Iniencephaly and other neural tube defects in a litter of ferrets (Mustela putorius furo).

Iniencephaly is a rare form of neural tube defect (NTD) that has been documented in human beings and rats,” but not in the European (domestic) ferret (Mustela putoriusfuro). The term iniencephaly, derived from the Greek word “inion,” meaning “the nape of the neck,” is applied to a syndrome characterized by the following features: 1) deficiency of the occiput, 2) rachischisis (congenital fissure of the spinal column) of variable degree, and 3) cervical retrofle~ion.~ In this report, we describe a litter of ferrets with multisystemic congenital malformations including iniencephaly. A litter of four ferret kits was presented to a veterinary practitioner following a term delivery. Three of the four were stillborn; the fourth died within minutes of delivery. The dam was an albino ferret, approximately 2.5 years old, and had given birth to two previous litters; these kits had no abnormalities. The sire of both litters was a 3-year-old “blackeyed white” ferret, a color-diluted strain with whitish-grey fur and dark eyes. This litter was the second litter born at this breeding operation with similar gross malformations; although the dams were different, the same sire was responsible for both litters. The first litter did not survive and were not available for examination. All fetuses were grossly abnormal. There was marked variation in nose-to-tail length that corresponded to the degree of dorsal cervical retroflexion in two fetuses and apparent intrauterinegrowth retardation in a third (Fig. 1). Two fetuses were iniencephalic with anencephaly (absence of cranial vault and cerebral hemispheres) (one shown in Fig. 2); a third had anencephaly and an omphalocele (Fig. 1, far right). Radiographic examination demonstrated marked cervical vertebral malformation with dorsal retroflexion in the two fetuses. Three fetuses had varying degrees of palatoschisis; two of the fetuses had unilateral or bilateral cheiloschisis. The single fetus without a skull defect exhibited hydrocephalus. Renal abnormalities were observed in several of the kits. One kit (No. 1) had unilateral renal agenesis, while the contralateral kidney was grossly cystic due to extreme hydronephrosis. One iniencephalic kit (No. 2) had bilateral hydronephrosis. Additional gross defects in the two iniencephalic fetuses (Nos. 2 and 3) included low-set eyes, low-set or absent ears, and protruding tongues. Histologic examination of the three anencephalic fetuses (Nos. 2-4) revealed an absence of cerebral tissue, with numerous prominent congested meningeal vessels (cerebrovasculosa). Fusion of multiple cervical and lumbar vertebral bodies was observed in one of the iniencephalic fetuses (No. 2) that had been sectioned longitudinally in toto (Fig. 3). Iniencephaly has rarely been reported in animal species and only under experimental conditions.” This paper represents the first report of spontaneous iniencephaly in domestic animals. There is no information on the genetic causes of this disorder in animals in the current literature.13 A significant correlation between number of previous litters and congenital malformations has been reported in ferrets, with cranioschisis occurring most often in kits delivered by female ferrets with two previous litters, as seen in this case.6 Iniencephaly has been experimentally induced in rats with the administration of the antineoplastic agents streptonigrin14 and vinblastine,’ as well as with triparanol, a cholesterol reducing agent.” Various combinations of rachischisis, anencephaly, and cleft palate have been observed in numerous animal species following administration of Vitamin A (retinoic acid).]” I Z