**2. General considerations**

#### **2.1. Considerations on homology**

It is easy even for a layperson to see that human anatomy and physiology have their equivalence throughout the zoological scale of vertebrates, especially when it comes to tetrapods. It is also not difficult to deduce that the mechanisms of development are similar or even identical, especially when we compare eutherian mammals. However, when we think of genes, genotypes, and their mechanisms of action, there is a tendency to conclude that everything is quite different. Nevertheless, in reality, "our genome" is not as exclusively ours as we generally imagine. Dogs and mice share over 90% of our genes [4], enabling us to suppose that genetic programs that control embryonic development are similar in the three species. Genes with a common evolutionary origin, maintaining the same function in different species, are known as orthologs (**Figure 1**). They are clear evidence that the homology of structures among species also have a molecular base. For instance, the *ADAMTS20* gene is one of the necessary genes for the normal palatogenesis of mice, to the extent that homozygous individuals for a mutation with loss of function have a palatal cleft [5]. Recently, a recessive mutation in the canine ortholog was identified in dogs with a cleft palate [6].

Knowledge of the developmental biology and genetics of one species helps us to understand those of another. Much has been learned regarding craniofacial morphogenesis by studying chickens and mice [7–9]. The dog, which has contributed so much to the development of

**Figure 1.** Shared genome. Examples of orthologs with the respective chromosomal assignment in the dog (CFA) and man (HSA). In two of them (*ADAMTS20* and *DLX6*), mutations are known that cause cleft lip and palate in a breed of dogs, while in the other three, mutations are known that have been associated with cleft lip and palate in humans.

surgical techniques used today to correct oral defects, can also help to expand our knowledge of the pathogenesis and genetics of orofacial defects.

#### **2.2. Considerations on the morphogenesis of the lip and palate**

**2. General considerations**

144 Designing Strategies for Cleft Lip and Palate Care

**2.1. Considerations on homology**

identified in dogs with a cleft palate [6].

It is easy even for a layperson to see that human anatomy and physiology have their equivalence throughout the zoological scale of vertebrates, especially when it comes to tetrapods. It is also not difficult to deduce that the mechanisms of development are similar or even identical, especially when we compare eutherian mammals. However, when we think of genes, genotypes, and their mechanisms of action, there is a tendency to conclude that everything is quite different. Nevertheless, in reality, "our genome" is not as exclusively ours as we generally imagine. Dogs and mice share over 90% of our genes [4], enabling us to suppose that genetic programs that control embryonic development are similar in the three species. Genes with a common evolutionary origin, maintaining the same function in different species, are known as orthologs (**Figure 1**). They are clear evidence that the homology of structures among species also have a molecular base. For instance, the *ADAMTS20* gene is one of the necessary genes for the normal palatogenesis of mice, to the extent that homozygous individuals for a mutation with loss of function have a palatal cleft [5]. Recently, a recessive mutation in the canine ortholog was

Knowledge of the developmental biology and genetics of one species helps us to understand those of another. Much has been learned regarding craniofacial morphogenesis by studying chickens and mice [7–9]. The dog, which has contributed so much to the development of

**Figure 1.** Shared genome. Examples of orthologs with the respective chromosomal assignment in the dog (CFA) and man (HSA). In two of them (*ADAMTS20* and *DLX6*), mutations are known that cause cleft lip and palate in a breed of dogs, while in the other three, mutations are known that have been associated with cleft lip and palate in humans.

Orofacial development is a sequence of events in space and time that involve cellular multiplication, migration and differentiation, tissue fusion, and apoptosis and are dependent on the action of various signaling molecules and transcription factors [10].

The primitive mouth is called the stomodeum. It emerges as a slight depression on the ectodermal surface, delimited by mesenchymal structures where cells from the neural crest proliferate. Although these cells are ectodermal in origin, they settle and integrate with the mesenchyme of the head of the embryo. They are fundamental to the development of the craniofacial structures. Five structures surround the stomodeum: frontonasal prominence, from which the primary palate will originate; right and left maxillary prominences, from which the secondary palate will originate; and right and left mandibular prominences, from which the mandible will originate (**Figure 2**). The maxillary and mandibular prominences are derived from the first branchial arch [10, 11].

#### *2.2.1. Formation of the primary palate*

The primary palate is the primordium of the hard palate (incisive bone) rostrally located at the incisive fissures (incisive foramen in humans). During development, the frontonasal prominence forms a pair of lateral and medial nasal processes. The fusion of the lateral and medial parts of each process delimits the nasal cavities that are forming. The medial processes are then lengthened and projected between the maxillary prominences, are fused with them, and transformed into the primary palate and medial part of the upper lip [11].

#### *2.2.2. Formation of the secondary palate*

The secondary palate is the primordium of the palate caudally located at the incisive fissures (hard palate and soft palate, so-called because its formation is completed after the formation of the primary palate). Initially, the maxillary prominences are projected vertically by the sides of the tongue, and are then raised and projected horizontally on the tongue until they meet. A fusion then occurs between the two in the medial line forming a continuous epithelial seam, which will subsequently disappear. Rostrally, the secondary palate is also fused with the primary palate and, dorsally, with the projection (nasal septum) formed by the united medial nasal processes. The maxillary prominences also form the lateral parts of the upper lip [11].

At approximately 23 days of gestation, in the canine embryo it is possible to see the frontonasal, maxillary, and mandibular prominences. At approximately 28 days, the first ossification of the maxilla and mandible occurs [12].

### **3. Medical aspects**

#### **3.1. Frequency**

A cleft lip and/or palate can affect purebred dogs or mongrels. Any canine breed can be affected, especially if we consider cleft lip and palate caused by environmental teratogens. However, the relatively frequent occurrence in some breeds indicates a strong contribution of genetic factors [13].

Indeed, certain breeds of dog are more likely to have cleft lip and palate, especially brachycephalic dogs [14]. At least, this is the clear impression of numerous veterinary practitioners who work with small animals worldwide. Unfortunately, no statistics are yet available that enable definitive statement regarding frequency in different breeds, nor in canine species as a whole.

In boxers, a frequency of 0.6% has been recorded, while in beagles has been 0.11%, and in Pyrenees shepherd dogs, 2.2%. In Portuguese water dogs, cleft palate has been reported in 2.3% of litters [15–18].

In some cases, the high frequency observed at veterinary clinics in certain breeds may be due to the popularity of those breeds at a given time. It is also possible that the frequency is high in certain lines due to constant inbreeding, but not high in the breed as a whole. In a lineage of old Spanish pointer dogs a frequency of 15–20% was found [19].

**Table 1** shows the breeds that are considered as having a predisposition to oral clefts or for which cases have been registered.


**Table 1.** Breeds with records of CL/P.

#### **3.2. Classification**

are then lengthened and projected between the maxillary prominences, are fused with them,

The secondary palate is the primordium of the palate caudally located at the incisive fissures (hard palate and soft palate, so-called because its formation is completed after the formation of the primary palate). Initially, the maxillary prominences are projected vertically by the sides of the tongue, and are then raised and projected horizontally on the tongue until they meet. A fusion then occurs between the two in the medial line forming a continuous epithelial seam, which will subsequently disappear. Rostrally, the secondary palate is also fused with the primary palate and, dorsally, with the projection (nasal septum) formed by the united medial nasal processes. The maxillary prominences also form the lateral parts of

At approximately 23 days of gestation, in the canine embryo it is possible to see the frontonasal, maxillary, and mandibular prominences. At approximately 28 days, the first ossification

A cleft lip and/or palate can affect purebred dogs or mongrels. Any canine breed can be affected, especially if we consider cleft lip and palate caused by environmental teratogens. However, the relatively frequent occurrence in some breeds indicates a strong contribution

Indeed, certain breeds of dog are more likely to have cleft lip and palate, especially brachycephalic dogs [14]. At least, this is the clear impression of numerous veterinary practitioners who work with small animals worldwide. Unfortunately, no statistics are yet available that enable definitive statement regarding frequency in different breeds, nor in canine spe-

In boxers, a frequency of 0.6% has been recorded, while in beagles has been 0.11%, and in Pyrenees shepherd dogs, 2.2%. In Portuguese water dogs, cleft palate has been reported in

In some cases, the high frequency observed at veterinary clinics in certain breeds may be due to the popularity of those breeds at a given time. It is also possible that the frequency is high in certain lines due to constant inbreeding, but not high in the breed as a whole. In a

**Table 1** shows the breeds that are considered as having a predisposition to oral clefts or for

lineage of old Spanish pointer dogs a frequency of 15–20% was found [19].

and transformed into the primary palate and medial part of the upper lip [11].

*2.2.2. Formation of the secondary palate*

146 Designing Strategies for Cleft Lip and Palate Care

of the maxilla and mandible occurs [12].

the upper lip [11].

**3. Medical aspects**

of genetic factors [13].

cies as a whole.

2.3% of litters [15–18].

which cases have been registered.

**3.1. Frequency**

Successful communication between professionals (veterinary practitioners, geneticists, surgeons, dentists, etc.) who treat patients with CL/P depends on an appropriate and correct registration of these abnormalities adhering to common criteria by everyone involved. Thus, the adoption of a classification is highly important. Furthermore, a consistent register based on a classification helps to establish the cause, planned treatment, prognosis, and studies of comparative anatomy [24].

The different classifications used in human medicine can be adapted for use with dogs, as has been done by some researchers based on the first classifications of human oral clefts [24, 25]. Many of the classifications of human clefts are modifications of the classification of Kernahan and Stark [26], which will be adopted here for the purposes of this chapter. It is based on the morphology and pattern of embryonic development of mammals. The clefts are clustered into three groups, each with three subgroups, with all of them considering the degree of impairment of the structures as total or partial (**Figures 3** and **4**):

**Figure 3.** Types of cleft. In each group, complete unilateral or bilateral clefts are shown. However, a cleft from Group I can be left- or right-sided and affect only the lip, the lip and the alveolar process, or include the entire extension of the primary palate, as shown in the illustration. Likewise, a cleft from Group II may affect only the soft palate or the soft palate and the hard palate.

**Figure 4.** Dogs with nonsyndromic (A–C) and syndromic (D) clefts. (A) Left-sided unilateral cleft, affecting the upper lip, alveolar process, and incisive bone (primary palate); (B) cleft palate only; (C) bilateral cleft (upper lip, hard palate, and soft palate); (D) anophthtalmia and CLP. Photographs (A–C) reprinted from Moura and Pimpão [35].

Group I. Primary cleft palate (total or partial impairment)

1 – unilateral left or right; 2 – medial; 3 – bilateral

Group II. Secondary cleft palate only

1 – total; 2 – partial; 3 – submucous

Group III. Primary and secondary palate (total or partial impairment)

1 – unilateral left or right; 2 – medial; 3 – bilateral

The criteria for defining a cleft as partial (incomplete) or total (complete) is subjective. Thus, with broader objectives, especially for epidemiological studies and minute comparison with human clefts, we suggest using the numerical system adapted by Schwartz et al. [27] from the striped Y of Kernahan [28], known as the RPL system, or one of the others that are available.

#### **3.3. Etiology**

morphology and pattern of embryonic development of mammals. The clefts are clustered into three groups, each with three subgroups, with all of them considering the degree of impair-

**Figure 3.** Types of cleft. In each group, complete unilateral or bilateral clefts are shown. However, a cleft from Group I can be left- or right-sided and affect only the lip, the lip and the alveolar process, or include the entire extension of the primary palate, as shown in the illustration. Likewise, a cleft from Group II may affect only the soft palate or the soft

**Figure 4.** Dogs with nonsyndromic (A–C) and syndromic (D) clefts. (A) Left-sided unilateral cleft, affecting the upper lip, alveolar process, and incisive bone (primary palate); (B) cleft palate only; (C) bilateral cleft (upper lip, hard palate,

and soft palate); (D) anophthtalmia and CLP. Photographs (A–C) reprinted from Moura and Pimpão [35].

ment of the structures as total or partial (**Figures 3** and **4**):

148 Designing Strategies for Cleft Lip and Palate Care

palate and the hard palate.

Cleft lip and/or palate (CL/P) in dogs, as in humans, are etiologically heterogeneous, and can be caused by genetic factors, environmental factors, or a combination of these two groups of factors [29, 30].

Mutations in different genes, both in murine models and human beings, have been associated with CL/P [29]. As these genes have the respective homologs that are also present in the canine genome, the same situation is expected to occur in dogs (see Section 4).

The environment of an embryo is represented by the amniotic sac, uterus, maternal body, and the place where the mother lives. Thus, the potentially negative influences of this environment include amniotic abnormalities, uterine abnormalities, maternal metabolic disease, viruses, chemical substances swallowed by or administered to the mother, and maternal exposure to chemical or physical environmental pollutants [31]. Few studies of dogs associate a given environmental factor to oral clefts. Furthermore, these studies focus on substances administered to the mother of the affected dogs during gestation, such as 6-diazo-5-oxo-l-norleucine, aspirin, and vitamin A [32–34]. However, it should be remembered that in the case of aspirin and vitamin A, excessive doses were used, much higher than therapeutic doses. Based on the data obtained in other species (mice, rats, cats, goats, etc.), or personal impressions, it has been suggested that maternal exposure to various substances such as hydroxyurea, griseofulvin, anabasine, metronidazole, primidone, sulphonamides, and corticosteroids can cause oral clefts in dogs [30]. Indeed, as the morphogenic processes are highly conserved [35], the same causes of oral dysmorphogenesis known in man can also be found in other species of mammals, including dogs, and vice versa (**Table 2**).

The interaction between genetic and environmental factors is a known underlying phenomenon of the development of certain phenotypes [38]. Evidence has already been found in humans, linking certain genetic markers to CL/P. For example, maternal smoking in combination with the variants of the *GSTT1* and *IRF6* genes increases the risk of clefts [29]. It should be remembered once again that dogs and humans have high genomic homology and share the same environment [1]. Therefore, similar or even identical interactions may occur.


**Table 2.** Presumed or confirmed risk factors that have been associated with CL/P in humans.

#### **3.4. Pathogenesis**

Refs. [29, 36, 37].

there are discrepancies between the studies.

Due to its etiology, a cleft lip or palate may be the result of an originally abnormal development process or negative interference in a normal development process, corresponding to the concepts of malformation and disruption, respectively, used in dysmorphology [35].

The heterogeneous etiology, in cases of malformation and disruption, assumes varied mechanisms in the development of CL/P. While some mechanisms impair the morphogenesis of various structures in addition to the palate, resulting in syndromic clefts, others act only in the palatogenesis, resulting in nonsyndromic clefts [29, 35].

Developmental field (or morphogenic field) theory aids understanding because different factors can cause the same type of defect. In the early stages, the whole embryo represents a developmental field (primary field). Later, a developmental field is a region or part of the body of the embryo which responds as a coordinated unit to embryonic induction and gives rise to multiple or complex anatomic structures [39, 40]. The induction depends on influences, both physical and chemical, that one developing tissue has on another (or others) in embryogenesis [39]. Developmental fields are systems that control the progressive differentiation of the structure and size, in addition to the temporal and spatial distribution of complex organ components [40]. During blastogenesis, the interactions of the primary field (embryo) generate the progenitor fields (primordia of the final structures) that, in turn, create the secondary fields that produce the final structures during organogenesis [41].

Defects in a structure or in part of the body result from disturbances in one or more secondary fields and are known as monotopic field defects, such as nonsyndromic oral clefts. Multiple defects are the result of disturbances in the primary field or progenitor fields, as occurs in individuals with various defects, including CL/P (syndromic clefts). Correlated defects that emerge early during blastogenesis and affecting structures in different parts of the body are polytopic field defects [41].

At any time during embryogenesis, disturbances in the developmental fields can reflect negatively on fusion mechanisms between the lateral and medial nasal processes, and the medial nasal processes with the maxillary processes (Group I clefts); and/or the mechanisms of development, elevation, and fusion of the palatal shelves and the disappearance of the midline epithelial seam (clefts in Groups II and III).

#### **3.5. Patient evaluation**

**3.4. Pathogenesis**

Ionizing radiation

Refs. [29, 36, 37].

Due to its etiology, a cleft lip or palate may be the result of an originally abnormal development process or negative interference in a normal development process, corresponding to the

Obs.: Not all the risk factors presented in this table are definitely associated with CL/P, and further studies are required. Several factors (amoxicillin, corticosteroids, maternal obesity, stress, etc.) have not shown a consistent association and

The heterogeneous etiology, in cases of malformation and disruption, assumes varied mechanisms in the development of CL/P. While some mechanisms impair the morphogenesis of various structures in addition to the palate, resulting in syndromic clefts, others act only in

Developmental field (or morphogenic field) theory aids understanding because different factors can cause the same type of defect. In the early stages, the whole embryo represents a developmental field (primary field). Later, a developmental field is a region or part of the body of the embryo which responds as a coordinated unit to embryonic induction and gives rise to multiple or complex anatomic structures [39, 40]. The induction depends on influences, both physical and chemical, that one developing tissue has on another (or others) in embryogenesis [39]. Developmental fields are systems that control the progressive differentiation of the structure and size, in addition to the temporal and spatial distribution of complex organ components [40]. During blastogenesis, the interactions of the primary field (embryo) generate the progenitor fields (primordia of the final structures) that, in turn, create the secondary

Defects in a structure or in part of the body result from disturbances in one or more secondary fields and are known as monotopic field defects, such as nonsyndromic oral clefts. Multiple defects are the result of disturbances in the primary field or progenitor fields, as occurs in

concepts of malformation and disruption, respectively, used in dysmorphology [35].

the palatogenesis, resulting in nonsyndromic clefts [29, 35].

Amoxicillin Maternal hyperthermia

Cholesterol deficiency Retinoic acid Corticosteroids Smoking Folate deficiency Stress

150 Designing Strategies for Cleft Lip and Palate Care

Fluconazole Viral infections

Hyperglycemia Zinc deficiency

there are discrepancies between the studies.

High parental age Vitamin B complex deficiency

Maternal obesity

Maternal alcohol consumption Others (occupational exposures, environmental pollutants)

**Table 2.** Presumed or confirmed risk factors that have been associated with CL/P in humans.

Anticonvulsants (diazepam, phenytoin, phenobarbital,

topiramate)

fields that produce the final structures during organogenesis [41].

The diagnosis is conducted by visual inspection of the entire extension of the oral cavity, from the premaxilla (incisive bone) to the soft palate. Without this precaution, smaller clefts may go undetected, especially those that affect the soft palate only.

Cleft lip is evident, however, it indicates the need for a thorough and detailed examination of the oral cavity of the patient and the entire organism in search of other congenital abnormalities to determine whether the cleft is an isolated (nonsyndromic) defect or part of a larger (syndromic) condition.

In newborns, difficulty in nursing, nasal reflux of milk, and fault in development are frequent clinical signs. In older patients, in addition to delayed development, choking, coughing, and sneezing during feeding are common. Nasal discharge is also frequent, but the existence of one or more clinical signs and their intensity depends on the location and gravity of the cleft. It is important to be attentive to clinical manifestation resulting from complications, especially signs of pneumonia, a condition that requires immediate treatment.

Detailed record of the oral cleft is essential for adequate planning of treatment, evaluation of postsurgery progress, and studies with different purposes.

Evaluation of the general condition of the patient may include routine laboratory tests and X-rays. Computerized tomography may be useful for planning surgical treatment [3]. The simultaneous existence of oral cleft and other congenital defects justifies a karyotype test.

Irrespective of the existence of obvious abnormalities or clinical signs, inspection of the oral cavity should be part of the physical examination of all newborns.

#### **3.6. Complications**

Cleft lip in general means no complications or complications limited to suction problems. However, clefts that affect the incisive bone and, above all, those that affect the secondary palate cause problems of feeding, breathing, and malocclusion. They cause rhinitis, rhinosinusitis, and occasionally otitis media [42, 43]. They can also cause aspiration pneumonia with risk of death. Malnutrition, dehydration, and accumulation of food in the cleft are commonplace.

Unlike in humans and for obvious reasons, difficulty in emitting sounds is not important in dogs and speech defects do not exist.

#### **3.7. Treatment**

Cleft lip and palate require corrective surgery to enable adequate function and for esthetic reasons. However, the decision to undergo surgery falls to the owner of the dog. Although many opt for euthanasia, every day, people seek veterinary clinics to inquire about treatment for a dog born with a CL/P.

If the owner opts for treatment, it is necessary for him to be fully aware of the intensive work involved before the patient is old enough for surgery. It is also important to give the owner careful guidelines regarding feeding and cleaning procedures for his dog. He should also be warned of the need to be constantly on the lookout for possible complications. Clefts that affect only the lip or the lip and the alveolar process require little of the owner, but the more extensive clefts may require a lot of dedication.

An efficient and minimally invasive technique for feeding dogs with a cleft palate was described by Martínez-Sanz et al. [19] using baby bottle nipples and customized palatal prostheses made of dental thermoplastic plates. During the breastfeeding period, dogs were fed with a commercial maternal milk substitute using a baby bottle with a customized nipple. After weaning, which occurred during the fifth week of life, palatal prostheses were made every week in keeping with the development of the dogs. The palatal prosthesis was kept in the mouth during the day and removed at night. The technique did not impede oral development and the materials used are easily obtained from dental suppliers. The cost is relatively low and accessible to most veterinary clinics [19].

In cases of severe clefts, it is necessary for the newborn to be fed through a stomach tube to ensure its height and weight development and good nourishment. It may even be necessary to create an esophageal or gastric stoma for feeding and hospitalize the patient [30]. These procedures can be found in several textbooks of veterinary hospital techniques.

In any situation, the owner must be duly trained to deal with the patient's condition and clean the oral cavity adequately after feeding. Alternatively, the owner should take the dog to a veterinary clinic every day for adequate care. A collaborative, patient, and well-informed owner is essential for dogs with cleft lip and palate to develop and be ready for a surgical procedure.

The age that most surgeons consider appropriate for the first corrective procedure is between 4 and 6 months, i.e., it is advisable to await permanent dentition eruption. Before this time, dental development may be harmed. It is also important to consider that oral clefts tend to diminish with growth and become stable at around 6 months [30, 44, 45].

The surgery should be carefully planned and all preoperative care should be taken, including stabilization of the nutritional status and the solution of any complications that may arise. Rhinitis or rhinosinusitis should be treated with antibiotics and secretolytic agents. The same medication is used to treat aspiration pneumonia together with oxygen, bronchodilators, and, in some cases, corticosteroids [30].

Several techniques are available to correct cleft lip and cleft palate, ranging from those that use a mucosal flap or mucoperiosteal flap to autologous bone grafts and prostheses in the case of larger clefts. There are also promising procedures that use mesenchymal stem cells of the iliac bone with hydroxyapatite particles [44, 46–49]. When the correction is done in stages, the functional rehabilitation and esthetic results are better [50]. Although the main purpose is the rehabilitation of the patient, veterinary procedures in plastic surgery and dentistry are now available and would provide a really good esthetic effect in a final step.

Like all surgery, postoperative care is essential for success. Thus, supportive measures and the administration of antibiotics, analgesics, and antiinflammatory medicine should be followed strictly. Care should also be taken regarding the patient's feeding and hygiene.

### **3.8. Prevention**

**3.7. Treatment**

for a dog born with a CL/P.

152 Designing Strategies for Cleft Lip and Palate Care

extensive clefts may require a lot of dedication.

low and accessible to most veterinary clinics [19].

in some cases, corticosteroids [30].

Cleft lip and palate require corrective surgery to enable adequate function and for esthetic reasons. However, the decision to undergo surgery falls to the owner of the dog. Although many opt for euthanasia, every day, people seek veterinary clinics to inquire about treatment

If the owner opts for treatment, it is necessary for him to be fully aware of the intensive work involved before the patient is old enough for surgery. It is also important to give the owner careful guidelines regarding feeding and cleaning procedures for his dog. He should also be warned of the need to be constantly on the lookout for possible complications. Clefts that affect only the lip or the lip and the alveolar process require little of the owner, but the more

An efficient and minimally invasive technique for feeding dogs with a cleft palate was described by Martínez-Sanz et al. [19] using baby bottle nipples and customized palatal prostheses made of dental thermoplastic plates. During the breastfeeding period, dogs were fed with a commercial maternal milk substitute using a baby bottle with a customized nipple. After weaning, which occurred during the fifth week of life, palatal prostheses were made every week in keeping with the development of the dogs. The palatal prosthesis was kept in the mouth during the day and removed at night. The technique did not impede oral development and the materials used are easily obtained from dental suppliers. The cost is relatively

In cases of severe clefts, it is necessary for the newborn to be fed through a stomach tube to ensure its height and weight development and good nourishment. It may even be necessary to create an esophageal or gastric stoma for feeding and hospitalize the patient [30]. These

In any situation, the owner must be duly trained to deal with the patient's condition and clean the oral cavity adequately after feeding. Alternatively, the owner should take the dog to a veterinary clinic every day for adequate care. A collaborative, patient, and well-informed owner is essential for dogs with cleft lip and palate to develop and be ready for a surgical procedure. The age that most surgeons consider appropriate for the first corrective procedure is between 4 and 6 months, i.e., it is advisable to await permanent dentition eruption. Before this time, dental development may be harmed. It is also important to consider that oral clefts tend to

The surgery should be carefully planned and all preoperative care should be taken, including stabilization of the nutritional status and the solution of any complications that may arise. Rhinitis or rhinosinusitis should be treated with antibiotics and secretolytic agents. The same medication is used to treat aspiration pneumonia together with oxygen, bronchodilators, and,

Several techniques are available to correct cleft lip and cleft palate, ranging from those that use a mucosal flap or mucoperiosteal flap to autologous bone grafts and prostheses in the case of larger clefts. There are also promising procedures that use mesenchymal stem cells of the

procedures can be found in several textbooks of veterinary hospital techniques.

diminish with growth and become stable at around 6 months [30, 44, 45].

The prevention of oral clefts in dogs follows the same principles as prevention in humans. In other words, educating people regarding the risk factors and genetic counseling, with appropriate adaptations.

Pregnant dogs should be given a balanced diet and their health should be monitored. They should also be protected from viral agents. The environment where they live should be free of chemical products. Breeders and owners should be warned of the risk to the embryo/fetus from the administration of certain medicines. Before prescribing medicine, veterinary practitioners should check the teratogenic potential of the drug.

In humans, advanced parental age is linked to an increased probability of oral clefts in offspring [51]. However, in dogs, there are not studies on this aspect. Assuming that this is the case with dogs, a preventive measure is to use good sense and avoid crossing very young animals or much older ones.

As in human medicine, in veterinary medicine, mineral and vitamin supplements have been recommended, especially folic acid and vitamins B6 and B12 [52, 53]. However, the results are not definitive and there have been discrepancies between studies [29, 54].

A daily supplement of 5 mg of folic acid in pregnant French bulldogs, beginning on the 15th day and ending on the last day of pregnancy, reduced the frequency of cleft palate by 48.54% in a research period of 18 months [53]. In Boston terriers, a reduction of 76% was observed [52]. In pugs and Chihuahuas, there were reductions of 60 and 66.67%, respectively. A supplement of 5 mg/day was given to pugs and 2.5 mg/day to Chihuahuas from the beginning of estrus to the 40th day of gestation [55].

Considerations on genetic counseling will be given later in Section 4.3.
