SMALL ROUNDED EARS MUTATION
Cats generally have prick (upright ears) which are triangular in shape. The size, set and exact shape varies from the small ears of Persian cats to the "bat-like" flared ears of some Siamese cats. Some breeds require the base to be more widely flared than others. Some breeds have ears placed close together high on the head, others have wide-set ears with a broad expanse of forehead between. The tips may be rounded, pointed, tufted or fringed depending on the breed.
Characterization of an Inherited Neurologic Syndrome in Toyger Cats with Forebrain Commissural Malformations, Ventriculomegaly and Interhemispheric Cysts, MK Keating, BK, Sturges, S Siso, ER Wisner, EK Creighton, LA Lyons, in J Vet Intern Med. 2016;30(2):617–626.
A small-eared male Oriental cat was imported from Italy to the USA to found a line of cats with small, rounded ears to use in developing the Toyger breed. The small, rounded ears appeared desirable to improve the tiger-like appearance of the breed. The male was mated to at least 4 mixed breed, unrelated female domestic cats, producing only normal-eared offspring with each. The F1 female offspring were then backcrossed to the short-eared male, producing some offspring with normal ears and some with short ears. Kittens from brother-sister matings produced similar results. Pedigree analysis showed the mutation to be an autosomal recessive i.e. not sex-linked. Short-eared females showed normal sexual behaviour, but never became pregnant when mated to short-eared males, carrier males or completely unrelated males. The foundation male was (obviously) fertile as were carrier males and females.
The short-eared kittens were “clumsy” and MRI scans found them to have marked ventricular dilatation and associated anomalies. 20 related Oriental-derived crossbred Toyger cats weres from the breeding programme were donated to UC Davis for study. Seven were clinically healthy carriers and 13 were cats showing neurological signs, short ear phenotype and complex brain anomalies (“affected cats”). MRI scans were performed on all of the cats. Following diagnostic studies, the cats were destroyed and their brain anatomy was studied. The affected cats had structural brain abnormalities such as ventriculomegaly, cysts and multiple midline and callosal malformations. The affected cats had varying degrees of dilated ventricles (fluid filled regions of the brain) and thinning of the cerebral cortex. The affected cats did not have the normal pattern of ridges and furrows on the brain surface – these were much shallower and had an abnormal pattern. The degree of shallowness corresponded to how severely the cat was affected. These congenital brain defects were found to underlie the neurologic signs observed in those cats selectively bred for the short ear phenotype.
There was an update to this study about small ears: A Deletion in GDF7 is Associated with a Heritable Forebrain Commissural Malformation Concurrent with Ventriculomegaly and Interhemispheric Cysts in Cats
Yoshihiko Yu, Erica K. Creighton, Reuben M. Buckley, Leslie A. Lyons and 99 Lives Consortium
Genes 2020, 11, 672
An inherited neurologic syndrome was documented in a family of cats involving forebrain commissural malformation, concurrent with ventriculomegaly and interhemispheric cysts. Commissural fibres connect the two hemispheres of the brain. Ventriculomegaly means the brain has enlarged fluid filled cavities. Interhemispheric cysts are fluid filled bodies between the 2 hemispheres of the brain and are associated with defective development of the bundle of nerve fibres that connect the two hemispheres and allow the left and right sides of the brain communicate with each other(corpus callosum).
It was inherited as an autosomal recessive syndrome. Forty-three cats were genotyped. A homozygous mutation was found in Growth Differentiation Factor 7 (GDF7) in affected cats. This was not found in 192 unaffected cats in the 99 Lives dataset. GDF7 is important in the development of neurons in the mammalian brain. A genetic allows cat breeders to identify carriers so they are not used in breeding.
During the development of the Toyger cat, in which small rounded ears are desirable, a mixed breed cat from Italy, with Oriental ancestry, with small rounded ears was used as a foundation sire. Outcross and backcross breeding found the small ear trait to be inherited as an autosomal recessive. MRI scans of a rounded-ear kitten following an accidental head injury due to a fall, showed there was congenital hydrocephalus. MRIs of the breeding stock suggested cats with small round-ear phenotype and domed heads had congenital brain malformations.
(Keating, M.K.; Sturges, B.K.; Siso, S.;Wisner, E.R.; Creighton, E.K.; Lyons, L.A. Characterization of an Inherited Neurologic Syndrome in Toyger Cats with Forebrain Commissural Malformations, Ventriculomegaly and Interhemispheric Cysts. J. Vet. Intern. Med. 2016, 30, 617–626.)
The cats with small rounded ears were “clumsy” and mildly unco-ordinated when walking. They had normal limb reflexes and normal cranial nerves, but their brains had abnormalities as described above. The findings resembled a mild form of holoprosencephaly (HPE) in humans. HPE means the brain doesn’t properly separate into 2 hemispheres. Most affected cats also had hydrocephaly (excessive fluid in the skull). There were no chromosomal abnormalities. It is a recessive trait and is not sex-linked.
The owner of the cats halted the breeding programme and neutered the cats. Some cats were presented to the researchers for pathologyl and genetic studies. Cats with normal sized and shaped ears had no clinical signs. The cats with small rounded ears showed characteristic clumsiness.
This paper noted that cat skull and brain malformations most often occur “out of the blue.” However, cats with a high degree of brachycephaly (short muzzle, flat face) are associated with malformed skull-caps, facial bones, abnormal teeth, compressed/absent tear ducts and/or respiratory abnormalities. An inherited craniofacial malformation with meningoencephalocele (a sac of fluid, brain tissue and brain membranes extending through a defect in the skull) found in Burmese cats was caused by a mutation in ALX Homeobox 1 (ALX1).
(Schmidt, M.J.; Kampschulte, M.; Enderlein, S.; Gorgas, D.; Lang, J.; Ludewig, E.; Fischer, A.; Meyer-Lindenberg, A.; Schaubmar, A.R.; Failing, K.; et al. The Relationship between Brachycephalic Head Features in Modern Persian Cats and Dysmorphologies of the Skull and Internal Hydrocephalus. J. Vet. Intern. Med. 2017, 31, 1487–1501. [CrossRef]
Schlueter, C.; Budras, K.D.; Ludewig, E.; Mayrhofer, E.; Koenig, H.E.; Walter, A.; Oechtering, G.U. Brachycephalic feline noses: CT and anatomical study of the relationship between head conformation and the nasolacrimal drainage system. J. Feline Med. Surg. 2009, 11, 891–900.
Farnworth, M.J.; Chen, R.; Packer, R.M.; Caney, S.M.; Gunn-Moore, D.A. Flat feline faces: Is brachycephaly associated with respiratory abnormalities in the domestic cat (Felis catus)? PLoS ONE 2016, 11, e0161777.
Mestrinho, L.A.; Louro, J.M.; Gordo, I.S.; Niza, M.; Requicha, J.F.; Force, J.G.; Gawor, J.P. Oral and dental anomalies in purebred, brachycephalic Persian and exotic cats. J. Am. Vet. Med. Assoc. 2018, 253, 66–72.
Sponenberg, D.P.; Graf-Webster, E. Hereditary meningoencephalocele in Burmese cats. J. Hered. 1986, 77, 60.
Lyons, L.A.; Erdman, C.A.; Grahn, R.A.; Hamilton, M.J.; Carter, M.J.; Helps, C.R.; Alhaddad, H.; Gandolfi, B. Aristaless-Like Homeobox protein 1 (ALX1) variant associated with craniofacial structure and frontonasal dysplasia in Burmese cats. Dev. Biol. 2016, 409, 451–458.)