Uner Tan Syndrome: History, Clinical Evaluations, Genetics, and the\ud Dynamics of Human Quadrupedalism

Abstract: This review includes for the first time a dynamical systems analysis of human quadrupedalism in Uner Tan syndrome, which is characterized by habitual quadrupedalism, impaired intelligence, and rudimentary speech. The first family was discovered in a small village near Iskenderun, and families were later found in Adana and two other small villages near Gaziantep and Canakkale. In all the affected individuals dynamic balance was impaired during upright walking,and they habitually preferred walking on all four extremities. MRI scans showed inferior cerebellovermian hypoplasia with slightly simplified cerebral gyri in three of the families, but appeared normal in the fourth. PET scans showed a decreased glucose metabolic activity in the cerebellum, vermis and, to a lesser extent the cerebral cortex, except for one patient,\ud whose MRI scan also appeared to be normal. All four families had consanguineous marriages in their pedigrees,\ud suggesting autosomal recessive transmission. The syndrome was genetically heterogeneous. Since the initial discoveries\ud more cases have been found, and these exhibit facultative quadrupedal locomotion, and in one case, late childhood onset. It has been suggested that the human quadrupedalism may, at least, be a phenotypic example of reverse evolution. From the viewpoint of dynamic systems theory, it was concluded there may not be a single factor that predetermines human quadrupedalism in Uner Tan syndrome, but that it may involve self-organization, brain plasticity, and rewiring, from the many decentralized and local interactions among neuronal, genetic, and environmental subsystems

Development of bipedal and quadrupedal locomotion in humans from a dynamical systems perspective

The first phase in the development 0f locomotion, pr,öary variability would occur in normal fetuses and infants, and those with Uner Tan syndrome. The neural networks for quadrupedal locomotion have apparently been transmitted epigenetically through many species since about 400 MYA.\ud The second phase is the neuronal selection process. During infancy, the most effective motor pattern(s) and their associated neuronal group(s) are selected through experience.\ud The third phase, secondary or adaptive variability, starts to bloom at two to three years of age and matures in adolescence. This third phase may last much longer in some patients with Uner Tan syndrome, with a considerably delay in selection of the well-balanced quadrupedal locomotion, which may emerge very late in adolescence in these cases

THE PSYCHOMOTOR THEORY OF HUMAN MIND

This study presents a new theory to explain the neural origins of human mind. This is the psychomotor theory. The author briefly analyzed the historical development of the mind-brain theories. The close relations between psychological and motor systems were subjected to a rather detailed analysis, using psychiatric and neurological examples. The feedback circuits between mind, brain, and body were shown to occur within the mind-brain-body triad, in normal states, and psycho-neural diseases. It was stated that psychiatric signs and symptoms are coupled with motor disturbances; neurological diseases are coupled with psychological disturbances; changes in cortico-spinal motor-system activity may influence mind-brain-body triad, and vice versa. Accordingly, a psychomotor theory was created to explain the psychomotor coupling in health and disease, stating that, not themind-brain duality or unity, but themind-brain-body triad as a functional unit may be essential in health and disease, because mind does not end in the brain, but further controls movements, in a reciprocal manner; mental and motor events share the same neural substrate, cortical, and spinalmotoneurons;mental events emerging from the motoneuronal system expressed by the human language may be closely coupled with the unity of the mind-brain-body triad. So, the psychomotor theory rejects the mind-brain duality and instead advances the unity of the psychomotor system, which will have important consequences in understanding and improving the human mind, brain, and body in health and disease

Unertan Syndrome Quadrupedality,Primitive Language, and Severe Mental Retardation A New Theory on the Evolution of Human Mind

The recently discovered “UNERTAN SYNDROME” consists of quadrupedal gait, severe mental retardation, and primitive language. This syndrome can be considered as devolution of human being, throwing a light into the transition from quadrupedality to bipedality with co-evolution of human mind. The genetic nature of this syndrome supports the punctuated evolution during transition from quadrupedality to bipedality. In light of Tan’s psychomotor theory, accentuating the major role of the motor system in human mind, a new theory was suggested for the human evolution. Namely, the unique behavioral trait of man, the emergence of the habitual bipedality with Homo erectus (1.6 million and 250.000 years ago) may be coupled with a resistive mind, which forced man to stand up against the gravitational forces with consequent success in tool making and hunting, using free hands for survival. The second stage in the evolution of modern human beings may be coupled with the emergence of language (circa 40.000 years ago), playing a major role in the origins of human mind

A NEW SYNDROME WITH QUADRUPEDAL GAIT, PRIMITIVE SPEECH, AND SEVERE MENTAL RETARDATION AS A LIVE MODEL FOR HUMAN EVOLUTION

The author has discovered a new syndrome with quadrupedal gait, flexed head and body, primitive speech, severe mental retardation, and mild cerebellar signs with a disturbed conscious experience. This syndrome was exhibited by 5 of 19 children from a consanguineous family. The pedigree demonstrated a typical autosomal-recessive inheritance. The genetic nature of this syndrome suggests a backward stage in human evolution, which is most probably caused by a genetic mutation, rendering, in turn, the transition from quadrupedality to bipedality. This would then be consistent with theories of punctuated evolution. On the other hand, the extensor motor system causing a resistance of the body against the gravity may actually be subjected to evolutionary forces. This new syndrome may be used as a live model for human evolution

Two New Cases of Uner Tan Syndrome: One Man\ud with Transition from Quadrupedalism to Bipedalism;\ud One Man with Consistent Quadrupedalism

Background: Uner Tan syndrome, first described in\ud 2005, consists of three main symptoms: habitual\ud locomotion on all four extremities, impaired\ud intelligence, and dysarthric or no speech. This\ud extremely rare syndrome shows an autosomal\ud recessive inheritance due to consanguineous\ud marriages between parents. In general, there is a\ud cerebellovermial hypoplasia with a mild gyral\ud simplification in the cerebral cortex. Truncal ataxia is\ud the main neurological finding, causing difficulty in\ud standing and upright walking on two legs.\ud Methods: As soon as the new cases came to light, the\ud family was visited. After taking the basic information\ud about the family members, the traditional neurological\ud examinations were performed, MRI scans of the\ud patients and of a healthy family member were taken in\ud a hospital nearest to the residence (a small village\ud near Kars, Turkey). The patients were also filmed to\ud analyze their walking patterns.\ud Results: Two individuals (case 1, 44y; case 2, 43y)\ud among six siblings from a family with consanguineous\ud parents exhibited Uner Tan syndrome, with\ud quadrupedalism, impaired intelligence, and dysarthric\ud speech. Their pedigree suggested an autosomal\ud recessive inheritance. MRI scans showed inferior\ud cerebellovermial and pontobulbar hypoplasia.\ud Case 1 did not display hypotonia, while case 2 had\ud been hypotonic for two years after birth. Case 2’s\ud hypotonia progressively disappeared, and at three\ud years old he started to sit, and could walk on all fours\ud by the age of four. Case 1 was quadrupedal for 20\ud years, and then walked upright with the aid of a\ud walking stick. Tendon reflexes were normal in case 1\ud but hyperactive in the lower extremities of case 2;\ud Babinsky was absent in case 1 but bilaterally present\ud in case 2. There was no nystagmus, no strabismus,\ud and no pes pedus in either case. Cognition was\ud severely impaired in both.\ud Conclusion: The emergence of quadrupedalism\ud during development, with a transition into bipedalism\ud in case 1, and the emergence of the quadrupedalism\ud after a full hypotonia and no locomotion in case 2,\ud were considered as examples of the processes of\ud adaptive self-organization, from the viewpoint of\ud dynamic systems theory

Human quadrupedalism is not an epiphenomenon caused\ud by neurodevelopmental malformation and ataxia

Two cases with quadrupedal locomotion (QL) were presented. In both cases, cognitive and psychiatric functions were normal and, no neurological deficits were observed, except for a sequel paralysis of left leg in Case 2. It was suggested that human QL (1) should not be considered as an epiphenomenon caused by neurodevelopmental malformation and\ud ataxia, but (2) may be considered as a re-emergence of the ancestral diagonal QL, and (3) it may spontaneously emerge in humans with entirely normal brains, by taking advantage\ud of neural networks such as central pattern generators that have been preserved for about 400 million years

EVIDENCE FOR "UNER TAN SYNDROME" AS A HUMAN MODEL FOR REVERSE EVOLUTION

“Uner Tan Syndrome” was further studied in a second family. There was no cerebellar atrophy, except a mild vermial atrophy in MRI scans of the affected individuals. This is not, however, the pathogenesis of the “Uner Tan Syndrome”, since in the first and second families there were bipedal men exhibiting very similar MRI scans. The second family may also be considered a live model for reverse evolution in human beings. The present work provided evidence for a reverse evolution: (i) quadrupedality; (ii) primitive mental abilities including language; (iii) curved fingers during wrist-walking of the quadrupedal woman; (iv) arm to leg ratios being close to those of the human-like apes. The quadrupedal individuals were raised in separate places, so that they could not imitate each other, excluding the socio-cultural factors contributing to the habitual quadrupedal gait. The results are consistent with the single gene theory, suggesting a single gene controlling multiple behavioral traits, and the psychomotor theory, and a co-evolution of the human mind, an emergent property of the motor system expressed by human language

Üner Tan Syndrome: Review and Emergence of Human Quadrupedalism in Self-Organization,\ud Attractors and Evolutionary Perspectives\ud

The first man reported in the world literature exhibiting habitual quadrupedal locomotion was discovered by a British traveler and writer on the famous Baghdat road near Havsa/Samsun on the middle Black-Sea coast of Turkey (Childs, 1917). Interestingly, no single case with human quadrupedalism was reported in the scientific literature after Child's first description in 1917 until the first report on the Uner Tan syndrome (UTS: quadrupedalism, mental retardation, and impaired speech or no speech)in 2005 (Tan, 2005, 2006). Between 2005 and 2010, 10 families exhibiting the syndrome were discovered in Turkey with 33 cases: 14 women (42.4%) and 19 men (57.6%). Including a few cases from other countries, there were 25 men (64.1%)and 14 women (35.9%). The number of men significantly exceeded the number of women (p < .05). Genetics alone did not seem to be informative for the origins of many syndromes, including the Uner Tan syndrome. From the viewpoint of dynamical systems theory, there may not be a single factor including the neural and/or genetic codes that predetermines the emergence of the human quadrupedalism.Rather, it may involve a self-organization process, consisting of many decentralized and local interactions among neuronal, genetic, and environmental subsystems. The most remarkable characteristic of the UTS, the diagonal-sequence quadrupedalism is well developed in primates. The evolutionarily advantage of this gait is not known. However, there seems to be an evolutionarily advantage of this type of locomotion for primate evolution, with regard to the emergence of complex neural circuits with related highly complex structures. Namely, only primates with diagonal-sequence quadrupedal locomotion followed an evolution favoring larger brains, highly developed cognitive abilities with hand skills, and language, with erect posture and bipedal locomotion, creating the unity of human being. It was suggested that UTS may be considered a further example for Darwinian diseases, which may be associated with an evolutionary understanding of the disorders using evolutionary principles, such as the natural selection. On the other hand, the human quadrupedalism was proposed to be a phenotypic example of evolution of reverse, i.e., the reacquisition by derived populations of the same character states as those of ancestor populations. It was also suggested that the emergence of the human quadrupedalism may be related to self-organizing processes occurring in complex systems, which select or attract one preferred behavioral state or locomotor trait out of many possible attractor states. Concerning the locomotor patterns, the dynamical systems in brain and body of the developing child may prefer some kind of locomotion, according to interactions of the internal components and the environmental conditions, without a direct role of any causative factor(s), such as genetic or neural codes, consistent with the concept of self-organization, suggesting no single element may have a causal priority

UNERTAN SYNDROME: A CASE SERIES DEMONSTRATING HUMAN DEVOLUTION

A large family with six individuals exhibiting the Unertan syndrome (UTS)was identified residing in southern Turkey. All of the individuals had mental impairments and walked on all four extremities. The practice of intra-familial\ud marriages suggested that theUTS may be an autosomal recessive disorder, similar to previously described cases. The inferior portions of the cerebellum and vermis were\ud absent as evidenced by MRI and CT scans. The height and head circumference of those affected were within normal ranges. Barany’s test suggested normal vestibular\ud system function. The subjects could not name objects or their close relatives. The males (n = 4) could understand simple questions and commands, but answered questions with only one or two sounds. The females (n = 2) were superior to\ud the males with respect to language skills and walking, suggesting an association between walking and speaking abilities. One male exhibited three walking patterns\ud at the same time: quadripedal, tiptoe, and scissor walking. Another male used two walking styles: quadripedal and toe-walking. It is emphasized that there are important differences between the UTS and the disequilibrium syndrome. It is suggested that the inability to walk upright in those affected with the UTS may be\ud best explained by a disturbance in lateral-balance mechanisms,without being related to the cerebello-vestibular system.An interruption of locomotor development during the transition from quadripedality to bipedality may result in habitual walking on all four extremities and is normal in some children. Because quadripedal\ud gait is an ancestral trait, individuals with the UTS, exhibiting a manifestation of reverse evolution in humans, may be considered an experiment of nature, useful\ud in understanding the mechanisms underlying the transition from quadripedality to bipedality during human evolution. The proposed mutant gene or gene pool playing\ud a role in human quadrupedality may also be responsible for human bipedality at the same time. Herein there is no intent to insult or injure; rather, this report is an\ud endeavor to better understand human beings. Supplementary materials are available for this article. Go to the publisher’s online edition of International Journal of\ud Neuroscience for the following free supplemental resource(s): video clips