Aprosencephaly with Otocephaly in a Lamb (Ovis aries)

Abstract

Aprosencephaly is a rare condition in veterinary and human medicine characterized by the complete absence of telencephalon and diencephalon. Some cases are accompanied by a facial dysmorphism designated as otocephaly. A stillborn lamb had splanchnocranial anomalies that were classified by computed tomography, magnetic resonance imaging, and pathologic examination as aprosencephaly and otocephaly. The brain included parts of the cerebellum and brainstem but no telencephalon, diencephalon, or mesencephalon. The cerebellum had a structurally normal cortex with expression of neuronal nuclear antigen in the inner and doublecortin in the outer granular cell layers, as well as an irregularly situated nucleus dentatus. Aprosencephaly with otocephaly has been described in mice with heterozygous mutations in the Otx2 gene; however, no causative polymorphisms were detected in the Otx2 gene region of this lamb.

A de novo variant in OTX2 in a lamb with otocephaly

“…The syndromic phenotype was characterized by microstomia, aglossia, palatoschisis, agnathia and synotia, and differed from previous similar case reports in sheep with synotia, otocephalus aprosopus or acephaly [7][8][9]. In a single stillborn lamb with splanchnocranial anomalies that were classified as aprosencephaly and otocephaly, an association with the OTX2 gene was ruled out [6]. Recently, morphological details of a single strophocephalic lamb with facial anomalies allocated to holoprosencephaly were presented but no molecular genetic examination was performed [14].…”

“…So far, all the OTX2related cases were heterozygous and mostly due to dominantly acting de novo variants, whereas the pathogenic variants described in the PRRX1 gene were either recessively or dominantly inherited [4]. Similar congenital anomalies including different syndromic forms of otocephaly occur also in domestic animals, for example in dogs (OMIA 001127-9615) [5], cattle (OMIA 001127-9913), and sheep (OMIA 000023-9940) [6][7][8][9]. In a single case of ovine agnathia karyotyping revealed a diseasecausing reciprocal translocation [10].…”

A Cyclopia Case with Otocephaly in a Pirlak Lamb

“…In recent years, it is revealed that OTX and PRRX gene mutations in humans cause otocephaly (FayePetersen et al 2006, Gekas et al 2010. However, no relationship between OTX2 gene and otocephaly was found in ewes (Brachthäuser et al 2012). In ruminants, there are some viral factors affecting the brain and nervous system of the fetus such as Akabane, Aino, Bluetongue, Border disease, Cache Valley, Schmallenberg virus during pregnancy.…”

“…Furthermore, some authors reported that these viruses could cause arthrogryposis, hydranencephaly, microcephaly and cerebellar hypoplasia defects (Givens and Marley 2008, Brachthäuser et al 2012, Pawaiya and Gupta 2013. Based on anamnesis at the same grazing region, there was no malformation case seen either in the herd that the case was observed or in the other closer herds.…”

“…In otocephaly cases of human-beings, one or multiple malformations can be observed together in mouth, tongue, eyes, nose and brain (Faye-Petersen et al 2006, Gekas et al 2010). However, it is rarely seen in animals (Pourlis 2006, Brachthäuser et al 2012. It is thought that the first and the second arch defects causes to otocephaly.…”