological deficits, obtain an MRI of the entire
spine to search for central nervous system anomalies, such as a
syringomyelia.
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Ultrasound initially is performed to visualize the kidneys.
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Perform intravenous pyelography if any kidney abnormality is
suspected with ultrasound.
Other Tests:
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Due to the high incidence of hearing loss with Klippel-Feil syndrome, an
audiologist or an otologist should evaluate all children
Medical therapy: Medical therapy is dependent upon the congenital
anomalies present in the syndrome. Primary care physicians may not be
familiar with all of the possible associated anomalies. Patients with
genitourinary abnormalities are referred to a nephrologist or urologist. Patients
with cardiovascular abnormalities are cared for by a cardiologist or primary
care physician. Patients with auditory abnormalities are referred to an
audiologist or otologist.
Surgical therapy: Surgery is indicated for a variety of situations in patients
with Klippel-Feil syndrome. Due to fusion anomalies and the difference in
growth potential between the 2 sides of the spine, deformity may be
progressive. Instability of the cervical spine can develop because of
craniocervical abnormalities. Instability of the cervical spine also can develop
between 2 sets of fusion anomalies separated by normal segment. Neurologic
deficits or persistent pain are indications for surgery. Development of a
compensatory curve in the thoracic spine may require surgical intervention or
bracing. Symptomatic spinal stenosis may require decompression and fusion.
Koop and colleagues studied 13 cases of children who were skeletally
immature with a variety of disorders that caused instability of the upper part of
the cervical spine from the occiput to C5. These researchers were looking at
the efficacy of posterior arthrodesis and halo-cast mobilization. Many of these
patients did not have Klippel-Feil syndrome, but the surgical indications were
instability. Posterior arthrodesis with external mobilization by halo-cast was
carried out. In 2 of the patients, internal fixation with wire was utilized. A solid
arthrodesis was obtained in 12 patients treated with autogenous bone graft.
One patient treated with allograft rib developed a pseudoarthrosis.
Koop et al cautioned that the use of wires for fixation carries risk of neural
injury and often is not applicable in children with anomalous vertebra. They
stress the need for delicate exposure, decortication using an air drill, and
placement of autologous iliac graft. They recommended mobilization by
halo-cast, which they thought would minimize the risk of neural damage and
provide a reliable means of obtaining arthrodesis.
Preoperative details: Patients must have a comprehensive workup to detect
the anomalies previously mentioned. Adequate imaging studies must be
obtained. Three-dimensional CT scan reconstruction often is useful.
Crouzon syndrome
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craniofacial dysostosis
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autosomal dominant
premature closure of sutures(craniosynostosis)
o usually coronal ==> brachycephaly
o all sutures ==> Kleeblatschaedel
hypoplasia of facial bones
beaked ("parrot") nose
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A Guide to Understanding Apert Syndrome from the Children's Craniofacial Association
highly recommended reading!
What is Apert Syndrome?
The following was developed from information contained in an article entitled Clinical Assessment and
Multispecialty Management of Apert Syndrome, written by Lawrence C. Kaplan, MD, and published in
Clinics in Plastic Surgery-Vol. 18, No. 2, April 1991.
Major Features of Apert Syndrome
Prematurely fused cranial sutures
A retruded midface
Fused fingers
Fused toes
Possible Related Features of Apert Syndrome
These have been observed in some cases of Apert syndrome, although whether they were caused by Apert
syndrome is uncertain.
Various heart defects
Dextrorotation
Pulmonary Atresia
Patent Ductus Arteriosus (PDA)
Tracheoesophageal Fistula
Pyloric stenosis
Polycystic kidneys
Bicornate uterus
Hydrocephalus
Ear infections
Sleep Apnea
Severe acne
Increased incidence of eye injuries
Definition
Apert Syndrome is a genetic defect and falls under the broad classification of craniofacial/limb anomalies. It
can be inherited from a parent who has Apert, or may be a fresh mutation. It occurs in approximately 1 per
160,000 to 200,000 live births. Apert syndrome is primarily characterized by specific malformations of the
skull, midface, hands, and feet. The skull is prematurely fused and unable to grow normally; the midface
(that area of the face from the middle of the eye socket to the upper jaw) appears retruded or sunken; and
the fingers and toes are fused together in varying degrees. Apert syndrome is named for the French
physician who first described it, E. Apert, in 1906.
In a normal child, the skull is made up of several "plates" which remain loosely connected to one another,
gradually growing together to form the adult skull. The Apert child's skull, by contrast, has a premature
fusion of these plates, restricting brain growth, and causing increased pressure in the brain as it grows. This
is known as craniosynostosis. Early surgery relieves the pressures by allowing the plates to be detached
from one another. During this early surgery some "cranial remodeling" may be done to give the child a more
normal appearance.
The "retrusion" or hypoplasia of the midface is what could be described as a concave or dished in profile. As
the skull grows, the upper and lower thirds of the face tend to grow at normal rates, but the middle third of
the face grows slower, resulting in a more pronounced retrusion over time. A surgical procedure known as
the LeFort III is used to correct this condition. The procedure is usually done after substantial growth is
complete (preadolescence) and may be repeated as necessary. The LeFort procedure involves detaching
the facial bones from mid eye to upper jaw and spacing this area out with bone grafts so that a proper
alignment is made. In the last few years, some surgeons have come to prefer the Rigid External Distraction
(RED) system or internally placed distractors, instead of or in conjunction with, traditional craniofacial
surgery.
The fusion of the fingers and toes along with the craniofacial problems mentioned above is what really
separates Apert from other similar syndromes. This condition is called syndactyly. It always involves fusion
of the soft tissues of the first, middle, and ring fingers, and often there is fusion of the bones themselves.
Joint mobility is usually nonexistent past the first joint. The thumb may be fused into the hand, or may be
free. Surgery is used to separate the fingers to obtain the highest degree of functionality, and may or may
not ultimately result in five digits on each hand. It varies according to the degree of malformation. The feet
and toes are affected similarly, but surgery is usually only recommended in cases where the ability to walk
would be impaired.
Ideally, treatment of Apert begins at birth with the proper diagnosis, identification of the child's individual
needs, and the proper facilities to administer what is needed. A multidisciplinary approach is used by
physicians in the best arrangements. A craniofacial anomalies team may consist of a craniofacial surgeon,
neurosurgeon, ENT, audiologist, speech pathologist, oral surgeon, psychologist, ophthalmologist, and an
orthodontist. The team approach is used by these physicians to determine the best collaborative corrective
plan for the deficiencies of the child.
Genetics
Apert syndrome is a result of genetic mutation. When you have Apert syndrome, you have a 1 in 2 (50%)
chance of passing this condition to your child. This is because each of us gets 1/2 of our genetic makeup
from each parent. However, Apert is not a recessive trait, which means that the UNaffected child of a parent
with Apert syndrome is no more likely to have a child with Apert than any other person; also, if you have a
child with Apert and you do NOT have Apert, YOU are no more likely to have another child with Apert than
anyone else in the population. Studies have shown that Apert occurs more often in children of older fathers.
Recently studies were conducted at Oxford University and they managed to identify the actual genetic
change which occurs in Apert. The following is a quote from a letter sent to the test families by Oxford.
"A total of 86 children and adults affected with Apert syndrome have been seen. From the blood samples
which have been donated for research, we have identified the genetic change that causes the condition. The
change is in a gene on chromosome number 10 called 'Fibroblast Growth Factor Receptor 2' (FGFR2 for
short). We all have two copies of this gene (one from mother, one from father), which is composed of a
string of about 2000 of the chemical building blocks that make up the genetic material called DNA. When
Apert syndrome occurs, just one particular building block in one of these two gene copies has been
exchanged for another. The other gene copy is entirely normal. This one tiny change in the FGFR2 gene
results in the physical features of Apert syndrome."
CHARGE ASSOCIATION/SYNDROME
1.
Definition
2.
Epidemiology
3.
Etiology
4.
Clinical Manifestations
5.
Treatment
6.
Prognosis
7.
Reference Page
Definition:
CHARGE association (or syndrome) is an acronym referring to children
with a specific pattern of birth defects. The acronym is: "C" for coloboma,
"H" for heart defects, "A" for atresia choanae, "R" for retardation of growth
and development, "G" for genitourinary problems, and "E" for ear
abnormalities.19
Epidemiology:
The incidence of CHARGE is about 1 out of 10,000-12,000 births. It
affects males and females of all races equally.20
Etiology:
Etiology is unknown, but it has been suggested that deficiency in migration
of neural crest cells, deficiency of mesodermal formation, or defective
interaction between neural crest cells and mesoderm play a part in these
defects of blastogenesis.21 Some findings suggest that a gene or genes
causing some of the anomalies of CHARGE association may reside in the
region 14q22-q24.3. All malformation occur in the first trimester.
Clinical Manifestations:
Traditionally, CHARGE association includes:
Coloboma is cleft or failure of the eyeball to close resulting in
abnormalities of the retina or optic nerve. This may result in significant
loss of vision, defects in visual acuity resulting in near or farsightedness,
and oversensitivity to light.
Heart defects include Tetralogy of Fallot, the most frequent type of heart
defect reported in the CHARGE association. The tetralogy is "an anatomic
abnormality with severe or total right ventricular outflow tract obstruction
and a ventricular septal defect allowing right ventricular unoxygenated
blood to bypass the pulmonary arteries and enter the aorta directly.17(p2059)
Atresia choanae is the blocking (atresia)of the airways (choanae) from the
back of the nose to the throat that would allow breathing through the nose.
Retardation of growth and development is usually due to heart problems,
nutritional
problems, or growth hormone deficiency. The developmental delay often is
associated with sensory deficits (vision and hearing loss). Some children
with CHARGE will be mentally retarded.
Genitourinary problems, in boys includes genital hyposplasia and possibly
undescended testes. The girls may have small labia. Reflux of the urinary
tract or kidneys is common.
Ear abnormalities include a common finding of unusually shaped ears (short
and wide with very little or no earlobe). Hearing loss, conductive and/or
nerve, ranges from mild to deafness.
Recent literature has supported the classification of CHARGE as a syndrome.
They define major criteria specific to CHARGE as the four C's: coloboma
(80-90%); choanal atresia (50-60%); characteristic ear abnormalities (90%), and
cranial nerve dysfunction (70-90%). Cranial nerve dysfunctions include: CN I
(anosmia); CN VII (facial palsy); CN IX/X (swallowing problems, reflux, and
drooling); CN VIII (sensorineural hearing loss). Minor criterion, which are less
specific to CHARGE, includes genital hypoplasia (70-80%), developmental
delay (100%), orofacial cleft (15-20%), distinct facial patterns (70-80%), and
altered palmar creases (50%).
22
Diagnosis:
At least four of these abnormalities should be present if a child is to be
diagnosed as having CHARGE Association. In any child suspected to have
CHARGE, cardiorespiratory, ophthalmological, and audiological evaluations
may be performed as well as abdominal ultrasound and chromosome evaluation.
Treatment:
Many of the structural anomalies can be surgically corrected. Due to
developmental delay most children with CHARGE will not be mobile until
20-25 months and will not ambulate independently until 35-57 months making
early intervention crucial. Many will demonstrate a "five-point" crawl with
their head down dragging on the floor. Because of the developmental delay,
early intervention would play an important role in mobility, improving static
postures, transitioning towards ambulation, and teaching self care skills.
22
Prognosis:
Choanal atresia is life-threatening because young infants cannot establish the
habit of breathing through their mouths. Prognosis is based on the severity of
factors. For example, a severe case with major developmental delay and growth
retardation has a poor prognosis while one with surgically correctable
malformations may lead a happy, healthy life.
Goldenhar Syndrome
Goldenhar syndrome is variant of Hemifacial Microsomia. It's
severity can vary and the effects can be unilateral or bilateral. The
physical manifestations of this disorder match those of Hemifacial
Microsomia with the addition of epibulbar dermoids which are
benign tumors located just inside the opening of the eye or the
eyeballs.
Characteristics:
The physical characteristics of Goldenhar syndrome include:
Unilateral or Bilateral underdevelopment of the Mandible
Unilateral or Bilateral Microtia
Unilateral or Bilateral reduction in size and flattening of the Maxilla (upper jaw)
Narrowing of the opening of the eye
Epibulbar Dermoids which can cause problems with vision.
The lack of growth and facial asymmetry of Hemifacial Microsomia are accompanied by
epibulbar dermoids.
Causes:
The origin of this syndrome is thought to be a vascular accident in the fetus. This accident
causes the blood supply to be cut off and production of blood clots in the area of those
tissues which will develop into the structures of the ear and lower jaw. The amount of
damage caused by the vascular accident is directly related to the period of development in
which it occurs as well as the degree of tissue destruction that takes place. Since it is not
genetically linked, most cases of Goldenhar syndrome are sporadic and the risk of an
effected individual to have an affected child is minimal.
Expectations:
Due to the delayed growth and development of the effected areas, the effects of this
syndrome will be more evident as the child grows. The lack of the development of the upper
and lower jaws can cause breathing problems as well as a dental malocclusion which will
need to be addressed surgically and orthodontically.
Treatment:
For these patients, treatment generally requires the expertise of both a craniofacial surgeon
and an orthodontist with experience with these problems. The jaw deformity is addressed as
early as 3 years of age if the mandibular retrusion is severe enough to cause airway
difficulty. This jaw reconstruction can be achieved by extending the mandible with a rib
graft or with the utilization of a distraction device to "stretch" the bone. The best approach to
reconstructing the jaw is determined by the surgeon and is specific for each patient. If it is
needed, ear reconstruction is performed in four stages and usually begin at the age of six
years. Throughout life, these patients must maintain adequate dental occlusion through
ongoing orthodontic treatment.