User:Uner Tan

Unertan syndrome
The Unertan Syndrome (UTS), first discovered by Tan in 2005[1] is characterized by three main symptoms: quadrupedal gait on all four extremities, rudimentary intelligence, and primitive language.

Contents
1 Cases

'''2 Analysis

3 Symptoms'''

'''3.1 Walking style

3.2 Cognitive faculties

3.3 UTS vs ancestoral traits

3.4 UTS vs devolution

4 References'''

Cases
Nine families exhibiting symptoms of the UTS have been discovered since the first one found in 2005; all of them are resident in rural areas of southern Turkey, except for one who lives in a rural area of Canakkale (northern Turkey). The first family is resident in Demirkonak (Iskenderun), and has 19 children that are now between 15 and 37 years of age. Five of them exhibit the symptoms of UTS. The father and mother are relatives, and as such the pedigree analyses suggest an autosomal recessive transmission[2][3][4].

A second and third family have been discovered in Adana[5][6]. Two individuals within this families exhibit symptoms of UTS. Although there is no intrafamilial marriages, the pedigree analysis suggests an autosomal recessive transmission of the UTS in these families.

Following the Adana family, a very large family is found in Eskikonak(Gaziantep). There are six subfamilies within this large family, with intrafmailial marriages, and six individuals with symptoms of the UTS. There were autosomal recessive transmissions in these families with UTS, too[7].

Tan recently discovered a new series of families with individuals exhibiting the symptoms of the UTS in a rural area of Canakkale in northern Turkey [8]. The pedigree analysis also suggests an autosomal recessive transmission, without intra-familial marriages.

Analysis
The MRI scans showed a cerebellar and vermial hypoplasias in the individuals showing the symptoms of the UTS. except one in Adana Family exhibiting only a mild vermial hypoplasia in his brain MRI. These results suggest that the main symptoms of the UTS may be caused by a vermial hypoplasia as a result of a chromosomal anomaly due to the autosomal recessive transmission. We have found that there was a defect in chromosome 17p of the first family resident in Demirkonak[9]. Our studies with a team from Bilkent University, Ankara, showed that the affected individuals from families resident in Demirkonak, Adana, and Eskikonak have anomalies in three different chromosomes (unpublished observations with Tayfun Ozcelik from Bilkent Un,iversity, Ankara), suggesting a multigenetic origin of the UTS. A Brazilian family exhibiting the symptoms of the UTS in all of the children born of a consanguineous couple was recently reported by Garcias et al[10]. Consistent with the symptoms of the UTS, the affected individuals showed a habitual qaudrupedal gait on all four extremities, severe mental retardation, and no language.

Symptoms
== Walking style ==

The main symptom of the UTS, is the habitual quadrupedal gait on all four extremities. Nearly all of the individuals diagnosed can stand up and maintain the upright position for a long time. Only one of them in Adana family is unable to stand up and maintain an upright posture. The main difficulty in the affected individuals is the initiation of the necessary leg movement to take the first step to start bipedal walking. To do that, one has to maintain the body weight on the leg opposite to the intended leg movement, and vice versa. It is well known that the truncal balance during upright posture is mainly controlled by the cerebellar vermis. However, the lateral balance during walking, i.e., to maintain the body weight on the leg opposite to the moving leg, is different from the truncal balance during the upright posture[11].

The normal walking movements are possible with a normal spinal cord without any interference from the supraspinal centres. This can be demonstrated when a baby is held upright with the feet just touching the ground, while being unable to balance or support itself independently during stepping since the cerebellar and/or vermial systems are not fully developed yet. Lateral balance during upright walking may be referred to as asymmetric lateral balance and is controlled by the spino-cerebro-cerebellar system in humans. If one compares quadrupedal gait of the individuals with symptoms of the UTS with the babies making walking movements when held in the upright position, it can be concluded that the spinal walking movements normally occur in individuals exhibiting the UTS while walking on all four extremities, even though they cannot manage the necessary postural adjustments during upright bipedal gait, thus the problem with asymmetric lateral balance.

All of the individuals exhibiting the symptoms of the UTS can walk on all four extremities with great ease, as if it is their natural gait. They therefore likely have a preference for the quadrupedal gait, similar to the psychological variable of hand preference: a right-handed man can write using the right hand with great ease, contrary to the left hand which is very clumsy in writing. Therefore he may prefer his right hand in writing; vice versa in left-handers. Although the right-hand preference, as a preference, is a psychologic manifestation, it has indeed neural circuits responsible for the preference to wright with the right hand in right-handers, and the şeft hand in left-handers.

An individual preference for the qudrupedal walk on all four extremities should have neural mechanisms similar to hand preference. Some children normally walk on all four extremities (bear crawling) before standing up and walking on two legs. Children walking on all four extremities are described thoroughly as early as 1928 by Hrdlicka, who reported 11 children walking on all four extremities for about eight months and then standing up and starting to habitually walk on two legs[12].

Thus, there may be a transitory period during child development on which bear crawling is normal. However, some children may prefer bear crawling for the rest of their life and continue to walk on all four extremities. Apparently, the human quadrupedal gait seen in adults exhibiting the UTS may be considered as a developmental throwback. The normal development of a child, probably following the evolutionary plan in the child’s genes, may have stopped at a point of transition from quadrupedality to bipedality. To be able to progress from a quadrupedal gait, a relatively older walking style, into a newer walking style such as bipedal locomotion, the evolutionarily newer cerebro-cerebellar systems regulating asymmetric lateral balance for upright walking should be developed in children. If not, these children would remain at the older evolutionary stage, finding it quite easy, i.e., natural, to walk on all four extremities, as was habitually done by our ancestors.

Cognitive faculties

The cognitive abilities are in a rudimentary level in the individuals exhibiting the UTS. They could not answer even a single question from the Mini-Mental State Examination Test adjusted for uneducated Turkish people. This test attempts to measure the patients capabilities in five fields: orientation (date and location), registration (immediate recall of three words), attention and calculation (count backwards), recall (recall three items), and language (name a few items, repeat a sentence)

The patients always had zero scoes in this test, except one who had 2 points from a total of 30 points. Concerning the language, the individuals with UTS from the first family used a language with very limited vocabulary, while the others from the remaining families could not speak at all, using only a few sounds to express their everyday wishes. A disordered cortico-cerebellar system may explain the cognitive impairments in UTS individuals, as associated with the cerebellar cognitive affective syndrome[13]. The severe mental impairments observed in individuals with UTS may be accounted for by the disruption of the cerebro-cerebellar circuits involved in cognition. The cerebellum has reciprocal connections with the left inferior frontal gyrus and the left lateral temporal cortex [14]. With regard to the role of cerebellum in speech production, it has been been reported that cerebellar lesions may alter verbal expression and produce slow, monotonus speech that is not understandable [15], as observed in the individuals exhibiting the symptoms of theUTS.

'UTS vs ancestoral traits'

The individuals with UTS exhibited ancestral features, such as walking on all four extremities with primitive or no language and rudimentary intelligence. Most of them had no language skills whatsoever, answering simple questions with a simple sound. Finding the gene or genes responsible for these uncestral traits may illuminate the mechanisms, for instance, for the transition from our quadrupedal ancestors to our bipedal ancestors. Studying the fossil records have not been successful in this respect. Indeed, we now have live models to study the human evolution, especially with regard to the much discussed transition from the habitual quadrupedal walking on all four extremities to the habitual bipedal walking on two legs. Herein, there has been no intent to insult or injure these individuals affected by UTS, rather this is an endeavor to better understand the mystery of human evolution.

'UTS vs devolution	'

The individuals exhibiting the UTS may be interesting with respect to human evolution. The reappearence of the ancestral quadrupedaily in UTS cases may be considered as a human devolution, which is manifest in individuals with UTS as an experiment of nature. The term of devolution, originally used by Tan [16][17], with respect to the evolutionary direction of human beings, merely means a reappearance of an earlier trait, such as the reappearance of the habitual quadrupedal gait in some human beings. As a result of nature’s experiment, UTS with ancestral features may have been re-appeared in the UTS cases, which are the first examples of devolution in humans. Similerly, an evolution in reverse or reverse evolution was previously shown in some animal studies [18][19][20]. According to ScienCentralNews (08.31.06), Capecchi said that we are trying to reconstruct what happened during the normal evolutionary process. Accordingly, by studying humans with devolution we can understand the mechanisms for the transition from habitual qaudrupedality to habitual bipedality, which most likely occurred by punctuated evolution[21] resulting from a genetic mutation, provided that we can determine the location of the gene or the gene pool responsible for the quadrupedal gait in humans with UTS. This is apparently contrary to Darwin’s theory of gradual evolution. If the Darwin’s theory of gradual evolution would be correct, all of the monkeys would have started to walk bipedally long ago, at least imitating man. To elucidate the genetic mechanisms of the transition from quadrupedality to bipedality in human beings would be a groundbreaking scientific development in human history. Therefore, there is no reason to be insulted or suggest injury by the “Unertan Syndrome”.