Clefts of the lip, palate, or both have been described for several species, including dogs,1–3 cats,4 cattle,4,5 horses,6 and people.7,8 These congenital malformations are important because of the degree of dysfunction involved,9 the associated morbidity,10 the complexity of surgical repair,11,12 and their frequency (1.5 to 3.2 cases/1,000 live human births; 1.1 cases/1,000 live Beagle births).9 Although the etiology is complex and not completely understood,7 the embryological events involved appear to be well conserved among mammalian species.13
An important aspect of CLs, CPs, and CLPs is defect morphology.7,8,14–18 From a clinical standpoint, defect morphology is important for surgical planning and may influence the outcome.17 From a scientific perspective, the systematic documentation and classification of defect morphology is important for the conduction of genetic, embryological, or clinical research.7 Defect morphology with respect to CLs, CPs, and CLPs can be complex and can vary among affected individuals. In people, > 150 defect configurations have been estimated as possible on the basis of the anatomic structures involved.19
Many classification systems for oral cleft defects have been proposed over the past few decades in human medicine, but none have been adopted universally.16,20–23 Some are based on the embryological point of defect formation; namely, the primary palate (ie, lip and alveolus) forms before the secondary palate (ie, hard and soft palate). Others are based on the anatomic structures involved (ie, lip, alveolus, hard palate, and soft palate).
Because of their simplicity, embryological systems are commonly used for epidemiological research and clinical coding purposes.24 The simplest approach is to classify defects as CL, CP, or CLP (when both develop simultaneously). However, for surgical applications and phenotype documentation when conducting genetic research, more detailed (and more complex) anatomic documentation is required.
One limitation of many classification systems is the lack of severity indicators. In general, clefts of the lip, alveolus, and hard palate can develop unilaterally or bilaterally.25 Moreover, clefts can develop as total or subtotal in any given anatomic structure and as a microform (ie, mucosal defect with intact underlying functional layer).25 Furthermore, defect morphology and maxillofacial growth and appearance are not always symmetric or harmonious, and the vomer and septum may be deviated or malformed.25,26 Although some classification systems have been developed with an attempt to incorporate these features, no system has been established that is sufficiently versatile yet simple enough for reproducible application in clinical practice and research.
A widely used classification system in use since 1985 is known as LAHSHAL.25,27 In this system, each letter represents an anatomic location (ie, L represents the lip, A represents the alveolus, H represents the hard palate, and S represents the soft palate). The palindromic nature of this term allows recording the affected side (ie, letters to the left of the S represent defects on the right side and vice versa). Because soft palate defects only occur at the midline, a single middle letter is assigned to record this anatomic area. In regard to extent, upper- or lowercase letters are used to represent complete or incomplete defects, respectively. Finally, an asterisk can be added to lowercase letters whenever a microform defect is present. The anatomic form of a defect is thus reflected by the sequence, order, and type of characters recorded for each individual. One of the disadvantages of this system is that it fails to account for shape or relative width of the defects, any abnormalities of the vomer, or asymmetry of facial structures.
Historically, detailed documentation of oral cleft defect morphology was achieved by means of radiography, casts, or both in live patients26 or by histologic examination of cadaveric specimens.25 Current approaches involve the use of CT, CBCT, and other advanced imaging modalities for both medical and scientific purposes.9,28
Defect morphology of CLs, CPs, and CLPs in people has been extensively described. Conversely, in dogs, most reports2,4 involve embryological classification or provide minimal detail regarding the defects. Understanding defect morphology in dogs would help to enhance the quality of care and the conduction of canine or translational research into oral cleft defects. The purpose of the study reported here was to systematically document the morphology of congenitally acquired CLs, CPs, and CLPs in dogs. We hypothesized that defect morphology would vary among affected dogs and that the morphological variations would resemble those reported in human medicine.
Materials and Methods
Animals
The study was designed as a retrospective study involving historical medical records and archived diagnostic and clinical images. Client-owned dogs with CLs, CPs, or CLPs that had not yet undergone corrective surgery were eligible for inclusion. This included dogs brought for treatment of the defects and associated comorbidities to the Dentistry and Oral Surgery Service at the Cornell University Hospital for Animals between November 2012 and May 2016 or to the William R. Pritchard Veterinary Medical Teaching Hospital of the University of California-Davis between June 2007 and May 2016. To be included in the study, dogs were required to have undergone a head CT or CBCT scan as part of standard-of-care diagnostic imaging prior to any surgical procedures involving the oral cavity or face. Data were collected from electronic medical records regarding breed, sex, age, and body weight. Clinical photographs were reviewed to supplement CT or CBCT findings when considered pertinent.
CT imaging
Computed tomography had been performed with a 16-slice scanner,a,b with images acquired with a slice collimation of 0.5 to 0.625 mm. Cone-beam CTc had been performed with a slice collimation of 0.2 mm. The archived multiplanar reconstruction images (bone algorithm and computer-generated 3-D) were reviewed by the same investigator (SP), who used a commercially available image archiving systemd or dental image–manipulating software.e
Cleft characterization
Oral clefts were classified in each dog as CL, CP, or CLP on the basis of gross appearance and CT findings. Anatomic forms of the clefts were also characterized by use of the LAHSHAL classification system, and annotations were made when abnormalities of the vomer or maxillofacial suture lines were detected and asymmetry or protrusion of specific facial structures was evident. Skull type of each dog was determined by multiplying the distance at the widest point between zygomatic arches (width in centimeters, as measured on CT or CBCT images) by 100 and dividing this product by the distance between the prosthion and the inion (cm) to achieve a skull index value.29 The skull index ranges were then used to categorize skull type (> 66.5 for brachycephalic dogs, 45.5 to 66.5 for mesaticephalic dogs, and < 45.5 for dolichocephalic dogs).
The extent of the clefts was recorded independently for each anatomic area affected. Defects were categorized as subtotal or total. Subtotal defects were defined as defects in which the functional layer and mucosa were only partially absent in the corresponding anatomic area and were recorded as a lowercase initial letter of the corresponding anatomic area. Total defects were defined as defects in which the functional layer and mucosa were absent along the entire corresponding anatomic area and were recorded as an uppercase initial letter of the corresponding anatomic area. Detected microforms or submucous defects were recorded with an asterisk. Microform defects were defined as superficial mucosal defects with an intact underlying functional tissue layer (ie, bone or muscle). Submucous defects were defined as defects in which the functional layer was absent but an intact layer of mucosa was present.
Relative width of the clefts was recorded independently for the soft palate and osseous component of the hard palate, but not for the lip or alveolus owing to the lack of reproducible anatomic points of reference. Values were calculated by dividing the width of the defect at its widest point (mm) multiplied by 100, by the width of the entire anatomic area (mm) measured at that particular point. These values were then used to categorize the defects as severe (width extending beyond 50% of the width of the entire anatomic area), moderate (width 25% to 50% of the entire anatomic area), or mild (width < 25% of the entire anatomic area).
The overall shape of clefts of the hard and soft palate was recorded independently by use of computer-generated 3-D images and archived clinical photographs, but not of clefts of the lip or alveolus owing to the lack of reproducible anatomic points of reference. The shape of osseous hard palate defects was categorized as oval, parallel, divergent, pyriform, or asymmetric. The shape of clefts of the soft palate was categorized as parallel or divergent by use of similar images. The location of alveolar clefts relative to adjacent teeth was also noted.
Results
Animals
Thirty-two dogs met the inclusion criteria and were included in the study (Table 1). Fourteen (44%) dogs were female (11 sexually intact and 3 spayed), and 18 (56%) were male (15 sexually intact and 3 castrated). Age at the time of CT (n = 30 dogs) or CBCT (2 dogs) imaging ranged from 2 to 18 months (median, 7 months), and body weight ranged from 0.7 to 31 kg (median, 7.5 kg). Twenty breeds were represented, including Boxer (6 [19%]), English Bulldog (3 [9%]), mixed (3 [9%]), Labrador Retriever (2 [6%]), pit bull type (2 [6%]), Staffordshire Bull Terrier (2 [6%]), and various other breeds represented by only 1 (3%) dog.
Characteristics of 32 client-owned dogs with CL, CP, or CLP that received a CT or CBCT examination of the head.
Dog No. | Breed | Reproductive status | Body weight (kg) at imaging | Age (mo) at imaging | Imaging modality used |
---|---|---|---|---|---|
1 | Chihuahua | Sexually intact female | 1.2 | 12 | CT |
2 | Boxer | Sexually intact male | 10.8 | 7 | CT |
3 | Staffordshire Bull Terrier | Sexually intact male | 6.2 | 7 | CT |
4 | Toy Poodle | Sexually intact male | 1.5 | 5 | CT |
5 | Staffordshire Bull Terrier | Sexually intact male | 4.1 | 5 | CT |
6 | Boxer | Sexually intact female | 11.8 | 7 | CT |
7 | Labrador Retriever | Castrated male | 31 | 12 | CT |
8 | English Bulldog | Sexually intact male | 3.6 | 4 | CT |
9 | Boxer | Spayed female | 13.5 | 7 | CT |
10 | Maltese | Sexually intact male | 0.7 | 18 | CT |
11 | French Bulldog | Sexually intact male | 3.4 | 3 | CT |
12 | English Bulldog | Sexually intact male | 7.2 | 4 | CT |
13 | Boxer | Sexually intact female | 21.2 | 12 | CT |
14 | Pit bull type | Sexually intact female | 6.5 | 3 | CT |
15 | Boxer | Sexually intact male | 7 | 4 | CT |
16 | Mixed | Sexually intact female | 6 | 4 | CT |
17 | Husky mix | Sexually intact male | 9.2 | 4 | CT |
18 | German Shorthair Pointer | Sexually intact male | 10.5 | 5 | CT |
19 | Mixed | Sexually intact female | 7.8 | 5 | CT |
20 | Mixed | Castrated male | 5.1 | 9 | CT |
21 | English Bulldog | Sexually intact female | 7 | 6 | CT |
22 | American Bulldog | Sexually intact male | 1.4 | 2 | CT |
23 | Yorkshire Terrier | Sexually intact female | 0.7 | 7 | CT |
24 | Boston Terrier | Sexually intact female | 11.7 | 7 | CT |
25 | Labrador Retriever | Sexually intact male | 30.7 | 15 | CT |
26 | Vizsla | Sexually intact male | 16.2 | 7 | CT |
27 | Golden Retriever | Sexually intact female | 19.8 | 7 | CT |
28 | Great Dane | Sexually intact female | 13.2 | 3 | CT |
29 | Pit bull type | Castrated male | 13.9 | 6 | CBCT |
30 | Cocker Spaniel | Spayed female | 8.3 | 10 | CT |
31 | Pomeranian-Chihuahua cross | Spayed female | 3.3 | 8 | CBCT |
32 | Boxer | Sexually intact male | 18.9 | 7 | CT |
Morphological assessments
Skull type was classified as brachycephalic in 18 (56%) dogs and mesaticephalic in 14 (44%) dogs; no dolichocephalic dogs were included in the study sample. In terms of cleft type, a CP was identified in 23 (72%) dogs, CLP in 4 (12%) dogs, and CL in 5 (16%) dogs (Table 2). On the basis of the LAHSHAL classification, 9 distinct anatomic forms of oral clefts were identified (Figure 1).
Skull type, cleft type, and defect morphological characteristics of the dogs in Table 1.
Relative width of defect | Shape of defect | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Cleft type, by skull type | Dog No. | LAHSHAL classification | Vomer abnormality | Right hard palate | Soft palate | Left hard palate | Hard palate | Soft palate | Asymmetric facial growth | Incisive bone protrusion | Nonfused incisivomaxillary and vomeroincisive sutures |
Brachycephalic | |||||||||||
CP | 1 | — — H S H — — | + | 2 | 2 | 2 | Parallel | Divergent | – | – | – |
10 | — — H S H — — | + | 2 | 3 | 2 | Parallel | Divergent | – | – | – | |
22 | — — H S H — — | – | 1 | 1 | 1 | Parallel | Parallel | – | – | – | |
9 | — — H S H — — | + | 3 | 1 | 3 | Oval | Parallel | – | – | – | |
12 | — — H S H — — | + | 3 | 1 | 3 | Oval | Parallel | – | – | – | |
32 | — — H S H — — | + | 3 | 1 | 3 | Oval | Parallel | – | – | – | |
6 | — — H S H — — | – | 2 | 1 | 2 | Oval | Parallel | – | – | – | |
15 | — — H S H — — | + | 3 | 2 | 3 | Divergent | Parallel | – | – | – | |
21 | — — H S H — — | + | 2 | 1 | 2 | Divergent | Parallel | – | – | – | |
11 | — — H S H — — | – | 2 | 2 | 2 | Pyriform | Divergent | – | – | – | |
CL | 13 | — — — — — A L | + | 0 | 0 | 0 | No defect | No defect | + | – | + |
24 | L A — — — A L | – | 0 | 0 | 0 | No defect | No defect | – | + | + | |
29 | — — — — — A L | – | 0 | 0 | 0 | No defect | No defect | + | – | + | |
31 | — — — — — a* L | – | 0 | 0 | 0 | No defect | No defect | + | – | + | |
CLP | 2 | L A h S h A L | + | 2 | 2 | 2 | Pyriform | Divergent | – | – | + |
3 | L A H S H A L | + | 2 | 2 | 2 | Pyriform | Parallel | – | + | + | |
8 | L A H S — — — | + | 1 | 1 | 0 | Asymmetric | Parallel | + | – | + | |
14 | — — H S H A L | + | 0 | 2 | 2 | Pyriform | Parallel | + | – | + | |
Mesaticephalic | |||||||||||
CP | 25 | — — h S h — — | + | 1 | 2 | 1 | Pyriform | Parallel | – | – | + |
7 | — — H S H — — | + | 3 | 1 | 3 | Pyriform | Parallel | – | – | – | |
18 | — — H S H — — | + | 2 | 1 | 2 | Pyriform | Parallel | – | – | – | |
26 | — — H S H — — | + | 3 | 2 | 3 | Pyriform | Parallel | – | – | – | |
27 | — — H S H — — | + | 2 | 2 | 2 | Pyriform | Parallel | – | – | – | |
16 | — — H S H — — | + | 2 | 3 | 2 | Pyriform | Divergent | – | – | – | |
19 | — — H S H — — | + | 2 | 3 | 2 | Pyriform | Divergent | – | – | – | |
20 | — — H S H — — | + | 3 | 3 | 3 | Pyriform | Divergent | – | – | – | |
17 | — — H S H — — | + | 1 | 3 | 1 | Asymmetric | Divergent | + | – | – | |
28 | — — H S H — — | + | 1 | 1 | 1 | Divergent | Divergent | – | – | – | |
4 | — — H S H — — | – | 2 | 2 | 2 | Pyriform | Divergent | – | – | – | |
5 | — — H S H — — | – | 1 | 3 | 1 | Parallel | Divergent | – | – | – | |
23 | — — h S h — — | – | 2 | 1 | 2 | Parallel | Parallel | – | – | – | |
CL | 30 | L A — — — A L | – | 0 | 0 | 0 | No defect | No defect | + | + | + |
Anatomic form of clefts was classified by use of the LAHSHAL classification system.25,27 Each letter represents an anatomic location (L = lip, A = alveolus, H = hard palate, and S = soft palate). In this diagrammatic classification system, letters to the left of the S represent defects on the right side of the soft palate at midline and vice versa. Uppercase and lowercase letters represent complete or incomplete defects, respectively.
Microform (submucous) defect. + = Present. – = Absent.
Relative width of defects was rated as follows: 0 = no defect, 1 = mild, 2 = moderate, and 3 = severe.
CP—Ten of the 23 (43%) dogs with CP were classified as brachycephalic, and 13 (57%) were classified as mesaticephalic. Two distinct anatomic forms of defect were identified, one of which was detected in 21 (91%) dogs with CP, and the other of which was detected in 2 (9%) dogs. On the basis of relative width, most hard palate defects in dogs with CP were classified as moderate (n = 11 [48%]), followed by severe (7 [30%]) and mild (5 [22%]; Figure 2), and most soft palate defects as mild (10 [43%]), followed by moderate (7 [30%]) and severe (6 [26%]). The most common shape of hard palate defects in dogs with CP was pyriform (10 [43%]), followed by parallel (5 [22%]), oval (4 [17%]), divergent (3 [13%]), and asymmetric (1 [4%]). The most common shape of soft palate defects was parallel (13 [57%]), followed by divergent (10 [43%]; Figure 3).
The vomer was considered malformed, insufficient, or both in 17 (74%) dogs with CP and morphologically normal in 6 (26%) dogs. Facial asymmetry (due to disharmonious midfacial growth) was identified in 1 (4%) dog (dog 17), which also had buccal mucosal adhesions to the lips of unknown origin or relationship to the clefts (Figure 4). The palatine process of the maxillary bones was curved or deviated along the edges of the cleft in 3 (13%) dogs with CP.
CLP—All 4 dogs with CLP were brachycephalic, and each had a distinct anatomic form of defect. A CL was present on the right side only in 1 dog, on the left side only in 1 dog, and bilaterally in 2 dogs. All alveolar clefts were between the second and third incisor teeth. On the basis of relative width, most hard palate defects in dogs with CLP were classified as moderate (n = 3), followed by mild (1), and most soft palate defects were similarly distributed. The most common shape of hard palate defects in dogs with a CLP was pyriform (3), followed by divergent (1). The most common shape of soft palate defects was parallel (3), followed by asymmetric (1).
The vomer was considered malformed, insufficient, or both in all 4 dogs with CLP. Facial asymmetry due to a deviated incisive bone was identified in 2 dogs with CLP. Relative protrusion of the incisive bone was identified in 1 dog. The palatine process of the maxillary bones was curved or deviated along the edges of the cleft in 1 dog with CLP. Deviated permanent incisor teeth, (persistent) deciduous incisor teeth, or both were observed in all 4 dogs, as were nonfused incisivomaxillary and vomeroincisive sutures.
CL—Four of the 5 dogs with CL were brachycephalic, and 1 was mesaticephalic. Three distinct anatomic forms of defect were identified, including a submucous alveolar defect in 1 dog. The CL was present on the left side only in 3 dogs and bilaterally in the other 2 dogs. All alveolar clefts were between the second and third incisor teeth.
The vomer was considered abnormal in 1 dog with CL. Facial asymmetry due to a deviated incisive bone was identified in 4 dogs with CL and relative protrusion of the incisive bone in 2 dogs. Deviated permanent or (persistent) deciduous incisor teeth were identified in all 5 dogs, as were nonfused incisivomaxillary and vomeroincisive sutures.
Discussion
In the study reported here, the morphological features and anatomic variations of CLs, CPs, and CLPs were characterized in a group of 32 dogs prior to surgical treatment. Despite the small sample size, multiple anatomic forms were identified on the basis of the LAHSHAL classification system. Moreover, the number of anatomic forms observed (9 forms in 32 patients) was comparable to that reported for people (14 forms in 50 patients),19 suggesting a similar degree of variability (ie, overall > 150 possible anatomic forms are believed possible).
Interestingly, more anatomic forms of defect were identified in dogs with CLP or CL (7 forms in 9 dogs) than in those with CP (2 forms in 23 dogs), despite the smaller number of dogs in the CLP and CL groups. This discrepancy may have been related to an overall small sample size and not be representative of the larger target population. However, given that, by definition, less anatomic areas are involved in CP than in CLP and CL,9,13 less anatomic combinations and configurations are possible. Regardless, most dogs with CP had the same anatomic form of defect, with only 2 of the 23 dogs having a different form, suggesting that variations in the anatomic form of CP in dogs are uncommon.
In contrast, more variations in defect shape were observed in dogs with CP than in those with CLP, particularly regarding the hard palate. Moreover, the relative width of most hard palate defects was considered moderate or severe in dogs with CP, whereas no defects were considered severe in dogs with CLP. This finding underscored the fact that the LAHSHAL classification system does not account for seemingly clinically important morphological features and highlighted the need to obtain additional information to fully characterize the defect.
From a clinical perspective, the width and shape of a defect are important factors because they have the potential to impact surgical planning and possibly influence the outcome.12,17 The finding that CP appeared to take few anatomic forms in dogs did not necessarily suggest that less technically involved techniques would have been required for repair than with CLPs or CLs or that the prognosis would have been better. From a phenotypic standpoint, when conducting genetic research, anatomic forms, relative widths, and shapes of defects may represent differences in etiopathogenetic mechanisms, and knowledge of these factors would support such research. For example, specific defect shapes have been associated with certain syndromic forms of CP in people and dogs. Although not observed in the present study, a representative example would be the Pierre Robin sequence, which is characterized by U-shaped defects of the hard palate, among other typical maxillofacial findings.7,30 Whether differences in shapes of the defects in the present study represented possible differences in embryological events or disease mechanisms requires additional investigation.
The finding that vomer abnormalities were observed in most dogs with CP and CLP but not CL in the present study was not surprising considering that, by definition, CP and CLP involve a total or partial lack of fusion of the palatal processes of the maxillary bones with the vomer itself.9,13 Vomer and septum abnormalities are clinically relevant because they may limit availability of the nasal mucosa for defect repair and may interfere with nasal cavity function when severely hypoplastic, displaced, or malformed.26
The opposite situation would apply to the incisive bone abnormalities observed, which were identified only in dogs with CLP and CL but not CP. That is, by definition, the incisive bones are not involved in CP but are involved in CLP and CL.9,13 Incisive bone abnormalities accounted for the unharmonious facial growth (ie, facial asymmetry or protrusion) in dogs with CL and CLP, and these abnormalities were likely related to the deviation and eruption abnormalities observed at the incisor teeth of affected dogs. Finally, the finding of nonfused incisivomaxillary and vomeroincisive sutures in all dogs with CL and CLP is clinically relevant because these defects explain the incisive bone instability often observed in affected dogs, particularly those with bilateral clefts of the lip and alveolus. From an embryological standpoint, these findings are of interest because they would suggest that incisivomaxillary and vomeroincisive sutures represent the anatomic location that separates the primary and secondary palate. Historically, controversy has existed regarding the exact location of this anatomic point.9,31
As previously identified in dogs,32 all alveolar clefts in the present study were between the second and third incisor teeth. Also, as previously identified in dogs and people,26,32,33 all dogs in the present study had deviation of permanent or deciduous teeth. Taken together, these findings suggest similar embryological events during lip and alveolus cleft formation in both species. Four of the 5 unilateral clefts of the lip and alveolus in the study dogs were on the left side, which is consistent with reported findings for people27,34 but has not been previously reported for dogs. Such discrepancy in the laterality of lip and alveolus clefts is explained by differences in embryological events during palatogenesis; namely, the left palatal shelf goes into a horizontal position later than the right, allowing a wider timeframe for abnormalities to occur.27
Finally, some comments should be made regarding the skull type and breeds of the dogs included in the study reported here. It has been previously suggested that the incidence of oral clefts is higher in brachycephalic versus nonbrachycephalic dogs, and genetic mechanisms are suspected in some breeds, including Boxer.4,35 The breed distribution of the study dogs would support these suggestions because brachycephalic skull types were the most common and Boxers outnumbered dogs of other breeds. Interestingly, when grouping dogs by cleft type, even though all dogs but 1 with CLP and CL were brachycephalic, brachycephalic dogs accounted for less than half of dogs with CP. Our findings suggested that the incidence of CL and CLP, but not necessarily CP, may be highest in brachycephalic dogs versus dogs with other skull types and that CLs, CPs, and CLPs in general are rare in dolichocephalic dogs. However, a much larger sample size would be required to investigate this possibility.
A limitation of the present study was that dogs that were euthanized or died at an early age (presumably) because of more severe or lethal defects or syndromic forms were excluded. Conversely, clinically milder forms (ie, submucous) may have been under-represented given that dogs with such defects may have had no clinical signs and therefore would not have been brought in for evaluation and eventual treatment.
Findings of the present study suggested that the morphological features of congenitally acquired CLs, CPs, and CLPs in dogs are complex and vary among affected individuals. Cleft morphology may impact surgical planning, so these findings may be useful in that regard and in the conduct of future genetic and other studies involving oral clefts in dogs and people.
Acknowledgments
The authors declare that there were no conflicts of interest. The authors thank Nicholas Roman for his assistance in formatting the tables.
ABBREVIATIONS
CBCT | Cone-beam CT |
CL | Cleft lip |
CLP | Cleft lip and palate |
CP | Cleft palate |
Footnotes
Aquilion LB, Toshiba American Medical Systems, Tustin, Calif.
GE Lightspeed16, GE Medical Systems, Cleveland, Ohio.
NewTom 5G, NewTom, Verona, Italy.
Picture Archiving Communications System, Carestream, Rochester, NY.
Invivo5, Anatomage, San Jose, Calif.
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