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.

Pilot study of factors contributing to canine impaction after secondary alveolar bone grafting in unilateral cleft lip and palate patients.

Alveolar bone grafting (ABG) is broadly performed for cleft lip and palate patients. The rate of canine impaction post-ABG is much higher than the prevalence of canine impaction in non-cleft patients. This pilot study was designed to investigate factors involved in canine eruption failure after ABG and to predict the possibility of canine impaction in unilateral cleft lip and palate (UCLP) patients. This retrospective observational study examined 45 patients with UCLP (mean age 7.9 years) classified into an impacted group (n = 9) and a spontaneously erupted group (n = 36). From 3D images, we measured lateral incisor presence or absence, lateral incisor position on the cleft side, canine position, movement change, cleft volume, and canine and first premolar overlap-area. Multivariate logistic regression analysis using independent variables indicated significant differences in results, selecting highly relevant items. Multivariate analysis indicated a significant association between the overlap-area between the canine and the first premolar at pre-ABG (p = 0.038) and the distance between the cleft side cusp tips of canine and the lateral cleft margin of pre-ABG (p = 0.005). Results suggest that canine impaction is predictable at an early stage in pre-ABG and show the possibility of comprehensive diagnosis of canine impaction using computed tomography.

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.

Prenatal diagnosis of foetal hydrocephalus and suspected X-linked recessive inheritance of cleft lip in a Chihuahua.

A 3.5-year-old, 2.9 kg, multiparous Chihuahua presented with abdominal distension; pregnancy was diagnosed. On Day 7 before parturition, prenatal sonograms showed anechoic bilateral dilated cerebral lateral ventricles, suggesting fluid-filled regions (ventriculomegaly) in one foetus. A Caesarean section was performed and the male newborn had an abnormally enlarged dome-shaped head and a cleft lip, and died 6 days after birth. According to the family pedigree, the X-linked recessive inheritance of an orofacial cleft from the unaffected mother was suggested. This report clearly demonstrates that canine foetal ventriculomegaly (hydrocephalus) can be diagnosed in utero. For dog breeds predisposed to congenital ventriculomegaly, early detection is important for the prediction of perinatal survival and adequate supportive care can be applied at delivery.

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.

Mutations of GADD45G in rabbits cause cleft lip by the disorder of proliferation, apoptosis and epithelial-mesenchymal transition (EMT).

The cleft lip with or without cleft palate (CL/P) is one of the most common congenital defects in humans. Genome-wide association studies (GWAS) have been widely used for identifying candidate genes, and different genes or chromosomal regions have shown strong evidence for the presence of causal genes in CL/P. To date, two independent GWAS have identified GADD45G as influencing risk for CL/P. However, there is no animal model evidence about GADD45G related to CL/P. Here, we reported the generation of a novel GADD45G mutated rabbit model by CRISPR/Cas9 and CRISPR-based BE4-Gam systems. The homozygous (GADD45G-/-) while not heterozygous (GADD45G+/-) pups died after birth due to severe craniofacial defects of unilateral or bilateral cleft lip (CL). Moreover, the disorder of proliferation, apoptosis and epithelial-mesenchymal transition (EMT) were also determined in the medial and lateral nasal processes (MNP and LNP) of the embryonic day 13 (E13) GADD45G-/- rabbits, which compared with the normal wild type (WT) rabbits. Thus, our study confirmed for the first time that loss of GADD45G lead to CL at the animal level and provided new insights into the crucial role of GADD45G for upper lip formation and fusion.

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.

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.

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.

Breeding experiments and genome-wide association analysis elucidate two genetically different forms of non-syndromic congenital cleft lip and jaw in Vorderwald × Montbéliarde cattle.

Non-syndromic congenital cleft lip and jaw (CLJ) is a condition reported in Vorderwald × Montbéliarde cattle. The objective of the present study was to perform a genome-wide association study (GWAS) for 10 CLJ-affected and 50 unaffected Vorderwald × Montbéliarde cattle using the bovine Illumina high density bead chip to identify loci for this condition. Phenotypic classification of CLJ was based on a detailed recording of orofacial structures using computed tomography. A breeding experiment among CLJ-affected Vorderwald × Montbéliarde cattle and CLJ-affected Vorderwald × Montbéliarde cattle with unaffected Holsteins confirmed recessive inheritance and different loci for bilateral or left-sided versus right-sided CLJ. The GWAS for the five cases with right-sided CLJ gave a genome-wide signal on bovine chromosome (BTA) 29 at 16 Mb. For the four left-sided and one bilateral CLJ case, a genome-wide significant association was identified on BTA4 at 32 Mb. Two different loci are very likely to be involved in CLJ in Vorderwald × Montbéliarde cattle because experimental matings among affected cows and bulls with different types of CLJ did not result in CLJ-affected progeny, and in addition, two different loci were also found through GWAS and mapped on two different bovine chromosomes. Validation in 346 Vorderwald × Montbéliarde cattle for the highly associated SNPs on BTA4 and 29 gave ratios of 33/346 (0.095, BTA4) and 6/346 (0.017, BTA29) homozygous mutant genotypes. Further studies should elucidate the responsible mutations underlying the different types of CLJ in Vorderwald × Montbéliarde cattle.

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.

Reconstruction of Congenital Nose, Cleft Primary Palate, and Lip Disorders.

Clefts of the primary palate in the dog are uncommon, and their repair can be challenging. The aims of this article are to provide information regarding pathogenesis and convey practical information for the repair of these defects.

Canine pediatric dentistry.

The oral examination is an important part of the physical examination of every patient. In neonate and adolescent dogs, it is important to inspect the oral cavity for congenital and acquired dental and oral pathology. This article reviews the more common pediatric and juvenile dental anomalies that affect dogs in order to provide a resource for the basic understanding of the oral cavity in these patients.

Oral folic acid supplementation decreases palate and/or lip cleft occurrence in Pug and Chihuahua puppies and elevates folic acid blood levels in pregnant bitches.

The aim of this study was to compare the frequency of the occurrence of lip and/or palate cleft (CL/CP) in new-borns of two breeds, Pugs and Chihuahuas, and to measure the folic acid blood levels in bitches during gestations both with and without folic acid oral supplementation. Bitches of 13 Pugs and 17 Chihuahuas with CL/CP cases were used in the study. In trial 1, the animals of the experimental group (n=25) were given additional folic acid from the onset of heat till the 40th day of gestation. The females of the control group (n=12) were fed a traditional diet. From all the animals blood was collected at the onset of heat, 14 days later and on the 30th day of the gestation to estimate folic acid concentration. In trial 2, the prevalence of CP/CL cases in litters from pregnancies before and after supplementation was compared. The percentage of puppies with CL/CP after supplementation decreased in both Pugs and Chihuahua puppies (10.86% and 15.78% vs. 4.76% and 4.8% respectively). On Day 0, the concentrations of folic acid were at a low physiological level (around 8 ng/ml) in all the animals. In bitches of the experimental group the blood level of folic acid on day 14th and 30th of the treatment showed an increase in both breeds (13.65 +/- 4.27 ng/ml in Pugs, 10.79 +/- 2.84 ng/ml in Chihuahuas, and 14.94 +/- 3.22 ng/ml in Pugs, 12.95 +/- 3.58 in Chihuahuas, respectively) while in the control group, this level decreased with time of gestation both in Pugs and in Chihuahuas (around 6 ng/ml). Folic acid supplementation seems to be a simple, effective preventive method to reduce the risk of CL/CP, especially in the predisposed breeds.

Right-sided cleft lip and jaw in a family of Vorderwald × Montbéliarde cattle.

A congenital unilateral cleft lip and jaw in association with campylognathia to the opposite side was identified in a family of Vorderwald×Montbéliarde cattle. Clinical examination, radiography and computed tomography revealed similar types and degrees of orofacial abnormality in three affected animals from different farms. Digital radiographs and computed tomography demonstrated absence of the rostral segment of the incisive bone in association with sigmoid curvature of the rostral lower jaw and campylognathia to the left side. All three affected animals could be traced back to a common ancestor, a Montbéliarde bull, who had sons and grandsons used for in-crossing in Vorderwald cattle. The affected animals were inbred on Montbéliarde sires, with inbreeding coefficients of 0.39% in one calf and 6.25% in two calves. Pedigree analysis supported the hypothesis of an autosomal recessive mode of inheritance.

Cleft lip and palate associated with other malformations in a neotropical primate (Saimiri ustus).

Cleft lip (with or without cleft palate) has been documented in several species of nonhuman primates, which in general are susceptible at similar doses and stages of gestation to the same teratogens as humans. Cleft lip can be unilateral or bilateral, isolated, syndromic, familial, or genetic. Here we report the first case of syndromic cleft lip and palate in a male bare-eared squirrel monkey (Saimiri ustus). Associated with the orofacial clefts, the monkey manifested absence of bones, malformation of vertebrae L3, only 4 fingers in each hand, and shortening of tendons leading to inflection of the hands and fingers. Previous reports describing cleft lip and palate in other squirrel monkeys (Saimiri sciureus) in other breeding units have suggested consanguineous mating as a possible cause. Although the etiology in the case we present is unknown, we discuss factors associated with orofacial clefts in humans and various nonhuman primates.