Pediatric craniofacial surgery for craniosynostosis: Our experience and current concepts: Parts -2.

Craniostenosis associated with other syndromes poses several clinical and management challenges. Involvement of cranial, facial, and systemic defects with an underlying genetic abnormality needs comprehensive understanding, to plan appropriate and safe treatment modalities. Often, these children require staging involving several/multiple surgical procedures. Unsuccessful outcomes and retrusion of the deformities are common in comparison to the nonsyndromic variety. We present our experience in treating 17 children with syndromic craniostenosis with successful outcomes and minimal morbidity. We also describe the principles behind the staging. Technology adoption has improved the results as well as reduced the complications to an acceptable minimum.

Introduction

Craniosynostosis can involve any of the skull sutures in isolation or in combination. In simple craniosynostosis, one suture is prematurely fused. In multiple-suture synostosis, two or more sutures are prematurely fused. Craniosynostosis can occur in isolation or in conjunction with other anomalies, in well-defined patterns that make up as clinically recognizable syndromes. Most of the isolated nonsyndromic craniosynostosis occur sporadically, whereas syndromic craniosynostosis is most often genetic in nature, autosomal dominant or recessive, and with X-linked inheritance. More than 90 series reported that syndromes are associated with craniosynostosis, some involving associated anomalies of the limbs, ears, and the cardiovascular system.

The Apert, Crouzon, Pfeiffer, Saethre-Chotzen, and Carpenter syndromes represent more commonly identified craniosynostosis syndromes. These familial craniosynostosis syndromes share many common features, including midface hypoplasia, cranial base growth abnormalities, abnormal facies, and limb abnormalities. In fact, the craniofacial features are clinically similar among many syndromes, such that the digital anomalies of the hands may be the sole differentiating feature between them. Although it is clear that synostosis of the cranial sutures is significantly responsible for the development of abnormal craniofacial features in these syndromic children, there could be an associated mesenchymal defect in the cranial base that also contributes to the craniofacial deformity [Figures 1–5].

Figure 1

Complex craniostenosis with midline cleft

Figure 5

Ventricular enlargement with septal malformation

3_D of craniofacial anomaly

3-d showing skull vault defect and midface hypoplasia

Parenchymal abnormality

The exact etiology of craniosynostosis in these syndromic children remains unclear. Advances in molecular genetics provide insights into a possible link between mutations identified in fibroblast growth factor receptor (FGFR) genes and several autosomal dominant skeletal disorders. Fibroblast growth factors participate in the regulation of cell proliferation, differentiation, and migration, and play a major role in controlling normal bone morphogenesis via complex cell-signaling pathways. The transduction of a fibroblast growth factor signal to the cytoplasm is mediated by a group of transmembrane tyrosine kinase receptors known as FGFRs. Mutations in three of the four known FGFR genes located on chromosomes 8, 10q, and 4p have been identified in the Pfeiffer, Apert, Crouzon, and Jackson-Weiss syndromes. Achondroplasia, a skeletal disorder that causes the most common form of short-limb dwarfism, is also linked to a mutation in the FGFR complex. The Pfeiffer syndrome is linked to a mutation in both the FGFR1 and FGFR2 genes, whereas, the Crouzon and the Apert syndromes are linked to the mutations in the FGFR2 complex.[12]

Specific Syndromes

Crouzon Syndrome (Acrocephalosyndactyly Type II)

The Crouzon syndrome is characterized by the premature fusion of calvarial sutures, midface hypoplasia, shallow orbits, and ocular proptosis. The clinical features were first described by Crouzon, a French neurologist, in 1912. The pattern of inheritance is autosomal dominant. The reported frequency is 1 in 25,000 live births. The variability in expression of the dominant features that make up the Crouzon syndrome is widely recognized [Figure 6].

Figure 6

Crouzon syndrome

Premature fusion of both coronal sutures, resulting in a brachycephalic head, is the most common calvarial deformity, but scaphocephaly and trigonocephaly, as well as cloverleaf skull deformity, have been observed. Craniosynostosis is often complete by 2–3 years of age, but occasionally the sutures are fused at birth. The cranial base sutures are frequently involved, resulting in maxillary or midface hypoplasia. The maxillary hypoplasia is evidenced by a reduced dental arch width and a constricted high palatal arch. Normal mandibular growth leads to class III malocclusion.

Midface hypoplasia is reflected in the shallow orbits with exorbitism, which is a consistent finding and can result in exposure conjunctivitis or keratitis. Exorbitism can be so severe that herniation of the globe through the eyelids may occur, requiring immediate reduction of visual acuity defects, and strabismus and hypertelorism can be associated. A conductive hearing deficit is not uncommon. There are no commonly reported anomalies of the digits in this group.

Apert Syndrome (Acrocephalosyndactyly Type I)

Apert, in 1906, described a syndrome characterized by craniosynostosis, exorbitism, midface hypoplasia, and symmetric syndactyly of both hands and feet. The incidence is reported to be 1 in 160,000 live births. Most often they are sporadic, although several cases with autosomal dominant transmission have been reported. The cranial vault deformity in these children is variable, but most often presents as a short anteroposterior dimension with craniosynostosis involving the coronal sutures resulting in a turribrachycephalic skull. The typical craniofacial appearance includes a flat, elongated forehead with bitemporal widening and occipital flattening. Midface hypoplasia is accompanied by orbital proptosis, downslanting palpebral fissures, and hypertelorism. The nose is downturned at the tip, the bridge is depressed, and the septum deviated [Figures 7 and 8].

Figure 7

Apert's syndrome

Figure 8A

Syndactyly

Maxillary hypoplasia results in a class III malocclusion. Hand syndactyly, which is pathognomic for the condition, most often involves fusion of the second, third, and fourth fingers, resulting in a mid-digital hand mass, but the first and fifth fingers may also be joined to the mid-digital mass. When the thumb is free, it is broad and deviates radially. In the feet, the syndactyly usually involves the second, third, and fourth toes. These hand anomalies are so severe and functionally debilitating that referral to an experienced hand surgeon is essential.

An extensive review of central nervous system (CNS) problems in patients with Apert syndrome shows an increased incidence of delayed mental development, although a majority exhibit normal intelligence.

Pfeiffer Syndrome (Acrocephalosyndactyly Type V)

This syndrome was described by Pfeiffer in 1964, and consists of craniosynostosis, broad thumbs, broad great toes, and occasionally a partial syndactyly involving the second and third digits. Symptoms vary, ranging from very mild to severe. The mode of inheritance is autosomal dominant.

The craniofacial features are similar to those of the Apert syndrome. The skull is turribrachycephalic secondary to the coronal and occasional sagittal synostosis. Maxillary hypoplasia with resulting midface deficiency leads to shallow orbits and exorbitism. Hypertelorism and downslanting palpebral fissures are also common. The nose is often downturned with a low nasal bridge. Intelligence is reported to be normal in the more common form of Pfeiffer syndrome. Broad thumbs and great toes are the hallmarks of the syndrome, but the findings are frequently subtle. The partial syndactyly of the hands usually involves digits 2 and 3. A partial syndactyly of toes 2, 3, and 4 has also been noted.

Saethre-Chotzen Syndrome (Acrocephalosyndactyly Type III)

This syndrome was first described by Saethre in 1931 and by Chotzen in 1932. The predominant features include a brachycephalic skull, a low-set frontal hairline, and facial asymmetry with ptosis of the eyelids. The mode of inheritance is autosomal dominant with a wide variability in expression.

The craniofacial features, which involve a brachycephalic skull, are secondary to bicoronal synostosis. The low-set hairline is also a constant feature of this syndrome. The facial asymmetry is often accompanied by deviation of the nasal septum and maxillary hypoplasia, with a narrow palate. Intelligence is usually normal. A partial syndactyly involving the second and third digits is often observed, and short stature is also a frequent finding.

Carpenter Syndrome

This is a rare genetic disorder characterized by craniosynostosis of various sutures, leading to an asymmetric head, partial syndactyly of the digits, and preaxial polysyndactyly of the feet. The syndrome was first described by Carpenter in 1901, but not recognized as a significant clinical syndrome until 1966, when it was reported by Temtamy. The mode of transmission is autosomal recessive.

The craniofacial features are variable and significantly influenced by the shape of the skull. As craniosynostosis can involve the lambdoid, sagittal, and coronal sutures, the head shape may vary from brachycephalic to turricephalic. Low-set ears and lateral displacement of the inner canthi are prominent features. Mental deficiency has been reported, and congenital heart defects have been reported in as many as 33% of the children. Soft-tissue syndactyly of the hands usually involves the third and fourth digits.

Pathogenesis

To fully appreciate the surgical treatment of children with these craniosynostosis syndromes, it is necessary to understand the craniofacial growth process and its relation to the functional aspects of development. Normal craniofacial growth is directed by two general processes: displacement and bone remodeling. During the first year of life, the brain triples in size and continues to grow rapidly up to about 6 or 7 years of age. The growth of the brain causes displacement of the overlying frontal, parietal, and occipital bones in the presence of open functioning sutures, and this stimulates bone growth and remodeling in the skull and cranial fossa. The growth and maturation of the face follows a craniocaudal gradient, progressing from late childhood to adolescence, with maturation of the upper face followed by the midface and finally the mandible. In the following sections, the functional aspects of development, which are directly or indirectly influenced by abnormal craniofacial growth, are examined individually.

Intracranial Pressure

The size of the brain triples in the first year and continues to grow rapidly up to the age of 6 to 7 years. In a child with craniosynostosis, there can be restricted growth of the cranial vault, resulting in a disparity between brain size and intracranial volume, leading to increased intracranial pressure (ICP.

ICP can be recognized clinically by funduscopic examination as papilloedema, and in later stages as “thumb printing” or the beaten-silver appearance on plain radiographs. Unfortunately, there is no reliable indicator of increased ICP. In a study that evaluated ICP with an epidural sensor in 358 children with various types of craniosynostosis, it was found that children with multiple suture synostosis had higher rates of increased ICP (26–54%). In the syndromic population, increased ICP was noted in 66% with Crouzon syndrome and 43% with Apert syndrome. However, it has been documented by 3-D CT scan that an increase in intracranial and ventricular volume can occur following cranial vault reshaping, causing ICP. Nevertheless, a CT scan alone cannot accurately predict changes in ICP.

Visual Changes

Craniosynostosis can result in abnormal growth of the skull, often accompanied by midface hypoplasia. Underdeveloped shallow orbits or abnormally shaped orbits can cause the eyes and periorbital structures to be displaced from their normal position; this is termed as “exorbitism.” Exorbitism can result in corneal exposure and the development of keratitis, pain, infection, corneal scarring, and at worst, ulceration and blindness. Occasionally, the degree of exorbitism is so great that immediate surgical intervention is required to protect the globe. These are significantly more in the syndromic variety.

Ocular motility problems frequently arise secondary to the abnormal size and shape of the orbits. Strabismus with exotropia is a common finding. Abnormal development and position of ocular muscles have also been frequently reported in children with Crouzon or Apert syndrome. Increased ICP leading to papilledema and optic atrophy can result in blindness. Whether the optic atrophy is secondary to increased ICP or due to damage to the nerve from compression or a compromised vascular supply is not entirely clear.

Hydrocephalus

Although the incidence of hydrocephalus and craniosynostosis is rare, various incidence of hydrocephalus is significantly higher, ranging from 4% to 10%. There is clearly a higher incidence of hydrocephalus among children with Apert syndrome. The etiology of hydrocephalus remains unclear, but it has been postulated to be due to increased venous pressure in the sagittal sinus, secondary to obstruction of the venous outflow caused by the craniosynostosis. Both communicating and noncommunicating forms of hydrocephalus have been reported, but the communicating form is more common.

Hydrocephalus can present without either marked head enlargement (which may be difficult to detect in patients with syndromic craniosynostosis) or signs of increased ICP. Preoperative CT scanning or ultrasonography may help define the population at risk. At the earliest sign of progressive ventricular enlargement, a shunting procedure should be performed to prevent cerebral insult.

Materials and Methods

Seventeen children – 13 males and 3 females – with associated syndromes were operated in stages for craniofacial anomalies. 1(male) Pancraniostenosis. Six children had crouzon's syndrome and 10 had Apert's syndrome. Apert's syndrome seems to affect the male children more. One child had pancraniostenosis involving multiple sutures. They were operated in stages after detailed clinical and radiological evaluations. The first stage involved cranial vault correction with orbital advancements. In the second stage, midface corrections were planned. The staged procedures registered successful results, with good tolerance of the procedure. Detailed study of parenchyma and psychological evaluation was important to counsel the parents about the outcome. There was no mortality in our series. Transient CSF leak was managed conservatively.

Surgical Management

The surgical treatment of patients with craniosynostosis syndromes dates back to the late nineteenth century, when the first techniques were aimed at correcting only the functional aspects of the deformity. The earliest techniques were linear craniectomy and fragmentation of the cranial vault, which are still useful in some of the severe variety to provide temporary brain and eye protection, until a definitive procedure is planned. Simple craniectomy or morcellization performed in infancy is unfortunately accompanied by a high rate of reossification, and will give only modest results when mobilization of the orbits and midface is not performed concurrently. Additionally, the reossified bone is of poor quality, making definitive correction more difficult later on.

In 1967, Tessier first published his results following correction of the recessed forehead and supraorbital regions using an intracranial approach that allowed accurate osteotomy, mobilization, and repositioning. The current surgical approach for children with syndromic craniosynostosis and accompanying midface deficiency involves initial fronto-orbital and cranial vault remodeling, a midface advancement procedure with or without distraction (Le Fort III or monobloc), and secondary orthognathic surgery to correct any dentofacial deformities (Le Fort I, mandibular osteotomies).

Surgical intervention for the correction of craniofacial deformities in patients with syndromic craniosynostosis can be divided into those procedures that are performed early in life (4–12 months) for suture release, cranial vault decompression, and upper orbital reshaping/advancement, and those that are performed at a later age (4–12 years) for midface deformities and jaw surgery (14–18 years). The exact timing and sequence for each of the aforementioned surgical procedures will depend on both the functional and psychological needs [Table 1].

Table 1

Syndromic craniosynostosis treatment options

The major controversy is centered around the timing of midface osteotomies. Two approaches are currently practiced: (a) waiting until all midface and lower face growth are complete before doing a definitive osteotomy and advancement, or (b) performing a midface advancement in childhood with the realization that a second advancement will be necessary when mandibular growth is complete. Midface advancement is usually performed using distraction techniques, the complications of blood loss and infection have been reduced significantly, making the procedure more acceptable in childhood.

Fronto-orbital Advancement

The surgical goal of fronto-orbital advancement is threefold: (a) to release the synostosed suture and decompress the cranial vault, (b) to reshape the cranial vault and advance the frontal bone, and (c) to advance the retruded supraorbital bar, providing improved globe protection and an improved esthetic appearance. The procedure is performed through a coronal incision. With the assistance of a neurosurgical team, a frontal craniotomy is performed to release the synostosed suture and elevate the frontal bone. In certain instances, the child may have previously undergone a prior frontal craniotomy by the neurosurgical staff to release the coronal suture, when elevated ICP was suspected. Reossification would have usually occurred by 1 year of age. Once the frontal bone is removed, the brain is gently retracted, exposing the underlying retruded supraorbital bar, which is advanced in a tongue-in-groove manner and secured with miniplates. Cranial vault remodeling is dependent on the preoperative head shape. For severe turricephaly, a total cranial vault reshaping is performed; this procedure allows for a significant reduction in the vertical height of the skull. For a child with mild turricephaly, only the anterior two-thirds of the vault is remodeled. The supraorbital bar and forehead are advanced into an overcorrected position to allow room for further brain growth.

Following this initial fronto-orbital advancement and cranial vault remodeling procedure, the child is followed up once in 6–12 months by the craniofacial team. Continued growth of the cranial vault and midface are monitored closely by 3-D CT scans, as well as clinical observation. Although fronto-orbital advancement provides excellent decompression of the craniosynostosis and moderate improvement in the shape of the cranial vault in the early postoperative period, continued growth restriction in both the cranial vault and the midface region often produces poor long-term esthetic results in these syndromic patients. If signs of increased ICP, severe exorbitism, or an abnormally shaped cranial vault develop, a second and, occasionally, a third fronto-orbital advancement and cranial vault remodeling procedure are indicated [Figure 9].

Figure 9A

Pre-op Crouzons syndrome

Bicoronal fl ap and exposure

Intra-op marking of planned osteotomy

Barrel Steeve osteotomy

Bench osteosynthesis

Final osteosynthesis

Post op awaiting midface correction

Surgical Correction of the Midface Deformity

The first attempt to correct the midface deformity in a syndromic craniosynostosis patient was made by Sir Harold Gillies, who performed a Le Fort III procedure. The procedure, initially abandoned by Gillies, was later popularized by Tessier. The Le Fort II can be performed alone, or, if all permanent teeth have erupted, in conjunction with a Le Fort I advancement. The monobloc frontofacial advancement procedure, which involves the advancement of the Le Fort III fragment in coordination with the frontal bar, was developed by Ortiz-Monasterio. The monobloc procedure, while offering the advantage of simultaneously correcting the supraorbital and midface deformity, is associated with greater blood loss and a higher infection rate, which is most probably the result of the direct communication between the cranial and nasal cavities. This increased risk prevents the monobloc procedure in the neonatal period. Currently, the Le Fort III via a subcranial approach is probably the procedure of choice for correcting midface deformity, although good results with the monobloc, especially via distraction (see Distraction Osteogenesis of the Midface later in the article), have been reported.

The exact timing of midface correction remains a controversy among craniofacial surgeons. Some craniofacial centers advocate early surgical correction, between the ages of 4 and 7 years; others prefer to wait until skeletal maturity is reached, at around puberty, unless airway obstruction or severe exorbitism dictates the need for early surgery. The advocates of delayed surgical corrections cite evidence of a high incidence of recurrent class III malocclusion in patients who undergo surgery earlier, often requiring a secondary Le Fort III procedure in the teenage years. Our group is also a proponent of this scheme (4–9 years). Advocates of early correction of the midface deformity believe that the overall esthetic improvement will have a significant and positive psychological effect on these children and improve their self-esteem, and they accept a secondary Le Fort III or monobloc osteotomy as a standard step in the treatment of these patients.

Distraction Osteogenesis of the Midface

In recent years, an alternative to the one-stage Le Fort III or monobloc procedure has been developed. Because the overlying soft-tissue envelope may physically limit the amount of advancement possible and contribute to bony relapse, advancement via gradual distraction osteogenesis, initially used in the appendicular skeleton and mandible, has been employed. The procedure involves a standard LeFort III or monobloc osteotomy, without acute advancement, with semiburied placement of an external or semiburied distractor. This device allows for slow stretching/adaptation of the soft tissue and advancement of the face, while new bone forms in the osteotomy gaps. From day five to day seven, postoperatively, after early callus has occurred at the osteotomy site, the device is activated, allowing for an advancement of 1 mm per day until the desired forward movement is achieved. This is followed by a period of several months during which the new bone formed in the osteotomy gaps is allowed to consolidate (calcification of the osteoid). Distractor removal is then performed.

Advantages of distraction include (a) less blood loss and shorter operative time at the initial procedure; (b) greater advancement (up to 20 mm or more) as compared to standard advancement techniques (6–10 mm maximum); (c) absence of need for bone grafts as new bone forms at the osteotomy sites (hence the term distraction osteogenesis); (d) less risk of infection with the monobloc procedures; and (e) less relapse. Disadvantages include (a) prolonged time needed for distraction and consolidation; (b) need for a second procedure to remove the buried devices; and (c) need for wearing an external device for a prolonged period. We do not have any experience in this method.

Orthognathic Surgery

The abnormal patterns of facial growth in children with craniosynostosis syndromes often result in significant dentofacial deformities. The class III malocclusion, secondary to midface retrusion, is the most commonly seen deformity and often develops despite appropriate midface surgical treatment. The team approach to the management of these jaw abnormalities usually involves an orthodontist, a dentist, and a craniofacial surgeon. Following the completion of growth of both the maxilla and the mandible and any needed presurgical orthodontic therapy, surgical correction with at least a Le Fort I osteotomy with a sliding genioplasty may be indicated. These surgical procedures are usually performed between the ages of 14 and 18 years, when the facial skeleton is mature.

Final Facial Contouring

At the completion of facial growth and all major osteotomies, contour irregularities of the facial skeleton may still remain. Final contouring procedures are often performed at this time. They include smoothing down irregularities, adding bone grafts or bone substitutes to different areas (e.g., calcium carbonate cements), and resuspending soft tissues such as the midface or canthus.

Conclusion

In the past, children with craniosynostosis syndromes were stigmatized as being mentally challenged because of their craniofacial features, when, in fact, they were often of normal intelligence. The advent of craniofacial surgery techniques, although far from perfect, offer these children a chance of obtaining a more normal facial appearance and the opportunity to grow, develop, and integrate socially with their peers. The application of newer operative techniques to craniofacial surgery, including endoscopic surgery and osteodistraction, is expected to offer improved results with fewer complications. Distractive osteogenesis has yielded promising results in the cranium and midface.

The real future of children with craniosynostosis syndromes, however, lies in the hands of the molecular geneticists. The advances in this field have allowed for the identification of the gene and the associated mutation for several craniosynostosis syndromes. Ultimately, the ability to genetically screen for these DNA mutations will allow for appropriate family counseling and perhaps, in the future, gene therapy for the correction of the mutation.