The most common congenital malformations in dogs: Literature review and practical guide.

Congenital malformations can affect almost 7% of canine newborns. The increase of commercial dog breeding and inbreeding used to maintain the striking characteristics of each breed, the appearance of malformations has become increasingly common, especially in brachycephalic dogs. The causes are diverse, and include genetic, nutritional, iatrogenic, and infectious factors, often making it difficult to establish a cause-consequence relationship. The high mortality associated with malformations comes not only from the fact that some are incompatible with life, but also because even if many undergo surgical treatment or correction, they require specific management, monitoring, and clinical treatment for an indefinite period of time. The most common malformations such as cleft lip and palate, hydrocephalus and anasarca have been studied for a long time, and it is currently known that brachycephalic dogs have a greater predisposition, however, for other less common conditions as gastroschisis and hypospadias, there is only a few case reports. The appearance of congenital defects in a litter leads to financial losses for the breeder, emotional losses for the owner and the veterinarian and harms the well-being of that individual. For this reason, the aim of this review article is to gather relevant information on the characteristics, diagnosis, and management of the main malformations in puppies. It is essential that the veterinarian is prepared to diagnose and treat these conditions, reducing negative impacts on animals and owners.

Use of a barrier membrane to repair congenital hard palate defects and to close oronasal fistulae remaining after cleft palate repair: seven dogs (2019-2022).

OBJECTIVE: To describe the use of a barrier membrane in dogs for repair of congenital hard palate defects and closure of oronasal fistulae (ONF) remaining after previous cleft palate (CFP) repair. ANIMALS: 7 client-owned dogs. METHODS: The hard palate defect was closed with medially positioned flaps (Von Langenbeck technique) or pedicle flaps (2-flap palatoplasty) and a membrane composed of autologous auricular cartilage from the pinna or allogenous fascia lata underlying the mucoperiosteal flaps. RESULTS: All palate defects were considered to have a high risk of dehiscence based on their type and size and the characteristics of the surrounding tissue. The barrier membrane was used in 5 dogs for repair of congenital hard palate defects and in 2 dogs for closure of ONF remaining after previous CFP repair. Resolution of clinical signs occurred in all cases. Complete success (ie, complete closure of the palate defect and absence of clinical signs) was achieved in 5 dogs (4 with congenital hard palate defects and 1 with an ONF remaining after previous CFP repair). The persistent ONF in 1 dog with functional success (incomplete closure, but no clinical signs) was smaller than prior to surgery. CLINICAL RELEVANCE: Barrier membranes underlying mucoperiosteal flaps may constitute an alternative technique in dogs for repair of congenital hard palate defects and closure of ONF remaining after previous CFP repair.

Surgical treatment for cleft palate in dogs yields excellent outcomes despite high rates of oronasal fistula formation: a narrative review.

Cleft palate is the most common congenital orofacial defect in dogs. Although this topic has been extensively studied in experimental dogs, current literature on clinical patients is limited to case reports and small case series studies with many individual opinions based on experience. This narrative review summarizes the literature of the last 10 years with application to clinical practice, focusing on the preparation of the patient until surgery, options for surgical management, and perioperative complications. Surgical treatment must be performed to obtain separation between the nasal/nasopharyngeal and oral/oropharyngeal passages. This will allow the dog to have independent function and reduce clinical signs associated with food, water, and other foreign material entering the respiratory tract. Surgical treatment has good to excellent outcomes when the procedure is carefully planned and appropriately executed despite the high rates of postoperative oronasal fistula reported.

Surgical closure of cleft palate defects in dogs using a modification of the traditional von Langenbeck technique: 12 cases (2015-2022).

OBJECTIVE: To describe the author's surgical guidelines for the effective use of a modified von Langenbeck technique, utilizing bilateral bipedicle mucoperiosteal flaps in the dog. ANIMALS: 12 client-owned dogs with cleft palate defects of the hard and soft palates. PROCEDURES: 12 dogs with cleft palate were presented to the Angell Animal Medical Center from May 20, 2015, to March 24, 2022. The patient's ages ranged from 5 months to 3 years. All 12 dogs had closure of the hard palate clefts by use of modifications of the original von Langenbeck technique in this prospective study. RESULTS: Successful closure of the cleft (hard and soft) palate defects was achieved in all 12 dogs in a single surgical procedure. A small residual opening was noted at the level of the incisive papilla in each dog; this was of no clinical consequence in this report. CLINICAL RELEVANCE: The von Langenbeck technique, using the simple closure modifications reported, was effective in closing both narrow and wide defects. Successful execution requires the complete elevation of each flap, which facilitates their tension-free advancement over the palatal cleft. Vertical mattress sutures evert the flap margins, allowing for direct collagen surface contact for proper healing. Placement of sutures in the rugal folds increases the tissue purchase to reduce the risk of suture cut-out. Fine interrupted sutures, placed between the vertical mattress sutures, maintains the proper alignment of the incisional margins. The author waits a minimum of 5 months before closing cleft palate defects, enabling the donor areas time to mature and improving their ability to retain sutures more effectively.

Mutation of the MYH3 gene causes recessive cleft palate in Limousine cattle.

BACKGROUND: The palate is a structure separating the oral and nasal cavities and its integrity is essential for feeding and breathing. The total or partial opening of the palate is called a cleft palate and is a common malformation in mammals with environmental or hereditary aetiologies. Generally, it compromises life expectancy in the absence of surgical repair. A new form of non-syndromic cleft palate arose recently in Limousine cattle, with animals referred to the French National Observatory of Bovine Abnormalities since 2012. Since the number of affected animals has increased steadily, this study was undertaken to identify the cause of this disease. RESULTS: Based on pedigree analysis, occurrence of cleft palate in Limousine cattle was concordant with an autosomal recessive mode of inheritance. Genotyping of 16 affected animals and homozygosity mapping led to the identification of a single disease-associated haplotype on Bos taurus chromosome (BTA)19. The genome of two affected animals was sequenced, and their sequences were compared to the ARS-UCD1.2 reference genome to identify variants. The likely causal variants were compared to the variant database of the 1000 bull genome project and two fully linked mutations in exon 24 of the MYH3 (myosin heavy chain) gene were detected: a 1-bp non-synonymous substitution (BTA19:g.29609623A>G) and a 11-bp frameshift deletion (BTA19:g.29609605-29609615del). These two mutations were specific to the Limousine breed, with an estimated allele frequency of 2.4% and are predicted to be deleterious. The frameshift leads to a premature termination codon. Accordingly, mRNA and protein analyses in muscles from wild-type and affected animals revealed a decrease in MYH3 expression in affected animals, probably due to mRNA decay, as well as an absence of the MYH3 protein in these animals. MYH3 is mostly expressed in muscles, including craniofacial muscles, during embryogenesis, and its absence may impair palate formation. CONCLUSIONS: We describe a new form of hereditary cleft palate in Limousine cattle. We identified two fully linked and deleterious mutations, ultimately leading to the loss-of-function of the MYH3 protein. The mutations were included on the Illumina EuroG10k v8 and EuroGMD v1 SNP chips and are used to set up a reliable eradication strategy in the French Limousine breed.

Management of Dental and Oral Developmental Conditions in Dogs and Cats.

Developmental dental and oral disorders are present in juvenile patients less than 12 months of age. The conditions are diverse ranging from cosmetic only to requiring advanced surgical intervention to alleviate pain and secondary complications. Clinical presentation, diagnosis, and appropriate treatment of dental abnormalities including abnormalities in the number, structure, size, and shape of teeth, as well as oral abnormalities including malocclusions, congenital cleft lip and palate, developmental abnormalities resulting in bony proliferation, and soft-tissue abnormalities of the lip and tongue are discussed throughout the article.

Clinical, tomographic, and postmortem aspects of a rare congenital Dicephalus Monauchenos Iniodymus in a Nelore calf produced in vitro from Brazil: case report / Aspectos clínicos, tomográficos e pós-morte de um raro Dicephalus Monauchenos Iniodymus congênito em um bezerro Nelore produzido in vitro no Brasil: relato de caso

The aim of this work was to report the occurrence of dicephalus iniodymus monauchenos in a Nellore newborn. A three-days old calf, from in vitro production, with duplication of the head and a history of cesarean birth was attended. On physical examination, the dicephalus, iniodymus and monauchenos, which were almost the same size and shape, had four eyes and four ears. Computed tomography showed the presence of two skulls fused with a common occipital foramen, two nasopharynxes, oropharynxes with the presence of a cleft lip and a cleft palate in the right head, which continued in a single esophagus and a single trachea. At necropsy, the presence of duplication of the cerebrum and cerebellum was observed, with union of the parts in the region of the trapezoid body of the brainstem and continued as a single spinal cord. This study characterizes the clinical, tomographic, and necropsy findings of a dicephalus Nelore neonate.(AU)

O objetivo deste trabalho foi relatar a ocorrência de Dicephalus Iniodymus Monauchenos em um neonato da raça Nelore de produção in vitro. Foi atendida uma fêmea bovina, de três dias de idade, com duplicação das cabeças e histórico de nascimento por meio de cesariana. No exame físico, observou-se a dicefalia, Iniodymus e Monauchenos, apresentando quatro olhos e quatro orelhas. Na tomografia computadorizada, constatou-se a presença de dois crânios fundidos com um forame occipital comum, duas nasofaringes, orofaringes com presença de lábio leporino e fenda palatina na cabeça direita, que continuavam em um único esôfago e em uma única traqueia. Na necropsia, observou-se a presença de duplicação do encéfalo e cerebelo, com união das partes na região do corpo trapezoide do tronco encefálico, que continuavam como uma única medula espinhal. Este estudo caracteriza os achados clínicos, tomográficos e de necropsia de um neonato Nelore dicefálico.(AU)

Facial malformations, including cleft lip and palate, in wild primates in Paraguay.

Nine individual Alouatta caraya and Sapajus cay displaying facial malformations were observed across three sites in Paraguay. Six had cleft lip (with or without cleft palate), and three had malformations of the lower lip. This is the first record of cleft lip and/or palate in the genus Alouatta.

Validation of a novel method for canine eruption assessment in unilateral cleft lip and palate patients.

OBJECTIVE: The aim of this study was to propose and validate a three-dimensional (3D) methodology for the assessment of canine eruption in patients born with unilateral cleft lip and palate (UCLP) following secondary alveolar bone graft (SABG). METHODS AND MATERIALS: A total of 10 patients (four females, six males; mean age: 8.8 years) with UCLP who underwent SABG were recruited. Pre- and 6-month post-operative cone-beam computed tomography (CBCT) was acquired for all patients. Post-operative data was registered onto pre-operative data utilizing voxel-based registration. Following superimposition, a segmentation process was applied to segment maxillary canine on both cleft and non-cleft side. Thereafter, translational and rotational changes in canine position were assessed for both cleft and non-cleft side by two observers. RESULTS: The intra-class correlation coefficient (ICC) indicated excellent reliability (≥0.90) with inter and intra-observer error of less than 0.05 mm. The overall ICC was found to be high for assessing both translational and rotational changes. The mean absolute inter- and intra-observer difference for translational and rotational changes was found to be less than 1 mm and 3°. CONCLUSION: The present method was found to be reliable proving to be clinically applicable for assessing maxillary canine eruption changes in both cleft and non-cleft bone.

Predictive factors for canine position in patients with unilateral cleft lip and palate.

OBJECTIVES: The aims were to compare cleft and non-cleft canine position, to find predictive factors for canine position and to assess surgically exposed canines. MATERIALS/METHODS: One hundred forty-eight individuals, born 1978-2005, with total unilateral cleft lip and palate (including Simonart's band <5 mm) treated in Gothenburg, were included. Canine angulation as well as vertical and horizontal position were assessed on panoramic radiographs (PAN) taken at the age of 10. Plausible predictive factors were registered from PAN, cast models and medical records. Data on spontaneous eruption or surgical exposure were available for 88 patients. Cleft- and non-cleft side was compared using paired t-test and Fisher's exact test. Multiple stepwise regression analysis and logistic regression analysis were used to detect possible predictors for cleft canine position. RESULTS: The cleft canine angulation was 29.3 ± 13.1 degrees (mean ± standard deviation) versus 7.6 ± 8.2 degrees on the non-cleft side (p < 0.001). Cleft canines were higher positioned and located closer to the midline compared to non-cleft canines (p < 0.001). Age for both hard palate closure and bone grafting, cleft lateral agenesis as well as transposition were associated with canine position. Cleft canines that required surgical exposure (28%) had an increased angulation and were higher positioned than spontaneously erupted canines (p < 0.001). LIMITATIONS: The shortcomings were the retrospective design and incomplete assessment of the buccal-palatal canine position on 2D images. CONCLUSIONS/IMPLICATIONS: With increased age for bone grafting, decreased age for hard palate closure and transposition, an association with abnormal canine position was found. A rigorous monitoring of cleft canine eruption is, therefore, advocated.

Mapping of the chicken cleft primary palate mutation on chromosome 11 and sequencing of the 4.9 Mb linked region.

An embryonic lethal mutation in chicken named cleft primary palate (cpp) is inherited in an autosomal recessive mode and results in a severely truncated upper beak. In this study, genotyping and sequencing techniques were employed to advance our genetic and genomic knowledge of the mutation's chromosomal location, candidate region and possible causative element using a congenic inbred line. Herein, the candidate region for the cpp developmental mutation was established as a ca. 5.1 Mb region of chicken chromosome 11 (GGA 11) through the use of a 600K Affymetrix SNP array. The SNPs identified from this array linked to cpp were used to genotype individuals from the congenic inbred line over several generations and thereby fine-map the causative region resulting in an approximately 200 kb size reduction. This candidate region (4.9 Mb) was sequenced via capture array in a cohort of 24 individuals, including carriers, mutants and their wild type (wt) siblings. Interestingly, the GGA 11 region for cpp encompasses the predicted centromere location and is thus unlikely to be highly disrupted by further recombination. Here we report on the variation unique to the cpp mutation, i.e. single-nucleotide variants and insertions or deletions. Although the candidate region contains several genes of interest with regard to the cpp phenotype, only one cpp-linked variant was predicted to have a significant physiological effect by causing a frameshift mutation in ESRP2, which has a role in tissue-specific splicing during development.

Incidence patterns of orofacial clefts in purebred dogs.

Cleft lip (CL), cleft palate (CP) and cleft lip and palate (CLP) are the most common types of orofacial clefts in dogs. Orofacial clefts in dogs are clinically relevant because of the associated morbidity and high newborn mortality rate and are of interest as comparative models of disease. However, the incidence of CL, CP and CLP has not been investigated in purebred dogs, and the financial impact on breeders is unknown. The aims of this study were to document the incidence patterns of CL, CP and CLP in different breeds of dogs, determine whether defect phenotype is associated with skull type, genetic cluster and geographic location, and estimate the financial impact in breeding programs in the United States by means of an anonymous online survey. A total of 228 orofacial clefts were reported among 7,429 puppies whelped in the 12 preceding months. Breeds in the mastiff/terrier genetic cluster and brachycephalic breeds were predisposed to orofacial clefts. Certain breeds in the ancient genetic cluster were at increased odds of orofacial clefts. Male purebred dogs were at increased odds of CPs. Results confirm that brachycephalic breeds are overrepresented among cases of orofacial clefts. Furthermore, geographic region appeared to be a relevant risk factor and orofacial clefts represented a considerable financial loss to breeders. Improved understanding of the epidemiology of orofacial clefts (frequency, causes, predictors and risk factors) may help in identifying ways to minimize their occurrence. Information gained may potentially help veterinarians and researchers to diagnose, treat and prevent orofacial clefts.

Correção de fenda palatina secundária traumática em cão - relato de caso / Correction cleft palate secondary traumatic in dog - case report

A fenda palatina é a comunicação entre a cavidade oral e a nasal através de um orifício no palato. Tem diversas etiologias, podendo ser congênita, traumática, por deficiência mineral ou por fatores hormonais. O diagnóstico é realizado por meio de exame físico da cavidade oral, e a correção cirúrgica é o tratamento de escolha. Em animais adultos, pode ser corrigida com o auxílio de retalho mucoperiosteal, apresentando bons resultados. Já em filhotes, a correção cirúrgica é mais complicada, com prognóstico menos favorável. Este trabalho relata o caso de um canino, fêmea, sem raça definida, adulta, com histórico de fenda palatina secundária, de origem traumática, no palato mole por ingestão de osso. Para a correção cirúrgica, primeiramente foi utilizada membrana biológica de pericárdio bovino, mas não se obteve êxito. O segundo procedimento foi realizado com retalho mucoperiosteal simples autólogo e, dois meses após o procedimento, já havia cicatrização completa. A técnica de retalho mucoperiosteal simples autólogo se mostrou eficaz no tratamento da fenda palatina, aliada aos cuidados adequados no pós-operatório.(AU)

The cleft palate is the communication between the oral and nasal cavity through an aperture in the palate, it's causes include an infinitude of factors: congenital, traumatic, mineral deficiency or hormonal. Examination of the oral cavity determines if the diagnosis and treatment is surgical. Correction in adult animals is performed with mucoperiosteal flap showing good results. However, surgical correction in puppies is more complicated with less favorable prognosis. This current work reports a case of an adult, female dog of undefined breed, with a history of secondary clef palate of traumatic origin in the soft palate due to bone ingestion. For correction, a biological membrane of bovine pericardium was used, but it was not successful, requiring a second surgical procedure performed with autologous simple mucoperiosteal flap. The last technique combined with adequate postoperative care was effective.(AU)

Levels of polycyclic aromatic hydrocarbons in umbilical cord and risk of orofacial clefts.

Polycyclic aromatic hydrocarbons (PAHs), which are ubiquitous in the environment, have been found to cause orofacial clefts (OFCs) in mouse model. However, evidence from the human study with markers of intrauterine exposure is absent. We explored the associations between the levels of sixteen PAHs in umbilical cord tissue and risk for OFCs using multivariable logistic models and Bayesian Kernel Machine Regression (BKMR). This case-control study included 89 OFC cases and 129 controls without congenital malformations. Concentrations of PAHs in umbilical cord tissue were detected using gas chromatography coupled to triple quadrupole tandem mass spectrometry. The median levels of ΣPAHs, Σlow molecular weight polycyclic aromatic hydrocarbons, and Σhigh molecular weight polycyclic aromatic hydrocarbons were all higher in cases of total OFCs and its subtypes than in controls, although the differences were not statistically significant. No statistical associations between levels of PAHs in umbilical cord tissue and risk for OFCs were observed in either multivariable logistic models or BKMR models. Maternal using a stove for heating and lower frequency of ventilation in the bedroom/living room, and consumptions of fresh green vegetables were positively correlated with levels of PAHs in umbilical cord. In conclusion, our results did not suggest that in utero exposure to PAHs were associated with the risk for OFCs, in estimating whether single effect of PAHs or joint effects of multiple PAHs.

Outcomes of surgical repair of congenital palatal defects in dogs.

OBJECTIVE To determine and identify variables associated with outcomes of surgical repair of congenital palatal defects in dogs. DESIGN Retrospective case series with nested observational study. ANIMALS 26 dogs that underwent surgical repair of congenital palatal defects at 2 veterinary teaching hospitals from 2007 to 2016. PROCEDURES Data were collected from medical records regarding dog age and body weight at the time of surgical defect repair, prior surgical history, skull type (brachycephalic, mesocephalic, or dolichocephalic), surgical technique used for defect repair, and defect severity. Functional outcome as well as frequency and location of oronasal fistula (ONF) formation were recorded. These outcomes were compared among various groups. RESULTS Surgical defect repair achieved functional success in 22 of the 26 (85%) dogs. An ONF formed after initial repair in 13 (50%) dogs, and the most common location was the hard palate. Hard palate ONF formation was more common in dogs > 8 months of age at the time of initial repair; ONF at the junction between the hard and soft palates was more common in dogs > 8 months of age at the time of initial repair and in dogs with a history of failed surgical repair. An unsuccessful functional outcome was more common in dogs weighing < 1 kg (2.2 lb) at the time of initial repair. CONCLUSIONS AND CLINICAL RELEVANCE Patient age, patient size, and defect characteristics should be taken into consideration when planning and assessing prognoses for surgical repair of congenital palatal defects in dogs.

Computed tomographic evaluation of cleft palate in one-day-old puppies.

BACKGROUND: Cleft palate is a birth defect characterized by a lack of fusion between structures forming the palate. Causes include a multitude of factors, both genetic and environmental. Computed tomography (CT) is widely used to evaluate morphological features and diagnose head disorders in adult dogs. However, there is less data about its use in neonatal dogs. The purpose of this study was to perform CT evaluation of palatal defects in one-day-old puppies and to present a novel approach of 3D modeling in terms of cleft palate assessment. RESULTS: Macroscopic and CT examinations were performed in 23 stillborn or euthanized purebred newborn puppies. On the basis of CT data, a 3D model was prepared and the cleft surface area was then calculated. A multi-stage approach, which utilised software such as 3D Slicer and Blender, was applied. Palatal defects were found in ten dogs, of which five had cleft palate, three had bilateral cleft lip and palate, one had a unilateral cleft lip and palate and one had a unilateral cleft lip. The surface area of the clefts ranged from 31 to 213 mm2, which made up respectfully 11 to 63% of the total surface area of the palate. No abnormalities were found in thirteen dogs and they made up the control group. CONCLUSIONS: Computed tomography and 3D modeling were very effective in evaluation of palatal disorders in newborn dogs. 3D models adapted to the natural curvature of the palate were created and more precise data was obtained. Morphological characteristics, CT findings and advanced image analysis of cleft palate in neonates obtained from these models increase the knowledge about this malformation in dogs.

Transcriptome profiling reveals candidate cleft palate-related genes in cultured Chinese sturgeons (Acipenser sinensis).

The Chinese sturgeon (Acipenser sinensis) is an anadromous fish distributed in the Yangtze River and the East China Sea. In this study, we report the novel finding of cleft palates in Chinese sturgeons derived from artificial fertilization. To explore the genetic basis of palate malformation in A. sinensis, Illumina RNA-seq technology was used to analyze the transcriptome data of farmed Chinese sturgeons with normal palates and cleft-palates. Raw reads were obtained and assembled into 808,612 unigenes, with an average length of 509.33 bp and an N50 of 574 bp. Sequence similarity analyses against four public databases (Nr, UniProt, KEGG, and COGs) found 158,642 unigenes that could be annotated. GABAergic synapses and TGF-ß signal pathways were the two most enriched pathways with high Rich Factors in the analyses of differentially expressed genes. In these two signal pathways, six genes (GABRA4, GS, GNS, S6K, PITX2, and BMP8) were found as candidate cleft-palate genes in Chinese sturgeon. These findings contribute to our understanding of cleft palate genetics in sturgeon, while simultaneously adding to our knowledge about craniofacial development.

A numerical classification system for cleft lip and palate in the dog.

An easy-to-use classification that enables an accurate record of canine cleft lip and palate is fundamental for effective communication between professionals and researchers and optimal use of published information. Here we present how a classification system for human cleft lip and palate can be used to register spontaneous cases in dogs, highlighting its advantages. This system is based on four topographic areas with a numerical representation of the severity of the cleft in each area. The use of spontaneous cases has the advantage of providing clefts that are naturally similar to their human counterparts for surgical, genetic and genomic studies and, furthermore, will reduce the need for experimental models of this condition.

Morphological evaluation of clefts of the lip, palate, or both in dogs.

OBJECTIVE To systematically characterize the morphology of cleft lip, cleft palate, and cleft lip and palate in dogs. ANIMALS 32 client-owned dogs with clefts of the lip (n = 5), palate (23), or both (4) that had undergone a CT or cone-beam CT scan of the head prior to any surgical procedures involving the oral cavity or face. PROCEDURES Dog signalment and skull type were recorded. The anatomic form of each defect was characterized by use of a widely used human oral-cleft classification system on the basis of CT findings and clinical images. Other defect morphological features, including shape, relative size, facial symmetry, and vomer involvement, were also recorded. RESULTS 9 anatomic forms of cleft were identified. Two anatomic forms were identified in the 23 dogs with cleft palate, in which differences in defect shape and size as well as vomer abnormalities were also evident. Seven anatomic forms were observed in 9 dogs with cleft lip or cleft lip and palate, and most of these dogs had incisive bone abnormalities and facial asymmetry. CONCLUSIONS AND CLINICAL RELEVANCE The morphological features of congenitally acquired cleft lip, cleft palate, and cleft lip and palate were complex and varied among dogs. The features identified here may be useful for surgical planning, developing of clinical coding schemes, or informing genetic, embryological, or clinical research into birth defects in dogs and other species.