Alobar Holoprosencephaly in an Aborted American Quarter Horse Fetus.

Holoprosencephaly is a central nervous system malformation, characterized by incomplete or total lack of division of prosencephalon hemispheres, which is commonly accompanied by craniofacial malformations. A 9-month-gestation aborted American Quarter Horse fetus was submitted for postmortem examination. The fetus lacked haircoat and had severe facial malformations including marked shortening/absence of the maxillary, incisive and nasal bones, bilateral anophthalmia, and pre-maxillary agenesis. The prosencephalon was small and nearly spherical, represented by a single lobe, with no visible separation between cerebral hemispheres. The olfactory bulbs, piriform lobes, and the optic chiasm were absent. At cross sectioning of the prosencephalon, the inner structures of the brain were completely absent, and replaced by a monoventricle lined by the remaining compressed cortex, and the thalami were fused. Since mutations in the sonic hedgehog (SHH) gene have been associated with human holoprosencephaly, the three coding SHH exons were sequenced using liver DNA of the aborted foal. The obtained SHH sequence was similar to the Equus caballus SHH mRNA sequence deposited in Genbank (XM_023640069.1); therefore, no polymorphism in the coding region of this gene justifying the phenotype was observed. This is the first report of alobar holoprosencephaly in horses.

De novo ZIC2 frameshift variant associated with frontonasal dysplasia in a Limousin calf.

BACKGROUND: Bovine frontonasal dysplasias like arhinencephaly, synophthalmia, cyclopia and anophthalmia are sporadic congenital facial malformations. In this study, computed tomography, necropsy, histopathological examinations and whole genome sequencing on an Illumina NextSeq500 were performed to characterize a stillborn Limousin calf with frontonasal dysplasia. In order to identify private genetic and structural variants, we screened whole genome sequencing data of the affected calf and unaffected relatives including parents, a maternal and paternal halfsibling. RESULTS: The stillborn calf exhibited severe craniofacial malformations. Nose and maxilla were absent, mandibles were upwardly curved and a median cleft palate was evident. Eyes, optic nerve and orbital cavities were not developed and the rudimentary orbita showed hypotelorism. A defect centrally in the front skull covered with a membrane extended into the intracranial cavity. Aprosencephaly affected telencephalic and diencephalic structures and cerebellum. In addition, a shortened tail was seen. Filtering whole genome sequencing data revealed a private frameshift variant within the candidate gene ZIC2 in the affected calf. This variant was heterozygous mutant in this case and homozygous wild type in parents, half-siblings and controls. CONCLUSIONS: We found a novel ZIC2 frameshift mutation in an aprosencephalic Limousin calf. The origin of this variant is most likely due to a de novo mutation in the germline of one parent or during very early embryonic development. To the authors' best knowledge, this is the first identified mutation in cattle associated with bovine frontonasal dysplasia.

Aventriculi associated with holoprosencephaly in a dog.

CASE DESCRIPTION: A 10-month-old neutered male mixed breed dog was presented for assessment of poorly controlled seizures. CLINICAL FINDINGS: Magnetic resonance imaging of the brain disclosed complete absence of the lateral and third ventricles and mesencephalic aqueduct. Postmortem computed tomographic (CT) imaging and positive contrast cisterno-ventriculography confirmed the lack of a contiguous ventricular system. However, histopathology identified the presence of vestigial lateral and third ventricles with hypoplastic choroid plexus, atresia of the third ventricle, and fused thalami, consistent with a diagnosis of lobar holoprosencephaly (HPE). CLINICAL RELEVANCE: To our knowledge, this report is the first case of radiographically confirmed aventriculi associated with HPE, a rare congenital malformation previously reported in people, to be described in veterinary medicine.

Lobar holoprosencephaly with craniofacial defects in a Friesian calf: A case report.

BACKGROUND: Holoprosencephaly is a forebrain deformity that results from varying degrees of separation failure of cerebral hemispheres. The condition is classified based on the degree of non-separation of the hemispheres which, in turn, determines its severity. Holoprosencephaly is usually accompanied by craniofacial defects whose severity tends to reflect the extent of brain deformities. In humans, holoprosencephaly is one of the commonest congenital brain anomalies but in animals, reported cases are scarce. The condition has multifactorial aetiology that involves interactions between several genetic and environmental factors. CASE PRESENTATION: A 4-day-old female Friesian calf with a deformed face was reported to the Faculty of veterinary medicine and surgery, Egerton University. The calf and the dam were sired by the same bull. On clinical and radiographic examination, the calf had a short snout that curved dorsally with bilateral cleft lip, right-sided cleft jaw and a largely absent primary palate. Anatomopathological examination revealed brain deformities which included ventral fusion of frontal lobes of cerebral hemispheres, large merged lateral ventricles without septum pellucidum and fornix, hypoplastic corpus callosum, high degree of non-separation between diencephalic structures, poorly developed hippocampal formation and hypoplastic olfactory lobe, optic chiasma, and nerve. CONCLUSION: The case was confirmed as lobar holoprosencephaly based on characteristic anatomopathological findings. The aetiology of the defects in the present case could not be determined though they are thought to be either a result of recessive inheritance or exposure to teratogenic steroid alkaloids through materials fed to the dam during early pregnancy.

Cellular identities in an unusual presentation of cyclopia in a chick embryo.

Cyclopia is a congenital anomaly characterized by the presence of a single or partially divided eye in a single orbit at the body midline. This condition is usually associated with other severe facial malformations, such as the absence of the nose and, on rare occasions, the presence of a proboscis located above the ocular structures. The developmental origin of cyclopia in vertebrates is the failure of the embryonic prosencephalon to divide properly during the formation of the two bilateral eyes. Although the developmental origin of the cyclopia-associated proboscis is not clear, it has been suggested that this unique structure results from the disrupted morphogenesis of the olfactory placodes, the main organizers of the developing nose. In this study, we report a spontaneous congenital case of cyclopia with a proboscis-like appendage in a chick embryo. By means of both conventional histology and immunohistochemical methods, we have analyzed this anomaly in detail to suggest an alternative identity for the anatomical embryonic features of cyclopic vertebrate embryos displaying a proboscis. Our findings are discussed in the context of previously reported cases of cyclopia, and provide additional insight into this complex congenital malformation.

External and computed tomography analysis of a strophocephalic lamb.

CONTEXT: The Museum of Anatomy and Embryology Louis Deroubaix attached to the Laboratory of Anatomy, Biomecanics and Organogenesis, ULB, Brussels, possesses in its liquid collections a cephalic extremity of a lamb suffering from strophocephaly. The origins have not been determined. The trunk and the limbs are resected. MATERIAL AND METHODS: The piece has been studied and photographed. A volumic computed tomography acquisition has been performed with a Siemens Volume Zoom. For pedagogic and museological purposes, surface reconstructions and 3D printing have been obtained. RESULTS: An otocephaly is observed. Both ears are located in place of the oral cavity. The mandible is welded to the braincase. The eyeballs are close together (synophtalmia) which confirms the presence of a cyclotocephaly. They are surmounted by a rudimentary snout rather than a proboscis. The presence of this muzzle allows the anomaly to be classified as a strophocephaly, a malformation already described in sheeps. CT slices of the brain show a semi-lobar holoprosencephaly with incomplete division of the cerebral hemispheres and ventricules. DISCUSSION AND CONCLUSION: The CT examination allows the facial anomalies to be allocated to a holoprosencephaly. The singularity of this case, compared to the human cyclotocephalies, is the presence of a differentiated muzzle rather than a simple proboscis. The holoprosencephaly is uncomplete. Such anomalies have been associated with an entire absence of cerebral differentiation but with a complete absence of the muzzle. The tridimensional printing represents an interesting educational tool easily transportable in contrast to the original specimen.

Holoprosencephaly and Pure Red Cell Aplasia in a Feline Leukaemia Virus-Positive Kitten.

A 9-month-old, female, domestic longhair cat with severe anaemia tested positive for feline leukaemia virus (FeLV) and was humanely destroyed and submitted for necropsy examination. Gross findings included a non-divided rostral telencephalon, consistent with semilobar holoprosencephaly. Histological examination of the bone marrow revealed an almost complete absence of erythroid precursor cells, consistent with pure red cell aplasia, and mild to moderate myelofibrosis. This case demonstrates a very unusual central nervous system defect, as well as an atypical presentation of pure red cell aplasia, in a FeLV-positive kitten.

Semilobar Holoprosencephaly Associated with Multiple Malformations in a Foal.

A full-term male foal born in a farm holidays in Maremma (Tuscany, Italy) was euthanized shortly after birth due to the presence of several malformations. The rostral maxilla and the nasal septum were deviated to the right (wry nose), and a severe cervico-thoracic scoliosis and anus atresia were evident. Necropsy revealed ileum atresia and agenesis of the right kidney. The brain showed an incomplete separation of the hemispheres of the rostral third of the forebrain and the olfactory bulbs and tracts were absent (olfactory aplasia). A diagnosis of semilobar holoprosencephaly (HPE) was achieved. This is the first case of semilobar HPE associated with other organ anomalies in horses.

Multiple complex congenital malformations in a rabbit kit (Oryctolagus cuniculi).

Congenital malformations may occur during early embryogenesis in cases of genetic abnormalities or various environmental factors. Affected subjects most often have only one or 2 abnormalities; subjects rarely have several unrelated congenital defects. Here we describe a case of a stillborn New Zealand white rabbit with multiple complex congenital malformations, including synophthalmia, holoprosencephaly, gastroschisis, and a supernumerary hindlimb, among other anomalies. There was no historical exposure to teratogens or other known environmental causes. Although not confirmed, this case was most likely a rare spontaneous genetic event.

Congenital ocular and adnexal disorders in reptiles.

Ocular and adnexal congenital disorders are those that manifest at birth and could involve single or multiple tissues. Several abnormalities have been reported in literature affecting reptilian ocular and/or adnexal tissues. The objectives of this review are: (i) review those disorders previously reported in reptile literature; (ii) present new cases; (iii) provide a basic classification of them according to the moment of occurrence and (iv) indirectly, encourage the clinician dealing with these cases to go further in their diagnosis. The authors consider that categorizing ocular and adnexal congenital disorders could help the clinician to deal with them. The categorization of these disorders required an intense review of cases previously reported in literature and allows the authors suspect that some of them could not have been accurately diagnosed according to the definitions of the anomalies and/or not accurately described. The authors consider that ocular and adnexal congenital disorders could have been underestimated in reptiles and further studies could be helpful to promote the description of new disorders and to expand the knowledge about those previously reported. The review will first describe abnormalities reported during organogenesis (describing possible etiopathogenesis, cases reported, an approach to their diagnosis and recommended therapeutic options).Then a mention of the ocular disorders occurring after organogenesis is made. These disorders are divided when possible in those affecting all or most part of the globe and those affecting only specific tissues (surface ectoderm, neurocrest and mesenchyma and neuroectoderm).

Ocular anomalies and holoprosencephaly in a lamb.

The brain and eyes from a 1-day-old, male mixed-breed lamb with bilateral microphthalmia were examined. Bilateral ventral colobomata of choroid, sclera, retina and optic nerve were accompanied by agenesis of the optic nerve, and dilated lateral and third ventricular cavities that communicated with the subarachnoid space. Abundant neuroretinal tissue extending through the colobomatous defect to retro-orbital connective tissue, the meningeal surface and ventricular system were identified by histologic examination. Positive immunolabeling of these structures for recoverin (a photoreceptor marker) established the retinal origin of ectopic structures. The optic nerve was replaced by a short fibrous stalk containing glial nests. Sections of brainstem revealed extensive architectural disorganization. A developmental abnormality resulting from defective optic nerve and retina compartmentalization, accompanied by abnormalities of midline development consistent with the holoprosencephaly syndrome, was diagnosed. These lesions are consistent with signaling defects in the sonic hedgehog signaling pathway. Genetic and toxic causes of sonic hedgehog signaling defects are discussed.

Atypical cyclopia in a brown swiss cross calf: a case report.

In this report, an atypical form of cyclopia is described in a stillborn Brown Swiss cross male calf. The changes were confined to the head. The most significant malformation was the presence of a median orbita-like opening that did not contain an eyeball. Other defects included prosencephalic aplasia, brachygnathia superior and arrhinia. The possible cause of this congenital defect could not be ascertained.

Lobar holoprosencephaly in a Miniature Schnauzer with hypodipsic hypernatremia.

A 9-month-old male Miniature Schnauzer was examined because of a lifelong history of behavioral abnormalities, including hypodipsia. Diagnostic evaluation revealed marked hypernatremia and a single forebrain ventricle. The behavioral abnormalities did not resolve with correction of the hypernatremia, and the dog was euthanatized. At necropsy, midline forebrain structures were absent or reduced in size, and normally paired forebrain structures were incompletely separated. Findings were diagnostic for holoprosencephaly, a potentially genetic disorder and the likely cause of the hypodipsia. Similar evaluation of affected Miniature Schnauzer dogs may reveal whether holoprosencephaly routinely underlies the thirst deficiency that may be seen in dogs of this breed.

Holoprosencephaly in a long-tailed macaque (Macaca fascicularis): a case report.

A long-tailed macaque fetus with ethmocephaly, alobar holoprosencephaly, and arhinia is reported. This fetus was exposed to an antiprogestational agent, RU 486 (2.5 mg/kg intramuscular, once daily), during gestational days 15-18. Three hypotheses are proposed to explain these malformations: (1) they are a direct result of drug exposure, (2) they are a secondary effect of treatment and the result of decreased blood supply to the developing embryo due to an incomplete abortion, and (3) they represent a spontaneous occurrence.