Historical Background

According to Boo Chai, the first case of an oblique cleft was recorded in Latin by von Kulmus in I732. Very few anecdotes mention children with craniofacial clefts. Very few children probably survived before the modern medical era.

Epidemiology

The prevalence of all facial clefts, including the more common cleft lip and palate, has been estimated to be 0.127 % (95% CI 0.089–0.182) or 1 in 786 (range 1 in 551 to 1 in 1122) live, stillbirths, and terminations.³ The few data on the rate of oblique clefts on the literature are expressed not in terms of births or pregnancies but as a percentage of all facial clefts. Natsume et al. reviewed these rates from Japan and several other countries. They showed that oblique facial clefts are around 0.22% of all clefts.³³ The same rate was found by Monasterio in Mexico.³⁴

Pathogenesis and Etiology

The precise etiology of the clefting phenomenon is still a matter of debate. Some patients present with impressive facial and limb defects, commonly interpreted as signs of amniotic bands.^35,36 Other classic mechanisms suggested are failure of fusion of facial processes or mesodermal migration.³⁷ The molecular and genetic basis of the CFC is an ever-expanding field. It has been shown recently that cranial neural crest cells regulate the interaction of craniofacial mesoderm structures and thus control the whole musculoskeletal architecture of the face and the cranium.^38,39 The genetic basis of the CFCs was strongly supported by the work by Saadi et al. who showed that SPECC1L is a critical gene that controls facial morphogenesis through the expression of a cytoskeletal cross-linking protein. The authors also demonstrated that mutations on SPECC1L lead to oblique facial clefts.^40,41

Is there any chance for a specific genetic basis for the coexistence of multiple atypical defects in different parts of the body?⁴² This question has been raised since a mouse mutant gene (Disorganization, or Ds), which causes extremely variable sporadic developmental anomalies, was discovered.⁴³ Although this gene has not been identified in humans and the related cases are controversial,⁴⁴ it possible that atypical CFC classically associated with amniotic bands have a genetic basis.

Terminology and Classification

In the past, numerous terms were used to describe CFCs, including cranium bifidum and frontonasal, para-axial, paramedial, oculonasal, orbitonasal, oculofacial, orofacial, oronasal, and otocephalic dysplasia to distinguish the large variety of CFCs.^37,45 This confusing nomenclature stimulated several authors to group CFCs into specific categories. In 1887, Morian was the first to try to organize the main types of CFCs.⁴⁶ In the 1960s and 1970s, Karfik,⁴⁷ Harkins et al.,⁴⁸ and Boo-Chai⁴⁹ proposed new classifications. Although Harkin did not include the midline cleft in his classification, his work was endorsed by the American Association of Cleft and Palate Rehabilitation.⁴⁸

In 1976, Paul Tessier, on the basis of his personal experience with 336 patients with CFCs, published a pure morphologic classification of facial clefts, and this classification was widely accepted as an important descriptive system.⁴⁵ Tessier distinguished 16 clefts distributed above and below a horizontal axis passing through the orbital center (Fig. 7.9). Starting at the midline, clefts numbers 0, 1, 2, 3, 4, and 5 represent defects below the orbital plane. These six clefts may have corresponding defects above the horizontal axis numbered, respectively, as 14, 13, 12, 11, 10, and 9. Clefts 7, 6, and 8 are also found inferiorly but have no correspondence superiorly. Cleft 7 is a mouth commissural defect, cleft 6 is the zygomatic defect of Treacher Collins syndrome, and cleft 8 is located at the lateral angle of the palpebral fissure. Finally, Tessier assigned the number 30 to the extremely rare symphyseal mandibular cleft.⁵⁰

Despite wide acceptance, Tessier’s nomenclature did not entirely replace the classic terms. For instance, cleft 14 is also referred to as frontonasal dysplasia⁵¹ and clefts 3, 4, and 5 and the corresponding numbers 11, 10, and 9 are often named oblique clefts.^{3,35,37,49,51–53} After Tessier, van der Meulen et al. proposed a different classification. Instead of the time-honored word “cleft,” the authors employed the term dysplasia to name a variety of conditions, including blepharoptosis, epicanthus, blepharophimosis, strabismus, dermolipoma, and so on.⁵⁴ Their ideas were somewhat confusing and have not been used. Tessier’s classification is still the most commonly used among craniofacial surgeons.^51,55

Differential Diagnosis

Facial clefts are typically evident prenatally or at birth. As such, the concept of differential diagnosis is not appropriately applied. Instead, newborns who present with CFCs should be evaluated for associated regional and systemic conditions.

Clinical Features

As the orbital cavity is a transition zone between the face and skull, it is not surprising that most facial CFCs directly or indirectly affect the orbits position or their walls and contents. The midline clefts do not cross the orbital space but may have a profound effect on the interorbital distance (Fig. 7.10). This may manifest as true hypertelorism, rather than the more common telecanthus. Clefts 0 to 14 induce a spectrum of soft tissue changes ranging from subtle defects to massive fissures.^37,45,51,56 Starting inferiorly, cleft 0 presents with a median defect of the upper lip and nose and can extend posteriorly as a palatal cleft. The alae nasi are displaced laterally, and the nasal septum is affected (bifid nose). The cephalad progression of the median defect is cleft 14. There is always an expansion of the ethmoid sinus. The distance between the right and left medial walls of the orbits is increased with different degrees of hypertelorism. In severe cases, binocular vision is impossible. Patients have exotropia and amblyopia in the nonfixating eye.

The paramedian clefts 1/13 and 2/12 are not easily distinguished (Fig. 7.11). Cleft 1 is described as starting in the region of the Cupid’s bow and extending through the dome of the alar cartilage. It progresses superiorly as cleft 13 between the nasal bone and the frontal process of the maxilla. According to Tessier, cleft 2 looks similar to number 1.⁴⁵ It is more lateral in location but still on the nose between the tail of the alar cartilage and the alar base. Its superiorly part is cleft 12, located medially to the medial canthus. In both cleft numbers 1 and 2, the lacrimal system and the palpebral fissure are intact. However, there is ethmoidal enlargement, hypertelorism, and encephalocele, depending on the magnitude of the cranial component of the cleft.

The oblique clefts 3, 4, and 5 and their superior counterparts 11, 10, and 9 have a profound effect on the orbit. Cleft 3, known as naso-ocular, nasomaxillary, or oral–nasal–ocular cleft, is considered by some as the most common oblique cleft.^45,51,57 However, Gunther, in 1963, reported that he had seen only four patients with a cleft 3 over a period of 16 years. During this period, 900 new patients with cleft lip and palate were registered in his institution.⁵⁸ Similar to clefts 1 and 2, cleft 3 also starts in the philtrum of the lip and passes between the alar base and medial canthus, reducing the distance between the nose and the medial canthus. The alar cartilage is usually distorted, and the medial canthus is displaced inferiorly (Fig. 7.12). As the lateral wall and the frontal process of the maxillary bone are absent, the lacrimal system is not formed.^58–60 The medial aspect of the orbit, nose, and maxillary sinus are confluent.

Cleft 4 starts in the lip midway at the philtrum and mouth commissure. It spares the nose and crosses on the lower lid laterally to the lacrimal punctum. The impact on the lid fissure is variable, but when the cleft continues cephalad with cleft 10, the eye is severely affected. The lower lid margin is displaced inferiorly (Fig. 7.13).

Cleft 5 is extremely rare.^61–64 In the mouth, it starts in the lateral commissure and extends toward the lateral aspect of the lower lid. The association of this cleft with its cephalad defect (cleft 9)^53,65–67 is probably rarest of all oblique clefts. In his classic paper, Tessier stated that he never had the opportunity to examine a patient with cleft number 9.⁴⁵ There are few descriptions of CFS 5/9.^31,68 Figure 7.14 displays the patient described by Pereira et al.⁴⁴ The combination of lower and upper lid distortion had a profound effect on the corneal surface, and if the fissure were not immediately repaired, the eye would certainly be perforated.

Cleft 7 is a horizontal defect in the lateral mouth commissure and has no effect on the visual system. In contrast, cleft 6 and 8 are classic defects. Cleft 6 is considered an incomplete form of the Treacher Collins syndrome.³⁷ It is a maxillary–zygomatic defect with a lateral coloboma of the lower eyelid⁴⁵ (Fig. 7.15). Finally, CFC 8, which is located horizontally on the lateral canthus, is also exceptional. Some authors consider this cleft to be a variant of both Treacher Collins and Goldenhar syndromes.⁶⁵ In its pure form, the lateral orbital rim and canthus are not formed. The bony defect extends horizontally from the frontozygomatic junction over the temporal region (Fig. 7.16).

Although Tessier’s classification is widely employed as a useful description scheme, nature seems to be more diverse and variable than Tessier’s Cartesian way of thinking. All surgeons who deal with CFCs eventually see patients who present with multiple clefts along atypical axes, which do not follow Tessier’s description associated with anomalies in various organ systems (Fig. 7.16). These defects are puzzling and difficult to interpret.

Investigations

All patients should undergo a complete physical by with a craniofacial team, including a neurosurgeon, an ophthalmologist, a otorhinolaryngologist, and an oral and plastic surgeon. In addition, a geneticist, a pediatrician, and an anesthesiologist should also evaluate the patients. CT and MRI images of the face and cranium should be obtained. Imaging is crucial for surgical planning and to detect any associated facial and CNS anomalies.

Management

The management of CFCs involving the orbit is essentially surgical. Treatment is complex, based on a multistage approach, which usually requires multiple procedures.⁶ As outlined by Monasterio and Taylor, the treatment philosophy involves restoration of craniofacial skeleton, reconstruction of the soft tissue defects maintaining as much as possible the color and texture of aesthetic subunits and minimizing scars.³⁴ Patients should be evaluated by a multidisciplinary team, including pediatric neurosurgeons, ophthalmologists, craniofacial surgeons, otorhinolaryngologists, and buccomaxillofacial specialists. Early procedures are often necessary to treat intracranial abnormalities, restore airways, and provide urgent eye protection.^34,63

A detailed description of the surgical armamentarium used to repair CFCs is beyond the scope of this section. However, some general principles can be extracted from the literature.^{4,6,34,59,62,63,69} Bony defects are repaired with autogeneous grafts. As the defects frequently interconnect the nose, the paranasal sinuses, and the mouth, the use of alloplastic material carries an unacceptable risk of infection. Scars should be placed at the edge of aesthetic subunits. Multiple interdigitating flaps are avoided and replaced as much as possible by advancements flaps with repositioning of the musculature.⁶⁹ Some steps such as correction of hypertelorism by orbital box osteotomy or midface advancement are typically delayed until late adolescence.^6,70 However, the repair of upper eyelid defects is a matter of urgency and must be performed as early as possible.

Fundamental Science

Sutures are special types of skeletal articulations in which the cranial bones are united by fibrous tissue. At birth, all cranial sutures are unfused, allowing a great deal of mobility and overlap of the calvarial bones, particularly during transit through the birth canal.⁷¹ Suture closure is a slow physiologic process. With the exception of the metopic suture (median frontal suture), which is normally fused by the second year of life,⁷² all other cranial sutures start to close later in adult life.⁷¹ The vast majority of synostosis cases are primary. Premature sutural closure can also be caused secondarily by mechanical or deformational forces.⁷³ Metabolic causes such as rickets⁷⁴ are extremely rare.

Table 7.1 displays the starting time of cranial suture closure associated with nonsyndromic craniosynostosis (NSCS) and the main terms used to describe these conditions. In all forms of isolated synostosis, the resulting cranial shape follows Virchow’s law, which states that whenever a suture is prematurely closed, bone growth is reduced perpendicular to the involved suture and increased parallel to the involved suture. Although any cranial suture may undergo synostosis, the orbit is mainly affected when pathologic closure occurs in the metopic and coronal sutures. Early closure of the metopic suture provokes trigonocephaly, whereas synostosis of the coronal suture leads to plagiocephaly or brachicephaly if the closure is respectively unilateral or bilateral.