Canine DVL2 variant contributes to brachycephalic phenotype and caudal vertebral anomalies.

A frameshift deletion variant in the Wnt pathway gene dishevelled 2 (DVL2) is associated with a truncated, kinked tail ("screw tail") in English Bulldogs, French Bulldogs and Boston Terriers. These breeds are also characterized by distinctive morphological traits, including a wide head, flat face and short-limbed dwarfism, which are characteristic of Robinow syndrome in humans, caused by defects in genes such as DVL1 and DVL3. Based on these phenotypic and genetic similarities, it has previously been hypothesized that the canine DVL2 variant results in a syndromic phenotype called the Robinow-like syndrome. In our study, we investigated the distribution of the DVL2 variant in 1954 dogs from 15 breeds, identifying breeds with allele variation and enabling the dissection of the genotype-phenotype correlation for the first time. With CT examinations in American Staffordshire Terriers, we confirmed that the DVL2 allele is associated with caudal vertebral malformations and a brachycephalic phenotype. We also hypothesize that the variant may be linked to additional health conditions, including brachycephalic obstructive airway syndrome and congenital heart defects. Altogether, our study strengthens the role of DVL2 as one of the contributors to the "bulldog type" morphology and features on the spectrum of human Robinow syndrome.

Whole genome variant association across 100 dogs identifies a frame shift mutation in DISHEVELLED 2 which contributes to Robinow-like syndrome in Bulldogs and related screw tail dog breeds.

Domestic dog breeds exhibit remarkable morphological variations that result from centuries of artificial selection and breeding. Identifying the genetic changes that contribute to these variations could provide critical insights into the molecular basis of tissue and organismal morphogenesis. Bulldogs, French Bulldogs and Boston Terriers share many morphological and disease-predisposition traits, including brachycephalic skull morphology, widely set eyes and short stature. Unlike other brachycephalic dogs, these breeds also exhibit vertebral malformations that result in a truncated, kinked tail (screw tail). Whole genome sequencing of 100 dogs from 21 breeds identified 12.4 million bi-allelic variants that met inclusion criteria. Whole Genome Association of these variants with the breed defining phenotype of screw tail was performed using 10 cases and 84 controls and identified a frameshift mutation in the WNT pathway gene DISHEVELLED 2 (DVL2) (Chr5: 32195043_32195044del, p = 4.37 X 10-37) as the most strongly associated variant in the canine genome. This DVL2 variant was fixed in Bulldogs and French Bulldogs and had a high allele frequency (0.94) in Boston Terriers. The DVL2 variant segregated with thoracic and caudal vertebral column malformations in a recessive manner with incomplete and variable penetrance for thoracic vertebral malformations between different breeds. Importantly, analogous frameshift mutations in the human DVL1 and DVL3 genes cause Robinow syndrome, a congenital disorder characterized by similar craniofacial, limb and vertebral malformations. Analysis of the canine DVL2 variant protein showed that its ability to undergo WNT-induced phosphorylation is reduced, suggesting that altered WNT signaling may contribute to the Robinow-like syndrome in the screwtail breeds.

Congenital Urethrovaginal Fistula with Blind-Ending Vagina in a Female Pseudohermaphrodite Dog with Urinary Incontinence.

An 8 mo old male Doberman pinscher was referred for investigation of persistent urinary incontinence. Physical examination revealed urine leakage and abnormal external genitalia. A computed tomography scan identified a large fluid-filled cavity extending from the caudoventral abdomen displacing the colon and urinary bladder. No retained testicles were identified. A retrograde urethrogram study found a linear communication, cranial to the pubic brim between the urethra to the fluid-filled cavity (fistula). Exploratory celiotomy was performed, and an entire female reproductive tract with a blind-ending vagina and a urethrovaginal fistula was found. En bloc gonad hysterectomy was performed, the fistula was transected, and a careful urethral reconstruction was performed. The urinary incontinence resolved immediately after surgery, and no complications were reported. Mild urinary incontinence recurred 4 days following patient discharge, and a urine bacterial culture was positive for Klebsiella spp. An antibiotic course was prescribed, and the incontinence fully resolved. Congenital urogenital abnormalities should always be considered in young animals presenting with urinary incontinence. Here, a young female pseudohermaphrodite dog with a naturally occurring congenital urethrovaginal fistula is described. Exploratory surgery was required for definitive diagnosis and surgical intervention yielded a good medium-term outcome with resolution of clinical signs.

Segmental uterine aplasia and ipsilateral renal agenesis in a ragdoll cat.

During a routine ovariohysterectomy on a 5-month-old ragdoll cat, right-sided segmental uterine aplasia and ipsilateral renal agenesis were discovered. The diagnosis was confirmed with histopathology. This condition is congenital and is a result of a failure of embryonic development of the paramesonephric ducts. Uterine aplasia and renal agenesis is a rare finding in cats but the prevalence in the ragdoll breed appears to be higher than in the general cat population.

Aplasie utérine segmentaire et agénésie rénale ipsilatérale chez un chat ragdoll. Lors d'une ovario-hystérectomie de routine chez une chatte ragdoll âgée de 5 mois, une aplasie utérine segmentaire du côté droit et une agénésie rénale ipsilatérale furent découvertes. Le diagnostic fut confirmé par histopathologie. Cette condition est congénitale et est le résultat d'une défaillance de développement embryonnaire des conduits paramésonéphriques. L'aplasie utérine et l'agénésie rénale sont des trouvailles rares chez les chats mais la prévalence chez la race ragdoll semble être plus élevée que dans la population générale de chats.(Traduit par Dr Serge Messier).

Complex malformations of the urogenital tract in a female dog: Gartner duct cyst, ipsilateral renal agenesis, and ipsilateral hydrometra.

A 10-month-old female toy poodle was referred to the University of Tokyo Veterinary Medical Center with a urogenital anomaly found during sterilization. An exploratory laparotomy revealed a cyst adhering to the cervix and a unilateral renal agenesis. Histopathology and immunohistochemical analysis of the cyst was consistent with remnants of the Wolffian duct or a Gartner duct cyst. This is a rare case of a canine Gartner duct cyst with renal agenesis and uterine anomaly. We discuss the similarity of this case to that of humans and introduce a classification in the literature for these complex urogenital malformations for further clinical research into the precise diagnosis and appropriate surgical planning.

Ovarian dysgenesis in an alpaca with a minute chromosome 36.

A 4-year-old female alpaca (Lama pacos [LPA]) was presented to the Oregon State Veterinary Teaching Hospital for failure to display receptive behavior to males. Although no abnormalities were found on physical examination, transrectal ultrasonographic examination of the reproductive tract revealed uterine hypoplasia and ovarian dysgenesis. Cytogenetic analysis demonstrated a normal female 74,XX karyotype with 1 exceptionally small (minute) homologue of autosome LPA36. Chromosome analysis by Giemsa staining and DAPI- and C-banding revealed that the minute LPA36 was submetacentric, AT-rich, and largely heterochromatic. Because of the small size and lack of molecular markers, it was not possible to identify the origin of the minute. There is a need to improve molecular cytogenetic tools to further study the phenomenon of this minute chromosome and its relation to female reproduction in alpacas and llamas.

Unilateral segmental uterine horn hypoplasia with fallopian tube aplasia in a guinea pig (Caviaporcellus).

A 2-year-3-month-old female guinea pig (Cavia porcellus) was referred for lethargy, weight gain and severe abdominal pain. Ultrasound examination revealed thickening and enlargement of the left uterine horn and an unremarkable right uterine horn. The animal died during ovariohysterectomy due to respiratory and cardiac arrest. Necropsy revealed unilateral segmental uterine horn hypoplasia and aplasia of the fallopian tube of the corresponding side. This is the first report of a congenital uterine malformation in the guinea pig and we describe the clinical and pathological presentation of segmental uterine horn hypoplasia and fallopian tube aplasia. Congenital uterine malformations are rare in guinea pigs but should be considered as differential diagnoses for the more common acquired uteropathies.

Environmental pollutants and diseases of sexual development in humans and wildlife in South Africa: harbingers of impact on overall health?

This study deals with disorders of sexual development in humans, wildlife and animals in an urban nature reserve (RNR) and a currently DDT-sprayed malarial area. High levels of oestrogenic chemical residues in water, sediment and tissue; skewed sex ratios; reduced biodiversity; gonadal malformations in sharptooth catfish and freshwater snails; intersex in catfish; and impaired spermatogenesis in catfish and striped mouse are of serious concern in the RNR. Persistent eggshell thinning in African darter eggs, intersex in male Mozambican tilapia, follicular atresia in females and impaired spermatogenesis in males following laboratory exposure of parent fish to environmentally relevant DDT and DDE concentrations, and abnormalities in freshwater snails were found in the DDT-sprayed area. Human studies related to DDT exposure indicated impaired semen quality, a weak association with sperm chromatin defects and higher risks for external urogenital birth defects in those who were born to mothers whose houses were sprayed and those who were homemakers (stay at home mother) instead of being employed. These findings indicate that diseases of sexual development occurred in both human and wildlife populations exposed to environmental endocrine disruptor chemicals in South Africa. The chemical mixtures, possibly related to disorders of sexual differentiation (DSD), were very different between the two. However, DSD occurred concurrently in the malarial area, possibly indicating that humans and wildlife shared exposures. Moreover, it emphasizes the importance of suspecting disease in the other when disease is found in either human or wildlife populations.

An unusual case of urinary incontinence in an intersex West Highland white terrier.

A 5-year-old neutered female West Highland white terrier dog was presented with a history of congenital urinary incontinence that had become refractory to medical management. Complex urogenital anomalies including urethrovestibular and vestibuloperineal fistulae with low vulvar position along with a penoclitoris were present. Vaginectomy with perineal urethral reconstruction resolved the incontinence.

Cas inusité d'incontinence urinaire chez un terrier blanc West Highland intersexué. Une chienne Terrier blanc West Highland stérilisée âgé de 5 ans a été présentée avec une anamnèse d'incontinence urinaire congénitale qui est devenue réfractaire à la gestion médicale. Des anomalies urogénitales complexes, incluant des fistules urétrovestibulaires et vestibulopérinéales avec une position vulvaire basse et un pénoclitoris, étaient présentes. Une vaginectomie avec une reconstruction de l'urètre périnéale a réglé l'incontinence.(Traduit par Isabelle Vallières).

Developmental uterine anomalies in cats and dogs undergoing elective ovariohysterectomy.

OBJECTIVE: To describe the characteristics and frequency of gross uterine anomalies in cats and dogs undergoing elective ovariohysterectomy. DESIGN: Prospective and retrospective case series. ANIMALS: 53,258 cats and 32,660 dogs undergoing elective ovariohysterectomy at 26 clinics in the United States and Canada during 2007. PROCEDURES: Clinics prospectively reported gross anomalies and submitted tissues from abnormal reproductive tracts identified during surgery. Records from a feral cat spay-neuter clinic were evaluated retrospectively. RESULTS: Suspected congenital anomalies of the uterus were identified in 0.09% (49/53,258) of female cats and 0.05% (15/32,660) of female dogs. Uterine anomalies identified included unicornuate uterus (33 cats and 11 dogs), segmental agenesis of 1 uterine horn (15 cats and 3 dogs), and uterine horn hypoplasia (1 cat and 1 dog). Ipsilateral renal agenesis was present in 29.4% (10/34) of cats and 50.0% (6/12) of dogs with uterine anomalies in which kidneys were evaluated. Mummified ectopic fetuses were identified in 4 cats with uterine anomalies. Both ovaries and both uterine tubes were present in most animals with uterine anomalies. CONCLUSIONS AND CLINICAL RELEVANCE: Urogenital anomalies were twice as common in cats as in dogs. Identification of uterine developmental anomalies in dogs and cats should trigger evaluation of both kidneys and both ovaries because ipsilateral renal agenesis is common, but both ovaries are likely to be present and should be removed during ovariohysterectomy.

Genital abnormalities associated to lack of uterine adenogenesis or endometrial gland dysgenesis of female dromedary camels (Camelus dromedarius).

Background: The developmental disruption of the müllerian duct and the endometrial dynamic can generate genital lesions that could contribute to infertility. Aim: This paper discusses two cases of genital conditions associated to endometrial gland pathologies in nulliparous female camels. Methods: Macroscopic examinations and histopathological description were performed on congenital and acquired genital abnormalities with endometrial gland anomalies. Results: The first case is endometrial gland agenesis associated to unilateral uterine aplasia, and the second case is endometrial gland dysgenesis associated to metritis. The prevalence of each case is estimated to be 0.6%. The most specific microscopic features associated to the endometrial gland agenesis were the presence of endometrial stromal proliferation and homogenous hyalinization of the myometrium. The acute metritis was associated to endometrial-activated stroma with focal infiltration with inflammatory cells on the endometrium and myometrium and the spontaneous endometrial gland dysgenesis. Conclusion: This study reveals the importance of congenital abnormalities during the routine reproductive examination of peripubertal animals, as well as the association of histopathological complementary examination for the research functional and inflammatory anomalies of the uterus. Genetic screening of breeders would be very important in the search for genetic risk factors associated with these congenital pathologies, which can be disseminated by reproductive biotechnologies.

Multiple urogenital abnormalities in a Persian cat.

A 1.5-year-old female Persian cat was presented for inappetence and azotemia. Ultrasonography and urography revealed multiple abnormalities involving the genitourinary tract, including agenesis of the right kidney and ureter. Gross examination of the abnormal uterus revealed segmental aplasia of right caudal uterine horn causing cranial distension with fluid, a normal left uterine horn, and both normal ovaries. Microscopically, endometrial glands of the right uterine horn were markedly decreased in number. The right uterine horn was hemorrhagic suggesting estrus. This is the first report of this combination of urinary and uterus abnormalities in the veterinary literature.

A complex malformation in a pig: case report and review of the literature.

Congenital defects like myofibrillar dysplasia (splayleg), umbilical and inguinal hernias, cryptorchism, intersexes, and anal atresia occur relatively frequently in swine. On the other hand, some developmental anomalies like double monsters are very rare. The present paper reports a rare case of a congenital complex malformation including polymelia, duplicitas coli partialis et recti, atresia ani et fistula rectogenitalis, duplicitas corpori uteri, cervicis, vaginae et vulvae and duplicitas vesicae, urethrae et renalis. A plausible interpretation concerning the etiology is that the anomalies arose from unequal partial twinning. The pig has been healthy and inconspicuous. Although no anus was formed defecation took place via a fistula to one of the vaginas. Posture and behaviour of the pig were normal. Cytogenetic analysis of blood lymphocytes revealed no numerical or gross structural anomalies. There have been no further piglets with developmental disorders in the same litter, in a second litter of the same parents and in other twelve litters by the same boar.

Urogenital anomalies and urinary incontinence in an English Cocker Spaniel dog with XX sex reversal.

A 3-year-old dog weighing 8 kg was referred with a disorder of sexual development and persistent urinary incontinence before and after gonadohysterectomy performed at a local animal hospital. Histopathological examination disclosed hypoplasia of the testes, epididymis, pampiniform plexus, and uterus. On ultrasonography, an anomalous structure containing anechoic fluid was identified in the region dorsal to the urinary bladder. An anomalous communication between the proximal urethra and the remnant uterus and vagina was found on retrograde urethrography under fluoroscopy. Reflux of contrast medium into the anomalous structure, suspected to be the uterus and cranial vagina, from the urethra was detected. Computed tomography identified the anomalous structure between the rectum and urethra. The anomalous structure was removed via laparotomy and the urinary incontinence resolved. The diagnosis of XX sex reversal with a developmental anomaly of the genitourinary tract was made on the basis of laparotomy findings and cytogenetic and SRY gene analyses.

Incomplete caudal duplication in a puppy: gross and radiological observations.

Caudal duplication is a rare type of conjoined twinning. The aim of this case report is to describe a case of caudal duplication in a male crossbreed puppy. The puppy was macroscopically and radiographically examined after death. External features included a supernumerary limb projecting from the perineum, complete lack of tail, anal atresia, double penis and absence of scrotal sacs. Internal examination showed anomalies involving the intestine and the urinary system. At x-ray examination, the supernumerary limb showed features similar to that of the normal right hindlimb but showed absence of fibula and tibia and presence of three metatarsi and phalanges. The authors discuss the pathogenic mechanisms of this condition, infrequently reported in veterinary practice, pointing out the importance of embryonic duplications commonly associated with dystocia.

Diphallia in a Mixed-Breed Puppy: Case Report.

An 8 mo old intact male mixed-breed dog presented for diphallia with paraphimosis of the nonfunctional, accessory penis. Bloodwork, an abdominal ultrasound, and a positive contrast retrograde urethrogram were performed and revealed no other structural abnormalities. Surgical excision of the accessory penis was elected. This is one of three reported cases of diphallia in the dog in the English literature, but this is the only case in which no other congenital abnormalities were identified. The authors also review diphallia in both the veterinary and human literature.

Proximal ureteral ectopia causing hydronephrosis in a kitten.

A 2-month-old, female cat was presented for abdomen dilation. The patient was undernourished, and severe left hydronephrosis was diagnosed after clinical, ultrasonographical and radiographical examination. Although pyelography was performed in order to visualise the ureteral course, surgery was necessary to reach a final aetiological diagnosis and treatment. At gross examination, the left ureter crossed the renal capsula at the level of the caudal renal pole, and the subcapsular ureteral segment was markedly dilated. Distal to the renal capsula, the left ureter was very thin when compared to the right. The parenchyma of the left kidney, as suggested by ultrasonographical evaluation, was extremely reduced in thickness. An ureteronephrectomy was performed. Histopathological evaluation revealed glomerular sclerosis and diffuse parenchymal fibrosis. Severe hydronephrosis derived from an altered renal pelvic anatomy and abnormal ureteral course determining functional stenosis. Diagnosis of congenital anomaly before development of complications such as hydronephrosis could have allowed a surgical renal capsulectomy and obstruction relief. To the author's knowledge, this is the first report of severe hydronephrosis associated to altered renal pelvic anatomy and proximal ureteral ectopia in cat.

Urinary Incontinence in Juvenile Female Soft-Coated Wheaten Terriers: Hospital Prevalence and Anatomic Urogenital Anomalies.

Urinary incontinence in juvenile female dogs is often associated with urogenital anatomic anomalies. Study objectives include: (1) determine hospital prevalence of urinary incontinence in juvenile female soft-coated wheaten terriers (SCWTs) compared to other affected dogs; (2) characterize anatomic anomalies affecting urinary incontinent juvenile female SCWTs utilizing uroendoscopy; and (3) compare incidence of ectopic ureters, paramesonephric remnants, and short urethras in juvenile female urinary incontinent SCWTs to other juvenile female dogs with urinary incontinence. We hypothesize juvenile SCWTs have an increased prevalence of urinary incontinence and an increased incidence of ectopic ureters, paramesonephric remnants, and short urethras compared to non-SCWTs with urinary incontinence within our hospital population. Medical records of female dogs 6 mo of age and younger with clinical signs of urinary incontinence and video uroendoscopic evaluation presenting to The Ohio State University Veterinary Medical Center from January 2000 to December 2011 were reviewed. Twelve juvenile SCWTs and 107 juvenile non-SCWTs met the inclusion criteria. Juvenile SCWTs were found to have an increased hospital prevalence of urinary incontinence compared to other affected breeds. Observed anomalies in SCWTs include: ectopic ureters, shortened urethras, paramesonephric remnants, and bifid vaginas. This information will help guide veterinarians in recognizing a breed-related disorder of the lower urogenital tract in SCWTs.

Abattoir survey of congenital reproductive abnormalities in ewes.

A survey of abnormalities of the reproductive tract of female sheep was undertaken at two abattoirs in the south west of England over a period of 12 months. During the survey, 9970 reproductive tracts from cull ewes and 23,536 tracts from nulliparous sheep (prime lambs and hoggets) were examined. A total of 655 (6.57 per cent) ewes and 459 (1.95 per cent) nulliparous sheep had abnormalities of the reproductive tract. Of these, congenital abnormalities of the paramesonephric ducts accounted for 2.4 per cent of the ewes and 7.4 per cent of the nulliparous sheep, congenital abnormalities of the ovaries accounted for 2.6 per cent of the ewes and 7.4 per cent of the nulliparous sheep and cystic structures that were considered to have been of congenital origin accounted for 27.2 per cent of the ewes and 52.7 per cent of the nulliparous sheep. The most common lesion was paraovarian cysts (26.6 per cent of ewes and 39.0 per cent of nulliparous sheep), but few of these appeared to have affected the sheep's reproductive function. Several specific conditions were recorded, including some described for the first time in sheep. Uterus unicornis occurred in 20 sheep and other forms of segmental aplasia of parts of the paramesonephric ducts occurred in a further 13 animals. Uterus didelphys occurred in six sheep, and 11 animals were intersex. Intersex sheep had vestigial structures that were derived from the paramesonephric ducts, hypoplastic or masculinised gonads and some had masculinised external genitalia. Ovarian hypoplasia occurred in 34 sheep, and in a further 12 mainly nulliparous animals, the ovaries were fused. Sixty nulliparous animals and two ewes had hydatids of Morgagni.

Multiple congenital genitourinary anomalies in a polled goat.

A 1-day-old, Toggenburg/Nubian crossbred goat of polled parentage was referred for necropsy because of a large (diameter, 5 cm) bladder-like mass protruding from the perineal midline and difficult urination. Differential diagnoses included cutaneous cyst, ectopic urinary bladder, and urethral diverticulum/dilatation. Several genitourinary aberrations were noted. A second, smaller (diameter, 1 cm), more distal cystic structure was adjacent to an ambiguous prepuce. Testicles were discovered within a constricted, subcutaneous space near the inguinal canals. A rudimentary penis was located dorsal to the penile urethra with no appreciable urethral process. A tiny external urethral orifice was discerned only after liquid was injected into the lumen of the cystic structures, confirming their identity as urethral dilatations. The dilatations were separated by a constricting band of fibrous tissue. No other significant findings were detected. This case illustrates a combination of congenital anomalies including bilateral cryptorchidism with scrotal absence, segmental urethral hypoplasia, and urethral dilatation, most likely associated with the intersex condition seen in polled breeds. The continued production and use of small ruminants as animal models demands the prompt recognition of congenital anomalies. This case also exemplifies the precautions required when breeding goats with polled ancestry.