CRANIOFACIALMALFORMATIONS

DR HASIKA BHIMALA

FINAL YEAR

M.S.OPHTHALMOLOGY

CRANIOSYNOSTOSIS

Craniosynostosis is the premature closure of 1 or more cranial sutures during the embryonic period or early childhood.

Cranial sutures are present throughout the skull, which is divided into 2 parts, the calvarium and the skull base, via an imaginary line drawn from the supraorbitalrims to the base of the occiput.

A, Normal sutures and fontanelles of the fetal skull.

8, Adult cranial base, complete with sutures

Bony growth of the skull occurs in osteoblastic centers located at the suture sites.

Bone is laid down parallel and perpendicular to the direction of the suture.

Premature suture closure prevents perpendicular growth but allows parallel growth.

This pattern is termed Virchow's law and leads to clinically recognizable cranial bone deformations, all of which carry specific nomenclature.

The following are important terms associated with craniosynostosis, in order of frequency of occurrence.

A, Normal sutures. Bone growth occurs at the suture, laid down parallel and

perpendicular to the direction of the suture. B, Virchow's law. Prematurely fused

sutures allow bone growth only in the parallel direction; perpendicular growth is

inhibited. C, An example of Virchow's law. Closure of the sagittal suture

produces scaphocephaly (boatlike skull) when compared to the normal skull

(shaded area).

PLAGIOCEPHALY

The term plagiocephaly literally means "oblique head.“

Most often it is the consequence of a unilateral coronal suture synostosis.

On the synostotic side, the forehead and supraorbitalrim are retruded (depressed), the interpalpebral fissure is wider, and the orbit is often higher than on the non synostotic side.

Because of brain growth and necessary cranial vault expansion, the non synostotic side will display protrusion or bulging of the forehead, lower supraorbital rim, narrower interpalpebral fissure, and often a lower orbital position.

A, Fused coronal suture, with inhibition of perpendicular skull growth. B, Patient

with left coronal synostosis. Note retruded left forehead, elevated brow, and

wider interpalpebral fissure, with compensatory protrusion of the right forehead,

lower brow, and narrowed interpalpebral fissure.

Oxy-, turri-, acrocephaly

These terms all mean "tower head." The condition occurs most often with multiple suture closures, such as both coronals, the sagittal, and possibly the lambdoidals.

Brachycephaly "Short head";

specifically refers to growth in the anterior-posterior axis. Brachycephaly is often the result of bilateral closure of the coronal sutures. The forehead is most often wide and flat.

Scaphocephaly "Boat head.”

Scaphocephaly usually results from premature closure of the sagittal suture; the skull is thus long in the anterior-posterior axis and narrow bitemporally.

Dolichocephaly "Long head";

the skull shape is much like that in scaphocephaly.

Kleeblattschiidel "Cloverleaf skull";

the skull shape is trilobar. Kleeblattschadel is typically the result of synostosis of the coronal, lambdoidal, and sagittal sutures.

result of synostosis of the coronal, lambdoidal, and sagittal sutures.

Hypertelorism, orbital

Excessive distance between the medial orbital walls. This diagnosis is made not clinically but rather radiographically.

Hypertelorism. ocular

Excessive interpupillary distance when compared to standard nomograms; it implies orbital hypertelorism.

Telecanthus Increased distance between the medial canthi. This may be secondary to hypertelorism, but it can be a primary soft tissue abnormality.

CALVARIAL SUTURE FUSION AFFECTS CRANIAL SHAPE AND ORBITAL DEVELOPMENT.

SKULL BASE SUTURE FUSION AFFECTS FACIAL AND ORBITAL DEVELOPMENT.

In contrast to calvarial suture fusion, which causes different cranial deformations, skull base suture fusion causes just 1 constellation of abnormalities, midface hypoplasia, specifically consisting of the following :

Maxillary hypoplasia

Beak-shaped nose

Hypertelorism

Shallow orbits with proptosis and lagophthalmos

High-arched palate with dental malocclusion

Relative mandibular prognathism (prominent-appearing jaw is due to retruded maxilla)

Note the manifestations of skull base suture fusion-namely, severe

midface retrusion, shallow orbits, proptosis. beak-shaped nose-in this

child with Crouzon syndrome

Not all skull deformities are secondary to synostosisof a suture.

Deformational plagiocephaly is a skull deformation secondary to intrauterine constraint (eg, oligohydramnios) and is characterized by ipsilateraloccipital flattening with contralateral forehead flattening.

The skull takes on a trapezoidal shape when viewed from above.

The ear is displaced anteriorly on the side of the flattened occiput.

ETIOLOGY OF CRANIOSYNOSTOSIS

Early suture fusion can occur sporadically as an isolated abnormality (eg, sagittal suture synostosisand most cases of unilateral coronal suture synostosis), or it can be associated with other abnormalities and part of a genetic syndrome.

Craniosynostosis syndromes are usually autosomaldominant conditions, and many of these syndromes have associated limb abnormalities.

The most frequent craniosynostosis syndromes are Apert, Crouzon, Pfeiffer, and Saethre-Chotzen.

Many of the craniosynostosis syndromes have overlapping features, making accurate diagnosis based on clinical findings difficult.

Advances in gene discovery have revealed that many of these syndromes are caused by mutations in the fibroblast growth factor receptor (FGFR) genes 1,2, and 3 and the TWIST gene.

These mutations result in increased calvarial cell differentiation and bone matrix formation.

Mutations are found in approximately 50% of craniosynostosis syndrome patients.

CRANIOSYNOSTOSIS SYNDROMES

Common systemic features of the craniosynostosissyndromes include fusion of multiple calvarialsutures and skull base sutures.

Syndactyly and brachydactyly, ranging in severity, are also hallmarks of these syndromes - with one notable exception, Crouzon syndrome.

CROUZON SYNDROME

Crouzon syndrome is the most common autosomaldominant craniosynostosis syndrome.

Over 30 mutations cause the Crouzon phenotype, all occurring on the FGFR2 gene on chromosome 10.

Calvarial bone synostosis often includes both coronal sutures, resulting in a broad, retruded forehead; brachycephaly; and tower skull.

The skull base sutures are also involved, leading to varying degrees of midface retrusion.

There is often marked variability of the skull and facial features, with milder cases escaping diagnosis through multiple generations.

Hypertelorism and proptosis, with inferior scleral show (lower eyelid below limbus with scleral baring), are the most frequent features of Crouzon syndrome.

Intelligence is usually normal.

Findings are usually limited to the head.

There are no obvious hand or foot abnormalities, such as those encountered in Apert and other craniosynostosis syndromes, which can greatly aid the clinician in the diagnosis of Crouzon.

Hydrocephalus is common.

Crouzon syndrome. This patient evidences turribrachycephaly with forehead retrusion, proptosis, inferior scleral show, and a small, beaklike nose. Also visible is the emerging midface hypoplasia.

APERT SYNDROME

Patients with Apert syndrome usually have multiple fused calvarial sutures, most often both coronal sutures, and skull base suture fusion.

Although the skull shape and facial features of these patients may resemble those of patients with Crouzonsyndrome, the former display an often extreme amount of syndactyly, causing all the digits (hands and feet) to be completely fused.

Apert syndrome is likely to be associated with internal organ malformations (cardiovascular and genitourinary) and mental deficiency.

Hydrocephalus is less common. The condition is autosomal dominant.

Two mutations, both on the FGFR2 gene on chromosome 10, account for most patients who carry this diagnosis.

Patient with Apert syndrome. A. Note turribrachycephaly, forehead and superior orbital rim retrusion, maxillary hypoplasia, beaklike nose with depression of nasal bridge, and trapezoid-shaped mouth (common in infancy in Apert syndrome). B, Extreme syndactyly of the digits; the thumb is spared but is broad and deviated. When all digits are fused, it is termed mitten deformity. C. Syndactyly of the toes analogous to that of the hands.

Patients with Pfeiffer syndrome have craniofacial abnormalities similar to those of Apert syndrome patients, often with more severe craniosynostosis, resulting in a cloverleaf skull.

In Pfeiffer syndrome, the syndactyly is much less severe, and patients have characteristic short, broad thumbs and toes.

This syndrome is autosomal dominant and secondary to mutations on FGFR genes I or 2.

SAETHRE-CHOTZEN SYNDROME

In general, the features of Saethre-Chotzensyndrome are much milder than those of other craniosynostosis syndromes; this syndrome is therefore often underdiagnosed.

Early suture fusion is not a constant feature but, when present, typically involves 1 coronal suture (plagiocephaly), inducing an asymmetric face, a characteristic cited as a classic feature of Saethre-Chotzen syndrome.

Other common features are ptosis, low hairline, and ear abnormalities.

The hands and feet display slightly shortened digits (brachydactyly) and mild syndactyly.

Intelligence is usually normal.

The condition is autosomal dominant.

Mutations in the TWIST gene on chromosome 7 cause the Saethre-Chotzen phenotype.

Patient with Saethre-Chotzen syndrome. Note the facial asymmetry, flat forehead,

low-set hairline, mild left ptosis. classic lateral deviation of the great toes,

shortened toes, and partial syndactyly of fingers 2 and 3.

OCULAR COMPLICATIONS

PROPTOSIS

Proptosis (or exorbitism) in craniosynostosis results from the reduced volume of the bony orbit that usually occurs in syndromes with coronal and/or skull base suture fusion.

The severity of the proptosis in these patients is not uniform and frequently increases with age because of the impaired growth of the bony orbit.

CORNEAL EXPOSURE

Because the eyelids may not close completely over the proptotic globes, corneal exposure may occur secondary to inadequate blink and/or nocturnal lagophthalmos, with possible development of exposure keratitis.

Exposure keratitis, in the short term, leads to punctateepithelial erosions, epithelial defects, and possible infectious keratitis.

If exposure keratitis is not prevented or treated, scarring of the cornea will ensue and result in vision loss.

Aggressive lubrication is necessary to prevent corneal drying.

Tarsorraphies can decrease the exposure.

Surgically expanding the orbital volume, thereby eliminating the proptosis, is the treatment when the proptosis and exposure are severe and lubrication and tarsorraphies fail.

GLOBE LUXATION

Patients with extremely shallow orbits may suffer globe luxation when their eyelids are manipulated or when there is increased pressure in the orbits, such as occurs with a Valsalva maneuver.

The globe is luxated forward, with the eyelids closing behind the equator of the globe.

The condition is very painful and can cause corneal exposure; it may also possibly compromise the blood supply to the globe, which is a medical emergency.

Physicians and patients (or their caregivers) should quickly replace the globe behind the eyelids.

The best technique for doing this is to place a finger and thumb over the conjunctiva within the interpalpebral fissure and exert gentle but firm pressure to reposition the globe; this technique does not damage the cornea.

For recurrent luxation, the short-term solution is tarsorraphy; the long-term solution is orbital volume expansion.

Vision Loss

Patients with craniofacial syndromes commonly suffer vision loss owing to a variety of causes: corneal scarring from exposure, uncorrected refractive errors, amblyopia, and optic nerve compromise.

Most cases of vision loss can be prevented.

Amblyopia

Amblyopia is common in patients with craniofacial syndromes and is secondary to high uncorrected refractive errors, anisometropia, and strabismus, all of which occur more frequently in these patients.

Strabismus

Patients with craniosynostosis show a variety of horizontal deviations in primary position; exotropia is the most frequent.

The most consistent finding, however, is a marked V pattern.

This V pattern is often accompanied by a marked apparent overaction (pseudooveraction) of the inferior oblique muscles, especially when 1 or both coronal sutures are synostosed, as occurs in unicoronalsynostosis and Apert and Crouzon syndromes.

Patient with Apert syndrome, Note the good alignment in primary

position with marked elevation of adducted eyes (inferior oblique

overaction) and exotropia in upgaze (V pattern).

Optic Nerve Abnormalities

Because the synostosed cranial vault is unable to expand as the brain grows, the intracranial contents become crowded, elevating intracranial pressure (ICP).

Papilledema can occur because of elevated ICP, and chronic papilledema can eventually lead to optic atrophy and vision loss.

Hydrocephalus is another cause of elevated ICP and occurs in up to 40% of patients with Apert, Crouzon, and especially Pfeiffer syndromes.

The severe midface retrusion that these conditions produce may cause breathing problems and sleep apnea.

Idiopathic intracranial hypertension secondary to sleep apnea can also cause elevated ICP and papilledema.

Optic atrophy may also occur with or without antecedent papilledema.

Children with elevated lCP may not complain of a headache.

Therefore, young patients with multiple fused sutures should be examined yearly or biyearly.

Optic nerve edema and/or atrophy can also occur secondary to optic nerve foramina synostosis, where the bony canal stenoses.

This is rare but has been described in patients with craniofacial syndromes.

Ocular Adnexa Abnormalities

Patients with craniosynostosis syndromes display more adnexal abnormalities than do patients with isolated suture fusion.

Common abnormalities include orbital hypertelorism, telecanthus, abnormal slant of the palpebral fissures secondary to superior displacement of the medial canthi, ptosis, and nasolacrimal apparatus abnormalities such as duct obstruction and punctal anomalies.

Epiphora is a common finding in these patients and may be secondary to nasolacrimalapparatus abnormalities that produce obstruction; poor blink secondary to proptosis; obliquity of the palpebral fissures; or ocular irritation from corneal exposure.

MANAGEMENT

In recent decades, there have been major advances in reconstructive surgery for severe craniofacial malformation.

This surgery is frequently extensive and involves en bloc movement of the facial structures.

The status of the visual system should be documented preoperatively, with attention to vision, the eyelids and orbit, and the motility examination.

Postoperatively, the function of the visual system should be reevaluated and appropriate treatment instituted.

In many centers, a specialized craniofacial team-comprising facial plastic surgeons, neurosurgeons, ophthalmologists, and oral surgeons-collaborates to determine the timing of the reconstructive surgery by prioritizing the child's multiple problems.

Common surgical procedures include frontoorbitaladvancement; Le Fort II, or midface advancement; orbital hypertelorism repair; and a variety of jaw procedures.

The first 2 procedures involve manipulation of the orbits and expansion of orbital volume.

In addition, reconstructive surgery that involves moving the orbits may significantly change the degree or type of strabismus, thereby modifying the indicated form of strabismus surgery.

Another consideration is that improved binocular function may not be attainable in these patients because of their unusual and incomitant form of ocular muscle imbalance.

Thus early strabismus surgery may offer no particular advantage, and deferring treatment until craniofacial surgery is completed may be appropriate.

NONSYNOSTOTIC CRANIOFACIAL

CONDITIONS

Many craniofacial syndromes do not involve synostosis.

A few of particular importance to the ophthalmologist are discussed in the following sections.

BRANCHIAL ARCH SYNDROMES

Branchial arch syndromes are caused by disruptions in the embryonic development of the first 2 branchialarches, which are responsible for the formation of the maxillary and mandibular bones, the ear, and facial musculature.

The best known of these syndromes are oculoauriculovertebral (OAV) spectrum, which includes hemifacial microsomia and Goldenharsyndrome, and Treacher Collins syndrome.

OCULOAURICULOVERTEBRAL

SPECTRUM

There has been no firm agreement about the nomenclature involved with this condition, but most believe that hemifacial microsomia (HFM) is the formefruste of the OAV spectrum.

Hemifacial microsomia affects aural, oral, and mandibulargrowth.

Patients with HFM may display, on the involved side, decreased jaw and cheek growth, ear abnormalities such as microtia or anotia (small or absent external ear), pretragal skin tags, deafness, and facial weakness (cranial nerve VII courses through the middle ear).

Macrostomia can also occur. Hemifacial microsomia is usually unilateral but may be bilateral.

Patients with the OAV spectrum may have characteristic vertebral abnormalities such as hemivertebrae and vertebral hypoplasia.

They may also have neurologic, cardiovascular, and genitourinary abnormalities. Most cases are sporadic, but there are rare familial cases.

GOLDENHAR SYNDROME

Goldenhar syndrome is a more severe presentation of the OAV spectrum.

Patients with Goldenhar syndrome have HFM (unilateral or bilateral) in addition to characteristic ophthalmic abnormalities. Most cases are sporadic.

Epibulbar and limbal dermoids are the ocular hallmarks of Goldenhar syndrome.

Epibulbar dermoids (also termed lipodermoids) usually occur in the inferotemporal quadrant, covered by conjunctiva and often hidden by the lateral upper and lower eyelids.

Limbal dermoids are reported more frequently than lipodermoids and can be bilateral (in approximately 25% of cases).

They occasionally impinge on the visual axis but more commonly interfere with visual acuity by causing astigmatism; they can also cause anisometropicamblyopia.

Hemifacial microsomia, Goldenhar variant. Patient has facial asymmetry, a hypoplastic left ear (microtia), an ear tag near the right ear, limballipodermoid in the left eye, and esotropia. Patient also has a left Duane syndrome.

Eyelid colobomas may occur.

Other abnormalities include microphthalmia, cataract, and iris abnormalities . Duane syndrome is more common in patients with Goldenhar syndrome than in the general population.

TREACHER COLLINS SYNDROME

Abnormal growth and development of the first and second branchial arch in Treacher Collins syndrome (mandibulofacial dysostosis) give rise to underdevelopment and even agenesis of the zygomaand malar eminences bilaterally.

The cheeks and lateral orbital rims are depressed and the palpebral fissures slant downward because of lateral canthal dystopia.

Pseudocolobomas (and, uncommonly, true colobomas) are found in the outer third of the lower eyelids.

Meibomian glands may be absent.

The cilia of the lower eyelid may be absent, medial to the pseudocoloboma.

The ears are malformed and hearing loss is common.

The mandible is typically hypoplastic, leading to micrognathia.

Macrostomia is common.

Intelligence is normal.

The syndrome is inherited in an autosomal dominant fashion and displays variable expression.

Most patients with this syndrome have a mutation in the TCOF 1 gene.

Mandibulofacial dysostosis (or Treacher Collins syndrome). Note downward slant of palpebral fissure, low-set abnormal ears, notch or curving of the inferotemporal eyelid margin, and maxillary and mandibular hypoplasia.

PIERRE ROBIN SEQUENCE

The Pierre Robin sequence (also anomaly, deformity) is characterized by respiratory problems, micrognathia, glossoptosis, and cleft palate.

These abnormalities occur in a variety of syndromes, and the Pierre Robin sequence is a frequent finding in Stickler syndrome.

Associated ocular anomalies include retinal detachment, microphthalmos, congenital glaucoma, cataracts, and high myopia.

FETAL ALCOHOL SYNDROME

Fetal alcohol syndrome is an example of a craniofacial condition caused by in utero exposure to a teratogen, in this case ethanol.

Alcohol and other teratogens can produce a wide range of effects on the developing fetus, depending on consumption or dose, timing of intake, genetic background, and other factors.

A pattern of malformations has been observed in children born to women with a history of heavy alcohol use during pregnancy.

Fetal alcohol syndrome, the term applied to this pattern, is characterized by prenatal and postnatal growth retardation, central nervous system abnormalities, and a wide spectrum of malformations, the most typical of these being craniofacial.

Other facial features include a thin vermilion border of the upper lip. Mental retardation, ranging from mild to severe, occurs often in children with this syndrome.

Fetal alcohol syndrome. Asymmetric ptosis; telecanthus; strabismus; long, flat philtrum; anteverted nostrils. This child also had Peters anomaly of the left cornea and myopia of the right eye,

The classic ocular characteristics of fetal alcohol syndrome are short palpebral fissues, telecanthus, epicanthus, ptosis, microphthalmos and strabismus, namely esotropia.

Anterior segment dysgenesis, optic nerve hypoplasia, and high refractive errors have also been reported.

Half of children with this syndrome, which is underdiagnosed, will suffer some form of visual impairment.