Radiographic and computed tomographic evaluation and gait analysis of Brazilian minipigs with syndactyly.

OBJECTIVE To characterize a population of Brazilian minipigs with naturally occurring syndactyly by use of plain radiographs and CT images and to evaluate kinetic and temporospatial variables by use of a pressure-sensing walkway. ANIMALS 10 Brazilian minipigs from 6 to 8 months of age (group 1, 5 healthy pigs [body weight, 10.5 to 18.5 kg]; group 2, 5 pigs with syndactyly [body weight, 7.5 to 18.0 kg]). PROCEDURES Forelimbs and hind limbs of all pigs were assessed by use of radiography and CT. Gait was analyzed by use of a pressure-sensing walkway. RESULTS All limbs of all pigs of group 2 had syndactyly. Two forelimbs had complex-1 syndactyly, and 8 forelimbs had complex-2 syndactyly. Four hind limbs had simple syndactyly, 1 hind limb had complex-1 syndactyly, and 5 hind limbs had complex-2 syndactyly. Kinetic and temporospatial values and symmetry indices did not differ between groups. Plantar and palmar surfaces of healthy pigs had 2 areas of maximum pressure, whereas plantar and palmar surfaces of pigs with syndactyly had only 1 area of maximum pressure. CONCLUSIONS AND CLINICAL RELEVANCE In this population of pigs, the most common type of syndactyly was complex-2, and comparison with the healthy group revealed no alteration in kinetic and temporospatial variables. Therefore, results suggested that syndactyly in young minipigs did not cause locomotor disturbances.

Bilateral tibial agenesis and syndactyly in a cat.

CASE DESCRIPTION: A three-year-old cat was referred to the Veterinary Teaching Hospital, University of Naples, Italy. The cat had severe pelvic limb deformity, and abnormal development of all four paws. CLINICAL FINDINGS: Radiographs revealed bilateral tibial agenesis, syndactyly, and digital hypoplasia. TREATMENT AND OUTCOME: No treatment was instituted because of the severity of the injury, the adaptation of the cat to the abnormal condition, and the owner's refusal to permit any treatment. CLINICAL RELEVANCE: Congenital limb deformities are rarely reported in the cat and tibial agenesis is considered a very rare disease. This congenital anomaly is well documented and classified in man, and it has been associated with other abnormalities in more complex syndromes. This paper reports clinical and radiographic findings in a cat affected by bilateral complete tibial agenesis associated with other congenital anomalies.

Polymelia and Syndactyly in a Swainson's Hawk (Buteo swainsoni).

A hatch-year Swainson's Hawk (Buteo swainsoni) recovered from Modoc County, California, US, on 12 August 2012 had malformations of the rear limbs consisting of bilateral polymelia and syndactyly. We describe the malformations and evaluate potential causes. Postmortem examination revealed varus rotation of both femurs and abnormal appendages originating from the distal medial surface of the tibiotarsi with two nonfunctional digits on the right leg and one digit on the left leg. There was syndactyly between digits III and IV of both feet. Avian pox viral dermatitis was present on the skin of the ventral abdomen. A definitive cause of the skeletal malformations was not identified.

A rare case of simple syndactyly in a puppy.

A case of non-syndromic, complete syndactyly involving all four limbs is described in a three-month-old male crossbreed dog for the first time. Syndactyly is a rare condition in most animal species, in dogs it has been infrequently reported. Findings of clinical, radiographic and cytogenetic analyses are described and demonstrate probably for the first time that numerical and structural chromosome aberrations are not involved in the pathogenesis of this case of syndactyly.

Surgical treatment of simple syndactylism with secondary deep digital flexor tendon contracture in a Basset Hound.

A five-month-old, female Basset Hound was presented for lameness associated with a fused 3rd and 4th digital pad on the left hind limb (simple incomplete syndactyly), and secondary contracture of the deep digital flexure tendon of the 3rd and 4th digit. An onychectomy of the third phalanx of the third and fourth digits was performed. Following the operation, the dog gained good use of the affected limb for one month until intermittent non-weight bearing lameness developed. A second surgery was performed six months later, partially removing the second phalanx of digits three and four. Follow-up reports indicate that the dog is doing well and is without lameness. This is the first report of deep digital flexor tendon contracture and surgical treatment of this complication in canine simple syndactylism.

Syndactyly in a litter of cats.

In this case report, we describe the clinical and radiographic features of a litter of kittens affected with complex syndactyly. We also provide guidelines for the diagnosis, possible treatment and prevention of propagation of this condition. This is the first report of syndactyly in a litter of kittens and syndactyly affecting both the pectoral and pelvic limbs.

Congenital syndactyly in cattle: four novel mutations in the low density lipoprotein receptor-related protein 4 gene (LRP4).

BACKGROUND: Isolated syndactyly in cattle, also known as mulefoot, is inherited as an autosomal recessive trait with variable penetrance in different cattle breeds. Recently, two independent mutations in the bovine LRP4 gene have been reported as the primary cause of syndactyly in the Holstein and Angus cattle breeds. RESULTS: We confirmed the previously described LRP4 exon 33 two nucleotide substitution in most of the affected Holstein calves and revealed additional evidence for allelic heterogeneity by the identification of four new LRP4 non-synonymous point mutations co-segregating in Holstein, German Simmental and Simmental-Charolais families. CONCLUSION: We confirmed a significant role of LRP4 mutations in the pathogenesis of congenital syndactyly in cattle. The newly detected missense mutations in the LRP4 gene represent independent mutations affecting different conserved protein domains. However, the four newly described LRP4 mutations do still not explain all analyzed cases of syndactyly.

The bovine aristaless-like homeobox 4 (ALX4) as a candidate gene for syndactyly.

The ALX4 (aristaless-like homeobox 4) gene encodes a paired-type homeodomain transcriptional activator and plays a major role in anterior-posterior pattern formation during limb development. Here, the cloning, genomic structure and expression of the bovine ortholog of the ALX4 gene are reported. The bovine ALX4 gene consists of four exons and is located on BTA15q28-->q29 in a region syntenic to HSA11p11.2. The transcribed ALX4 mRNA encodes a 397-amino-acid protein showing a paired-type homeodomain and a C-terminal stretch of amino acids known as the OAR- or aristaless domain. The predicted protein shares 92.5% identity to human and mouse ALX4 proteins and all three species share almost complete identity in the conserved domains. ALX4 expression was detected by reverse transcriptase polymerase chain reaction in bovine fetal limb bones. The ALX4 gene was evaluated as a candidate gene for bovine syndactyly which has been mapped on the telomeric region of cattle chromosome 15. Sequencing of the four exons with flanking sequences of the bovine ALX4 gene from a panel of 14 affected animals belonging to German Holstein, German Fleckvieh and crossbreds, and 27 unaffected individuals from German Holstein revealed five silent SNPs within the coding region out of eleven SNPs in total. Four SNPs were polymorphic in the affected animals, but in comparison to the genotyped unaffected individuals the genotype distribution showed no evidence for an association to the phenotype. Therefore our data indicate that the ALX4 gene can probably be excluded as candidate gene for bovine syndactyly in the examined animals.

Defective splicing of Megf7/Lrp4, a regulator of distal limb development, in autosomal recessive mulefoot disease.

Mulefoot disease (MFD) is an autosomal recessive disorder of phenotypically variable expression that causes syndactyly in certain strains of cows. MFD maps to a narrow interval on bovine chromosome 15 that is syntenic to human chromosome 11p12-p11.2. This region contains MEGF7/LRP4 (approved gene symbol LRP4), a gene that encodes a member of the multifunctional low-density lipoprotein receptor gene family. Targeted and naturally occurring mutations in the murine Megf7/Lrp4 gene, a putative coreceptor in the Wnt signaling pathway, cause polysyndactyly in the rodent. Thus, Megf7/Lrp4 is a strong candidate for the MFD mutation. Using PCR analysis of tissue samples and sperm from confirmed homozygous MFD carriers, we have identified a functional single base pair mutation in the affected animals. We show that a G --> A transition at the first nucleotide in the splice donor site of intron 37 completely disables this splice site. The abnormal splicing that is caused by this mutation predicts the generation of a dysfunctional membrane-anchored receptor lacking the normal cytoplasmic domain. These findings confirm that autosomal recessive loss-of-function mutations in Megf7/Lrp4 result in phenotypically similar forms of syndactyly in different mammalian species and that such mutations are the cause of MFD in bovines.

Identification of a doublet missense substitution in the bovine LRP4 gene as a candidate causal mutation for syndactyly in Holstein cattle.

Syndactyly in Holstein cattle is an autosomal recessive abnormality characterized by the fusion of the functional digits. This disorder has been previously mapped to the telomeric part of bovine chromosome 15. Here, we describe the fine-mapping of syndactyly in Holstein cattle to a 3.5-Mb critical interval using a comparative mapping approach and an extended pedigree generated by embryo transfer. We report genetic evidence for the exclusion of two genes previously suggested as candidates (EXT2 and ALX4) and describe the identification of a doublet mutation in complete linkage disequilibrium with syndactyly in one gene of the critical interval: LRP4. Finally, based on recent discoveries concerning the mouse mutants dan and mdig and a mouse knockout for Lrp4, we present solid evidence that the subsequent substitution in LRP4 exon 33 is a strong candidate causal mutation for syndactyly in Holstein cattle.

Genetic analysis of syndactyly in German Holstein cattle.

Congenital syndactyly with a variable number of affected feet was observed in eight black and white German Holstein calves. Analysis of the pedigree data revealed that all affected individuals could be traced back to a single founder. The pedigree was consistent with monogenic autosomal recessive inheritance and variable expressivity. Bovine syndactyly or "mulefoot" has been previously shown to map on the telomeric end of bovine chromosome 15 and we performed PCR genotyping of microsatellite markers spanning 27 cM of this chromosomal region to test the new cases for genetic linkage with the phenotype. The haplotype segregation confirmed the suggested inheritance pattern of the mulefoot mutation in this family and markers RM004, BM848 and BMS820 showed significant linkage to the phenotype. The results confirmed the chromosomal location of the mulefoot gene in this pedigree. Furthermore the study demonstrated that although marker testing has been available for nearly a decade the use of mulefoot carriers in cattle breeding remains uncontrolled. The presented family provides a resource for positional cloning of the causative mutation.

[Case report: Syndactyly in German Holstein calves]. / Syndaktylie bei Deutschen Holstein-Kälbern.

In 8 black and white German Holstein calves syndactyly was observed. The affected calves were born in different farms between 1995 und 2002. The number of feet affected varied from one, several to all four. All syndactylous calves could be traced back to a common ancestor, which was already identified as a carrier bull for the mulefoot gene. The pedigree was consistent with a monogenic autosomal recessive inheritance and variable expressivity.

Hereditary syndactyly in Angus cattle.

Twenty-five syndactylous Angus cattle, characterized pathologically, were reported from 16 herds in 10 states from 1979 to 1994. Twenty-one (84%) had all 4 legs syndactylous, 3 (12%) had 3 legs syndactylous, and 1 (4%) had 2 legs syndactylous. All syndactylous cattle walked with considerable difficulty. Hooves of aged animals became curled and bent laterally or medially. Affected hooves had the appearance of a truncated cone, the base of which was located at the coronary band. Most hooves were fused completely with no indication of dual anlage. An occasional hoof had a distal notch, and other hooves had a dorsally located groove indicating dual embryonic origin. Lateral dewclaws were enlarged in most cases. Radiographs and dissections of limbs of 19 animals revealed a consistent pattern of fusion in most affected calves. Lesions included 1 or more of the following: disappearance of the large metacarpal and metatarsal intertrochlear notches, horizontal fusion of 1 or more carpals and tarsals, fusion of proximal sesamoids, 1 distal sesamoid, and fusion of paired phalanges. Evidence of a genetic cause consisted of 11 syndactylous calves among 70 offspring of 4 3/4 sib families, 8 preterm syndactylous fetuses among 148 preterm fetuses and 13 calves in progenies of 19 animals tested for possible heterozygosity, and 5 syndactylous calves from matings of an Angus syndactylous bull with 1 Angus and 4 Holstein syndactylous cows. Data were consistent with recessive inheritance at a single locus. Angus cattle with sydactytly had a larger number of affected limbs than did syndactylous Holsteins and their Angus crosses, suggesting existence of 2 recessive alleles. The allele of Holsteins (syH) appeared to influence phenotypic expression in a dominant pattern over the Angus allele (syA). Both syA and syH alleles acted as recessives to the normal SY allele. Phenotypic effects on limb development were most dramatic in calves with the syA/syA genotype.

Identity-by-descent mapping of recessive traits in livestock: application to map the bovine syndactyly locus to chromosome 15.

Twelve animals affected with syndactyly or mulefoot were sampled in the Dutch black-and-white cattle population. Analysis of the pedigree data reveal that all of these individuals traced back to a single acknowledged carrier founder individual. Between seven and nine generations separated the founder from its 12 affected descendents. The 12 affected offspring were genotyped for a battery of 213 microsatellites spanning the 29 bovine autosomes. The resulting genotypes were analyzed using a maximum likelihood approach searching for shared homozygous haplotypes among affected individuals. Three candidate regions for the syndactyly locus emerged from this initial screening. syndactyly was shown to map to one of these candidate regions on chromosome 15 by genotyping 29 additional individuals linking founder and affected offspring and performing a conventional linkage analysis with the LINKAGE programs. This study illustrates the potential of identity-by-descent mapping in livestock populations.

Surgical management of syndactyly in a dog.

This report describes the treatment of simple syndactyly in a Golden Retriever. The left forepaw lacked cutaneous separation between the digits and had confluent metacarpal and digital pads. After vigorous exercise, the dog had intermittent non-weight-bearing lameness involving the affected forepaw. The lameness may have resulted from stretching of the thin skin on the dorsum of the paw as the digits attempted to spread during weight bearing. Surgical separation of digits 3 and 4 was performed by creating an interdigital web space with dorsal and palmar skin flaps and by covering the exposed axial surfaces with full-thickness skin grafts. At 11 weeks after surgery, the lameness had improved and the dog's level of activity had increased.

Syndactylism and brachygnathia in a white-tailed deer.

A white-tailed deer (Odocoileus virginianus) fawn was presented to the Southeastern Cooperative Wildlife Disease Study for examination of brachygnathia and syndactylous front feet. The hoof keratin of digits 3 and 4 was completely fused and typical sole integument covered the palmar surface between the primary digits. Based on a radiographic examination, there was fusion of the epiphyses of the first phalanges of digits 3 and 4 in both feet. In the right foot the proximal metaphyses of the first phalanges of digits 3 and 4 were fused.

Growth of the early bovine fetus.

Testing for bovine hereditary syndactyly used artificial insemination, superovulation, and embryo transfer. Thirty-two suspect bulls and 9 suspect cows were mated with 10 syndactyly cows and two syndactylous bulls, respectively. 209 embryos were recovered and one, two, or three embryos was/were transfered into each recipient cow and 56 to 77 days after transfer, 174 fetuses were recovered. There was a significant relationship between amniotic fluid weights from the left uterine horn, fetal weights from right and left uterine horns, and fetal sex, side of corpus luteum, and number of embryo implants. Fetal membrane weights, amniotic fluid weights, fetal weights, and crown-rump lengths increased significantly with fetal age, but recipient cow weight had no significant effect. Survival data from single, double, and triple embryo implants indicated that it was most profitable under these test conditions to implant two embryos per recipient cow, one in each uterine horn.

Hereditary bovine syndactyly: diagnosis in bovine fetuses.

Diagnostic guidelines were established for progeny testing of hereditary bovine syndactyly. Through the use of superovulation and embryo transfer, 139 fetuses were recovered at 50 to 77 days gestation. Normal (+/+, +/sy) and syndactylous (sy/sy) anatomy of Holstein fetuses was defined, and the accuracy of macroscopic versus microscopic limb diagnosis was assessed. Chondrification and ossification differences between normal (+/+, +/sy) and syndactylous (sy/sy) fetuses were only age-related. Normal (+/+, +/sy) fetal limbs differed from normal (+/+, +/sy) adult bovine limbs in two ways. Fetal metacarpal and metatarsal III and IV bones were not fused, and fetal metacarpal and metatarsal II and V bones often extended up to three-fourths the length of metacarpal and metatarsal III and IV bones. In syndactylous (sy/sy) fetuses, synostosis asymmetries occurred within and between fetal limbs, and between fetuses, representing variable gene expressivity. Synostosis pattern within limbs did not correspond with those of the adult bovine; the second phalangeal pair was synostotic most frequently in the fetus, followed by the first, and then the third pair. Synostosis patterns between fetal limbs agreed with those of the adult; there was a right-left and front-rear limb gradient. Partial synostoses occurred sporadically in all three paired phalanges. Those of the first and third pair always involved the tip closest to the second phalangeal pair. A unique example of variable gene expressivity occurred in one syndactylous fetus. Both front limbs were syndactylous, while both rear limbs were normal grossly. Microscopically the right rear limb was normal while the left rear limb consisted of closely apposed phalangeal blastemata without coalescence.(ABSTRACT TRUNCATED AT 250 WORDS)