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Genetics Uner Tan syndrome has been linked to intrafamilial marriage and reproduction, which suggests that it is an autosomal recessive disorder [2]. The main characteristic of this syndrome is habitual quadrupedalism, meaning they can stand up straight until they try to move, then they walk on their hands and knees. According to Tan, the syndrome may be placed in its own category under types of cerebellar ataxias [2]. This simply means it is a type of disorder that involves the cerebellum becoming inflamed, resulting in lack of control of voluntary movements [3]. Uner Tan syndrome falls into this category because it has similar symptoms to other cerebellar ataxia disorders such as Disequilibrium Syndrome (DES-H) and Cayman Syndrome. These symptoms include truncal ataxia, dysarthria, nystagmus, and hypoplasia of the cerebellum and vermis [2]. Human geneticist Tayfun Ozcelik discovered homozygosity in a region on chromosome 9p24 in Uner Tan syndrome individuals [4]. The very low density lipoprotein receptor gene (VLDLR) is located in this region, which is involved in the migration of neuroblasts within the brain. Ozcelik found mutations in the VLDRL gene in affected individuals, and suggested that these specific mutations may lead to VLDRL deficiency during the development of the brain. This may affect the proper formation of cerebrocerebellar structures critical for upright walking, resulting in quadrupedal locomotion [4]. Other genes may also be involved in habitual quadrupedalism. For example, in some affected families, chromosome 17p13 was involved, while in other families 17p13 and 9p24 had no effect. This suggests the syndrome is genetically heterogeneous [1]. The problem with identifying the specific mutation that leads to Uner Tan syndrome is the fact that different mutations in a single gene can lead to a wide range of phenotypes. In the VLDLR gene, similar mutations may be responsible for different types of cerebellar ataxias that affect proper locomotion in humans [2].

References 1. Onat, O. E., Gulsuner, S., Bilguvar, K., Basak, A. N., Topaloglu, H., Tan, M., Tan. U., Gunel, M., & Ozcelik, T. ( 2012, Aug 15). Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupdeal locomotion. European Journal of Human Genetics. 21, 281-285. https://www.nature.com/articles/ejhg2012170 2. Ozcelik, T., Akarsu, N., Uz, E., Caglayan, S., Gulsuner, S., Onat, O.E., Tan, M, & Tan, U. (2008, Mar 18). Mutations in the very low density lipoprotein receptor VLDLR cause cerebellar hypoplasia and quadrupedal locomotion in humans. Proc Natl Acad Sci USA. 105 (11), 4232–6. doi: 10.1073/pnas.0710010105 3. Schmahmann, J. D. (2004, Aug 1). Cerebellar Cognitive Affective Syndrome. The Journal of Neuropsychiatry and Clinical Neurosciences. 16 (3), 367-378. https://neuro.psychiatryonline.org/doi/abs/10.1176/jnp.16.3.367 4. Tan, U. (2006, Mar). A new syndrome with quadrupedal gait, primitive speech, and severe mental retardation as a live model for human evolution. Int. J. Neurosci. 116 (3), 361–9. doi: 10.1080/00207450500455330