Chapter 35: Craniofacial Syndromes

8. Can you name the six functional units that drive craniofacial development?

1. Central neurologic system 2. Optic pathway 3. Speech and swallowing development 4. Airway and pharyngeal development 5. Muscles of facial expression development 6. Tooth development and exfoliation

22. What are the physical and radiographic signs of craniosynostosis?

Absence of the affected suture with an irregular ridge of bone in its place. Abnormal cranial and orbital morphology, depending upon the affected suture(s). Elevated ICP may demonstrate as a scalloped "copper beaten" appearance or thinning and erosion of the inner surface of the skull on CT.

27. What is the most important perioperative consideration for patients undergoing correction of craniosynostosis?

Acute blood loss. Careful attention must be given to volume status. The majority of patients undergoing open treatment require a blood transfusion

6. What is the functional matrix theory of craniofacial growth?

Anatomist Melvin Moss proposed the concept in the 1960s that development of the facial skeleton was directly related to the mechanics and functions of the various units that comprise the facial skeleton. Modern day interpretation has included an intrinsic (genetic) pattern that is altered by extrinsic (epigenetic) factors.

31. What is Apert syndrome?

Apert syndrome is a form of craniofacial dysostosis that is characterized by bilateral coronal craniosynostosis with a widely patent midline calvarial defect, orbital hypertelorism, ptosis of the upper eyelids and downward slanting lateral canthi, midface hypoplasia, beaked nose, cleft palate (30%), hearing loss (30%), developmental delay, complex syndactaly of fingers and toes, and thick facial skin with increased sebaceous discharge. Macrocephaly and other CNS malformations may be present. Apert syndrome is thought to be associated with advanced paternal age.

9. At what age is the majority of orbital/zygomatic growth completed?

Approximately 85% of orbitozygomatic growth is completed between 5 and 7 years of age.

33. What are the other most common named craniofacial syndromes?

Carpenter, Saethre-Chotzen, Beare-Stevenson, Jackson-Weiss, and Meunke.

38. What are the surgical options for correction of orbital hypertelorism?

Circumferential orbital osteotomies can be completed through a combined intracranial/extracranial approach. The orbits can be translocated after excision of a portion of the intervening interorbital tissues (frontal and nasal bones, floor of the anterior cranial fossa, ethmoid air cells, and nasal septum). Patients who have severe constriction of the maxilla can be managed with a facial bipartition procedure.

41. Can you describe the cloverleaf skull deformity?

Cloverleaf skull, also known as kleeblattschädel, refers to the trilobar skull shape characterized by multiple suture craniosynostosis, towering and bossing of the forehead, flattening of the posterior skull, and expansion or bulging of the temporal regions. The etiology is heterogeneous, and cloverleaf skull anomalies are often seen in conjunction with a spectrum of brain malformations. It can occur in the absence of craniosynostosis

39. What adjunctive procedures are often necessary at the time of orbital hypertelorism correction?

Concurrent dorsal nasal augmentation and medial canthopexies

17. What is craniosynostosis?

Craniosynostosis is the premature fusion of one or more sutures of the cranial vault. It leads to an arrest of growth along the affected suture(s) that results in compensatory growth at the unaffected sutures leading to characteristic dysmorphology. In general, it occurs as an intrauterine event.

30. What is Crouzon syndrome?

Crouzon syndrome is a form of craniofacial dysostosis that is characterized by bilateral coronal craniosynostosis; other sutures are less often involved. This results in a brachycephalic skull with anterior retrusion, midface hypoplasia and exorbitism. Conductive hearing loss is a common finding. Patients demonstrate a typical IQ.

10. What is meant by deformational plagiocephaly?

Deformational plagiocephaly is a nonsynostotic cranial deformity due to external forces. Most commonly, this presents with asymmetric occipital flattening and anterior displacement of the ipsilateral ear and forehead. Severe cases commonly occur in conjunction with torticollis. It is necessary to differentiate between deformational plagiocephaly and lambdoid craniosynostosis, which presents with ridging of the affected suture, severe flattening of the affected occipitoparietal region, ipsilateral retrusion of the forehead, and superior-posterior displacement of the ear

20. Can you describe the consequences of craniosynostosis?

Depending upon the number and type of suture(s) that are involved, craniosynostosis can lead to abnormal morphology of the cranium, orbits, and face. In addition, it is thought to be associated with increased intracranial pressure (ICP). In the classic study by Marchac and Renier, approximately 14% of children with untreated single craniosynostosis demonstrated increased ICP. The percentage increased to 42% when two or more sutures were fused. Causality between craniosynostosis and elevated ICP is still debated in the literature. Finally, involvement of the coronal suture and ring may result in shortening of the orbit, decreased volume, strabismus, ptosis, abnormal binocular vision, and exorbitism.

21. What are the clinical findings that may be reported in children with untreated craniosynostosis who develop increased ICP?

Headaches, vomiting, sleep disturbance, behavioral changes, and diminished cognitive function have all been reported. Prolonged elevated ICP will produce papilledema, optic nerve atrophy, and eventual vision loss. Signs of elevated ICP in association with single suture craniosynostosis are not usually encountered before 1 year of life.

19. What is Virchow's law?

In 1851, Rudolf Virchow described the cessation of growth perpendicular to a fused cranial suture, with compensatory growth occurring at the remaining sutures in a parallel direction. In 1989, Delashaw further expanded this concept with four additional observations to predict the patterns of abnormal cranial morphology in more detail.

12. How is deformational plagiocephaly treated?

In mild cases, observed prone positioning and counterpositioning of the head will support normalization of symmetry over time. In severe cases, families may elect to proceed with the use of a custom molding helmet that is generally worn between the ages of 7 and 14 months of age.

35. What is the general sequence of surgical treatment of patients with craniofacial dysostosis syndromes?

In patients demonstrating increased ICP, early suturectomy and cranial vault expansion are performed. Otherwise, craniectomy and anterior cranial vault reconstruction with fronto-orbital advancement are completed before 12 months of age. Repeat craniofacial expansion may be required during childhood if findings of increased ICP are noted. Residual forehead retrusion, orbital hypertelorism, and midface deficiency can be managed after orbitozygomatic development is largely complete (5 to 7 years of age) by monobloc, facial bipartition, or Le Fort III procedures as indicated by the individual deformity. Final malocclusion is treated with more traditional orthognathic surgical techniques at skeletal maturity

34. What is the genetic basis for Saethre-Chotzen syndrome?

Mutation in the TWIST 1 gene and subsequent TWIST 1 protein. A small subset of patients have a chromosomal abnormality in the region of chromosome 7 that contains the TWIST 1 gene.

32. What is Pfeiffer syndrome?

Pfeiffer syndrome is a form of craniofacial dysostosis that has 3 clinical subtypes with variable penetrance. In general, Pfeiffer syndrome is characterized by craniosynostosis, orbital dystopia, midface hypoplasia, broad and deviated thumbs and toes, and variable syndactyly of the hands and feet. Type 1 is considered the classic form as described above, and patients have a good prognosis. Type 2 is the most severe in presentation and includes the cloverleaf skull deformity, significant neurologic deficit, and a limited lifespan. Type 3 is similar in severity but does not include the cloverleaf skull deformity. There are a number of other low-frequency limb and organ abnormalities that may occur.

7. How do remodeling and displacement contribute to craniofacial skeletal harmony?

Remodeling occurs as a result of local factors that lead to a change in the size and shape of the facial skeleton. Displacement occurs by the movement of bones away from each other at a suture or articulating surface (e.g., cranial sutures, temporomandibular joints, maxillary sutures). If the processes of remodeling and displacement do not occur in a balanced fashion, a skeletal discrepancy will occur.

23. Can you describe the most common forms of nonsyndromic craniosynostosis?

SUTURE/ SHAPE/ PREVALENCE /COMMENTS Sagittal /Scaphocephaly/ 1:5000 /Elongated (length) Narrow (width) Coronal(unilateral)/ Plagiocephaly (anterior)/ 1:10,000/ Shortened orbit, retruded forehead, harlequin eye, contralateral bossing, deviation of the nasal root toward the affected side Coronal (bilateral)/ Brachycephaly (anterior)/ Rare/ Syndromic Exorbitism Metopic /Trigonocephaly/ 1:15,000/ Hypotelorism, low incidence of elevated ICP, often associated with other malformations and/or delay Lambdoid (unilateral)/ Plagiocephaly (posterior)/ 1:150,000/ Commonly confused with deformational plagiocephaly Lambdoid (bilateral)/ Brachycephaly (posterior)/ Rare/ Syndromic

2. Can you describe the rate of growth of the brain cranial vault of a child?

The brain is thought to grow in propulsive fashion. Over the first two years of life, the volume of the brain and cranium increase fourfold. Head circumference has reached 86% of its final size by age 1 and 94% by age 5. The maturation age of cranium width is 14 years in females and 15 years in males.

3. How does the skull form and develop?

The cranial vault is formed by intramembraneous ossification, and bone deposition continues at the sutures. Endocranial resorption and ectocranial deposition continue in step with brain growth and expansion of the overlying soft tissue envelope. The three distinct layers of the skull do not develop until 3 to 5 years of life

36. What are the most common craniofacial conditions that include orbital hypertelorism?

The craniofacial dysostosis syndromes, (cranio) frontonasal dysplasia, and midline facial clefts.

1. What are the components of the craniofacial skeleton?

The craniofacial skeleton is composed of the neurocranium (cranial vault and cranial base) and the viscerocranium (facial skeleton). The bones of the cranial vault are derived from the paraxial mesoderm and are formed through intramembranous ossification; the formation and expansion of ossification centers are directly within mesenchymal tissue. The bones of the cranial base are formed through endochondral ossification.

40. What is the position of the cribriform plate in patients with orbital hypertelorism, and why is this important?

The cribriform plate is often inferiorly positioned with prolapse of the frontal lobes. Retraction and elevation are critical for the safe medial translocation of the orbits.

18. An abnormality in what anatomic structure is thought to lead to craniosynostosis?

The dura.

26. When should surgical treatment of craniosynostosis take place, and what are the two approaches that are used?

The exact timing depends upon the type of treatment, but surgery generally takes place before 12 months of age. Endoscopic treatment is undertaken at an earlier age, around 3 months of life. It consists of multiple small incisions, suturectomy, and often multiple wedge craniectomies. The use of a postoperative cranial molding helmet is mandatory. Open treatment is undertaken between 6 and 12 months of life. It consists of a coronal incision, craniectomy, fronto-orbital advancement as indicated, and cranial vault reconstruction. If multiple sutures are involved or the need for treatment is urgent, early surgery may be undertaken with a plan for additional reconstruction.

4. What embryologic structures lead to the development of the face?

The frontonasal prominence and first pharyngeal arch. At weeks 4 to 5 the stomedial depression is surrounded by primordial structures that develop into facial structures: the frontonasal prominence, paired nasomedial and nasolateral prominences, and paired maxillary and mandibular prominences. The maxillary and mandibular prominences are derived from the first pharyngeal arch with Meckel's cartilage acting as an ossification template for the mandible.

28. What is the most common location of the genetic mutation found in craniofacial dysostosis syndromes, and how are they transmitted?

The genetic abnormality is most commonly found on the fibroblast growth factor receptor (FGFR) genes 1, 2, and 3. The most common are the FGFR2-related dysostosis syndromes. They are generally inherited in an autosomal dominant pattern.

24. What is the harlequin eye deformity?

The harlequin eye deformity is the radiographic appearance of the superior lateral position of the ipsilateral orbit and wing of the sphenoid seen in unilateral coronal craniosynostosis.

25. At what age does the metopic suture physiologically fuse?

The metopic suture has been shown to fuse as early as 3 months of life. When this occurs, there is commonly a nonsynostotic ridge that forms. This can make the diagnosis of metopic craniosynostosis challenging in mild cases.

37. What are the key features of frontonasal dysplasia?

The most common presentation includes anterior cranium bifidum, orbital hypertelorism, a widow's peak, wide nasal dorsum with a bifid tip, and a midline cleft of the lip and palate. Craniofrontonasal dysplasia is likely a subtype that is inherited in an X-linked dominant pattern and more commonly seen in females. It has similar features, but includes craniosynostosis (most commonly bilateral coronal), thick and wiry hair, and other low-frequency extremity abnormalities.

16. How many fontanelles are present in the developing skull?

There are four fontanelles: anterior, posterior, lateral/sphenoid (bilateral), and mastoid (bilateral)

15. How many sutures are present in the cranial vault?

There are four major cranial vault sutures: metopic, coronal (bilateral), sagittal, and lambdoid (bilateral). There are multiple other minor sutures

13. Is there a relationship between deformational plagiocephaly and developmental delay?

This is a controversial topic that is actively being investigated. A causal relationship has yet to be demonstrated.

11. Why has the incidence of deformational plagiocephaly increased since 1992?

This is the year that the American Association of Pediatrics (AAP) introduced the "back to sleep" campaign to decrease sudden infant death syndrome (SIDS)

14. What is torticollis?

Torticollis is an abnormal twisting of the head and neck. In children, this is most commonly caused by shortening or contracture of the sternocleidomastoid muscle. Congenital muscular torticollis is present at birth and may be due to intrauterine positioning, birth trauma, neurologic injury/disorder, or tumor, or it may be idiopathic. Acquired torticollis is thought to be a result of supine positioning with prolonged rotation of the head and neck. The clinical appearance is characterized by a rotation and tilting of the head toward the affected side with the chin pointing in the contralateral and superior direction. There may be a fibrotic mass depending upon the etiology. Treatment involves physical therapy, observed prone positioning, and counter positioning of the head. In rare instances, Botox injections or surgical lengthening of the SCM may be required. Delay in treatment or refractory cases may lead to facial and cranial asymmetry and may require management with a cranial orthotic

42. What are the characteristic features of Binder syndrome?

Variable nasomaxillary hypoplasia that may affect the frontal sinus, nose, upper lip, anterior septum, floor of the nose, and premaxillary-derived tissues. Clinical presentation includes midface deficiency, absence of anterior nasal spine, short nose with limited projection, acute nasolabial angle, and a flat nasofrontal angle. The nostrils appear crescent or semilunar in shape when viewed from below

29. What are the general functional considerations in patients with craniofacial dysostosis syndromes?

• Craniosynostosis may restrict brain growth and be associated with elevated ICP leading to cognitive and behavioral delays as well as optic nerve compression. • Untreated optic nerve compression will initially cause papilledema and eventually result in optic nerve atrophy and blindness. • Shallow orbits result in proptosis of the globe that may lead to corneal desiccation/ulcers as well as globe herniation in severe cases. Dystopia and strabismus are also common orbital findings. • Hydrocephalus is a concern and is postulated to be secondary to constriction of the cranial base foramina and diminished venous drainage. • Severe midface hypoplasia may contribute to airway obstruction and sleep apnea. Early evaluation with polysomnogram may be indicated. • Dental crowding, eruptive abnormalities, and malocclusion are common.

5. What are the differences among malformation, disruption, and deformation?

• Malformation: The abnormal formation of tissue as a result of an intrinsic developmental defect. In general, the later the defect occurs in gestation, the less extensive the malformation (e.g., spinal bifida). • Disruption: This is the breakdown of previously developed tissue causing abnormal morphology due to pressure resulting in amputation or vascular compromise (e.g., amniotic band). • Deformation: This is changes in morphology caused by external mechanical forces on normal tissue (e.g., oligohydramnios, intrauterine constraint, or abnormal fetal presentation).