Book Ch Latest Findings Tan 2012

0 votes
Book Ch Latest Findings Tan 2012
Author: Uner Tan
Publisher: Cukurova University
44 pages
One time payment: €0.00
Required subscription: Free
Type of publication: Article
ISBN/ISSN: 978-953-307-865-6
Follow this publisher

Share this publication:


Uner Tan syndrome (UTS), discovered in 2005 in Southern Turkey, mainly consists of


habitual quadrupedal locomotion, mental retardation, and dysarthric or no speech, with or


without cerebello-vermial hypoplasia and mildly simplified cortical gyri. A man walking on


all four extremities, probably exhibiting the symptoms of the UTS, was first discovered and


reported in 1917, nearly a hundred years ago, by a British traveler on the Middle Black Sea


coast, near Samsun, on the famous Baghdad road, during the time of the Ottoman Empire.


Between 2005 and 2010, 10 families with 33 cases—13 women (42.4%) and 19 men (57.6%)—


were discovered in Turkey (see Table 1). In addition, there were two male children (4 and 12


years old) resident in Adana and Istanbul, who were normal in cognitive abilities, with no


neurological signs and symptoms, and normal brain MRIs, but with facultative quadrupedal


locomotion. Including the cases from Brazil, Iraq, Mexico, and Chile, there were 25 men


(64.1%) and 14 women (35.9%) around the world. Statistics showed that the number of men


significantly exceeded the number of women (p<.05), suggesting a male preponderance in


UTS. Genealogical analysis suggested autosomal recessive transmission linked to


chromosome 17p13.1.13.3 with a missense mutation in the WDR81 gene in the affected


members of the first described Iskenderun family. Homozygocity was found in two families


resident in remote villages of Southern and Northern Turkey, and was mapped to a region


on chromosome 9p24 that included the very low density lipoprotein receptor gene, VLDLR.


These results suggested that UTS may be a genetically heterogeneous syndrome.


Interestingly, the mother of the affected siblings in the Iskenderun family had Type-I


diabetes, which may be associated with congenital malformations such as caudal regression


in mice, suggesting that the maternal diabetes in some cases with UTS could be associated


with neuronal damage, resulting in impaired balance.


UTS can be considered within the framework of the non-progressive autosomal recessive


cerebellar ataxias, which are associated with various genetic mutations. Among these


conditions, such as disequilibrium syndrome (DES), Cayman ataxia, and Joubert syndrome,


there are overlapping symptoms, like truncal ataxia, psychomotor delay, and dysarthric


speech. All of these syndromes show genetic heterogeneity, which is characteristic for many


diseases. Thus, genetics alone do not seem to be informative for the origins of many


syndromes, including UTS. From the viewpoint of dynamical systems theory, there may not


be a single factor including a genetic code that predetermines the emergence of human


quadrupedalism, seen, for instance, in UTS. Rather, it may involve a self-organization



Üner Tan Syndrome: Review and Emergence of



Human Quadrupedalism in Self-Organization, Attractors and Evolutionary Perspectives 33




process, consisting of many decentralized and local interactions among neuronal, genetic,


and environmental subsystems.


UTS was divided into two subgroups: Type-I and Type-II, the former exhibiting no


hypotonia, and the latter being associated with early hypotonia. The comparison with other


closely related syndromes, such as DES, Cayman ataxia, and Joubert syndrome, indicated


that UTS may be distinguished from these syndromes by habitual locomotion on all four


extremities, normal stature, and normal muscle tone in Type-I cases, but early hypotonia in


Type-II cases. For these reasons, UTS may be considered a distinct entity among the


cerebellar ataxias.


The most remarkable characteristic of UTS is diagonal-sequence quadrupedal locomotion,


similar to the non-human primates and contrary to non-primate species. The evolutionary


advantage of diagonal-sequence quadrupedal locomotion is not known. However,


interestingly, there seems to be an evolutionary 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, highly developed hand skills, and language, with erect posture and bipedal


locomotion, creating the unity of human beings. The non-primate mammals using lateralsequence


quadrupedal locomotion did not show a similar phylogenetic progress compared


to those with diagonal-sequence quadrupedal locomotion, which, in essence, was the


phylogenetically oldest type of locomotion since it was a characteristic of the first tetrapods


during the Devonian period. This suggests that the ancestral neural networks responsible


for the diagonal-sequence quadrupedal locomotion were reserved for at least nearly 400


million years since the Devonian tetrapod-like fishes.


The human quadrupedal locomotion seen in UTS showed some similarities with nonhuman


primates. For instance, the human quadrupeds supported their body weight more


on the feet than on the hands during quadrupedal locomotion, in a similar way to the


weight distribution during location in most non-human primates. In contrast, non-primate


quadrupedal mammals usually support their body weight more on the forelimbs than their


hind limbs. The body weight support patterns in non-human and human primates suggests


that the reduced body weight on hands than feet would be beneficial for the development of


fine hand skills in primates. The complete freeing of hands in human beings during upright


walking would be entirely associated with highly developed hand skills compared to the


non-human primates walking on all four extremities.


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 natural selection. In this context, UTS may also be


considered a disease with phylogenetic regression. In some UTS cases, the supraorbital tori


were remarkably prominent, and were more or less similar to those in non-human primates.


This was taken to be an ancestral feature, in addition to the diagonal-sequence quadrupedal


locomotion, and the body weight being supported predominantly by the hind legs.


Human quadrupedalism was proposed to be a phenotypic example of evolution in reverse,


i.e., the reacquisition by derived populations of the same character states as those of ancestor



34 Latest Findings in Intellectual and Developmental Disabilities Research




populations. On the other hand, UTS may be considered within the framework of


phylogenetic diseases (phylogenetic regression), which may be related to the phenotypic


backward evolutionary atavism (the reappearance of a lost character (either morphological


or behavioral) that was typical of remote ancestors). The habitual diagonal-sequence


quadrupedal locomotion, standing with bent knees and bent trunk (flexor posture contrary


to the extensor posture in modern human beings), prominent supraorbital tori, fist walking


with bent fingers, and non-opposable thumb, may be related to ancestral characteristics in


the UTS cases. The diagonal-sequence quadrupedal locomotion (habitual or facultative) was


also the preferred gait of some individuals with entirely normal brains, probably as a result


of the neural networks preserved during nearly 400 million years of evolution.


The emergence of human quadrupedalism was related to the self-organizing processes


occurring in complex systems, which selects or attracts one preferred behavioral state or


locomotor trait out of many possible attractor states. Since this is a spontaneous and


unpredictable event, behavioral variability being a common precursor, the dynamic


systems provide enormous flexibilities. According to the interactions of the internal


components with their sensitivities to external conditions, the complex dynamical systems


prefer a behavioral mode or modes. Concerning the locomotor patterns, the dynamical


systems (brain and body) of the developing child may prefer or create some kind of


locomotion, according to interactions of the internal components and environmental


conditions, without a direct role of any causative factor(s), such as genetic or neural codes.


This self-organization occurs through the interactions of its components, endogenously


(within the brain), and/or exogenously through some environmental influence, but


without any external force.


The emergence of human locomotion is a developmental event in which the selforganization


processes play the major role, suggesting no innate or previously prescribed


codes are essential for the emergence of walking during locomotor development. The


developing skeleto-motor system of the individuals with impaired balance may selforganize,


which is itself triggered by the exogenous environmental constraints, and they will


then find the most suitable and most comfortable, and hence preferred, mode of locomotion,


spontaneously generating novel and organized forms and attractor states. In UTS, these


spontaneous, unpredictable strange attractors may include diagonal-sequence quadrupedal


locomotion, as also seen in the non-human primates, or an entirely unpredictable novel


quadrupedal locomotion may emerge, such as the inverse (face-up) quadrupedal


locomotion. More examples of the unpredictable, self-organized, and emergent strange


attractors were presented in this article. The contribution of the single factors such as the


genetic and/or neural codes (central pattern generators) to the emergence of the locomotor


patterns during locomotor development were rejected, considering the current scientific


research in these fields, consistent with the concept of self-organization, suggesting no


single element has causal priority.



About the publisher:










Honorary Member of the Turkish Academy of Sciences


Professional Member of the American Academy of Neuropsychology


Liaison Member of the American Psychological Association


Member of the World Innovation Foundation


Senior Researcher in Cukurova University








Place of birth: Unye, Ordu, Turkey


Date of birth : 1 May 1937








1945-1950: Primary School, Vezirkopru, Samsun, Turkey


1950-1954: Middle School and Lyceum, Osmancik and Corum, Turkey


1954-1956: Lyceum, Izmir, Turkey


1956-1960: Egean University, Medical School, Izmir, Turkey


1960-1966: Goettingen University, Medical School, Germany


1960-1966: Ph.D. Max-Planck Institute for Medical Research, Goettingen, Germany








1966-1967:Ass. Prof., Max-Planck Institute for Medical Reserach, Goettingen, Germany


1967-1969: Ass. Prof. Institute of Physiology, Goettingen University, Germany


1969-1973: Lecturer, Institute of Physiology, Hacettepe University, Ankara, Turkey


1973-1977: Assoc. Professor for Physiology, Medical Schools of Hacettepe (Ankara) and


     Ataturk (Erzurum) Universities, Turkey


1977-1999: Professor of Physiology, Ataturk University, Medical School, Erzurum,Turkey


1973-1999: Head of the Department of Physiology, Ataturk University, Erzurum, Turkey


1999-2002: Head of the Department of Physiology, Medical School, BlackSea Technical


     University, Trabzon, Turkey


2002-2004: Head of the Department of Neurophysiology Unit, Adana, Turkey








2002-2009:  Editor, International Journal of Neuroscience, USA


2002-2008: Editorial board, Perceptual and Motor Skills, USA


2002-present: Editor for Neurophysiology section in the Journal of Neuroquantology, Turkey


2008-present: Editorial Board in the Journal of Neuroquantology, Izmir, Turkey


2011: Editorial Board in “International Journal of Basic and Clinical Research” 


1980-present: Reviewer for the various international and national scientific periodicals










1973: Science Award for young scientists, Turkish Scientific and Technical Council


1986: Science Award, Turkish Scientific and Technical Council, Ankara, Turkey


1975: Eczacibasi Medical Award, Istanbul, Turkey, Istanbul, Turkey


1980: Dorothea Morton First Prize for Neurological Sciences, Istanbul, Turkey


1988: Sedat Simavi Medical Award, Istanbul, Turkey


1985: Ph. D., Honoris Causa in education, USA  


1986: Einstein Medals for science and peace, USA


1987: Medal of Honour, USA


1991: Nobel Medals for Science and Peace, Albert Einstein Foundation, USA


1992: Golden Academy Award for Lifelong Achievement, USA


1998: Gold Record for Brain Research, American Biographical Institute, USA








Turkish Academy of Sciences


American National Academy of Neuropsychology


New York Academy of Sciences


International Brain Research Organization


European Neuroscience Association


Society for Psychophysiological Research


National Societies for EEG, EMG, and Neurology


American Psychological Association


World Innovation Foundation








Physiology and pharmacology of the spinal and cerebral motor systems




Mechanisms of the effects of the antidepressant drugs


Microelectrode studies of the pyramidal neurons in cats


Asymmetric brain in mice, rats, cats, and humans


Primitive reflexes in human neonates


Sex differences in cerebral lateralization and cognition


Hand preference and hand skill in relation to sex hormones




Finger-length patterns and sex differences to sex hormones


Uner Tan Syndrome (habitual quadrupedalism + impaired cognition + cerebellovermial hypoplasia








Around 180 articles on spinocerebral motor control, intelligence, spinal and cerebral lateralization, sex differences in cognition and handedness in relation to sex hormones in men and women, finger-length patterns in relation to sex hormones, and Uner Tan Syndrome, published in periodicals included in Science Citation Index (1966-present), with nearly 2000 citations since 1966












Married four times with Nazife, Sezer, Sule, and Meliha


Four children:


Alper (35ya), Utkan (30ya) from Nazife and


Sevgi (14ya) and Sezgi (11ya) from Meliha










Violin playing since 1952, first violinist in Izmir Philharmony orchestra (1956-1960) and in  


      the Academic Orchestra of Goettingen University, Germany  (1960-1966).


Stamp collecting


Human and animal behavior


Select a payment method