TI:Unertan Syndrome/Revision

The Unertan Syndrome (UTS), first discovered by Tan in 2005 is characterized by three main symptoms: habitual walking on all four extremities; rudimentary intelligence with no conscious experience; and primitive language.

Cases

• Nine families exhibiting these symptons have been discovered, and so far all them are resident in southern Turkey, except for one who lives the northern Turkey region of Canakkale. The first discovered family lives 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.

• A second and third family have also been discovered in Adana. These families are also relatives. Two individuals within this family exhibit symptoms of UTS. Although there is no intrafamilial marriage, the pedigree analysis suggested an autosomal recessive transmission in these families.

• A very large family was discovered in Eskikonak(Gaziantep). There are six subfamilies within this large family, with intrafamilal marriages, and six individuals exhibiting UTS. These families also demonstrate autosomal recessive transmission .

Recently, Tan discovered a new series of families with individuals exhibiting UTS in a rural area of Canakkale in northern Turkey . The discovery of affected individuals in the Canakkale family suggest an autosomal recessive transmission, without intra-familial marriages. In all of these families, there are also bipedal ataxic individuals.

Analysis

The MRI scans showed a cerebellar and vermial hypoplasias in the affected individuals, except that in Adana Family, which showed only a mild vermial hypoplasia. 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 the chromosome 17p was affected in the first family resident in Demirkonak. Our collaborative studies showed that the affected individuals from other families have anomalies in different chromosomes (unpublished observations), suggesting a multigenetic origin of the TS.

A Brazilian family exhibiting UTS in all of the children born of a consanguineous couple was recently reported by Garcias et al. In accord with UTS, the affected individuals had qaudrupedal gait, severe mental retardation, and no language.

Symptoms

Walking style

The predominant symptom of UTS, is the quadrupedal gait. Nearly all of the individuals diagnosed stand up and maintain the upright position as long as they wish. Only a few of them are unable to stand up and maintain an upright posture. The main difficulty is the initiation of the necessary leg movement to take the first step using a leg. To do that, one has to maintain the body weight on the side opposite to the intended leg movement, i.e., to be able to stand onto one leg opposite to the leg intended to take a step, and vice versa. The truncal balance during standing is mainly controlled by the cerebellar vermis. However, the lateral balance during walking is different from the truncal balance during the upright posture..

The individuals have a normal sense of truncal balance during standing without any discomfort, but they lose balance if they try to take a step, transferring the body weight to the opposite leg and stabilizing it in an extensor position. The neural mechanisms of the bipedal gait are indeed very complex and not completely understood yet. The neural control of gait is not limited to the cerebello-vermial control systems.

The normal walking movements of the legs are indeed 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. A baby begins to move its legs as if stepping, while being unable to balance or support itself independently during stepping since the cerebellar and/or vermial systems needed to support the body during walking movements of the legs are not fully developed yet.

Lateral balance during upright walking may be referred to as asymmetric lateral balance and is instantaneously controlled by the spino-cerebro-cerebellar system in humans. If one compares quadrupedal walking in individuals with UTS against babies who make walking movements when held in the upright position, it can be concluded that the spinal walking movements with legs normally occur in individuals with 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 with 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, and vice versa in left-handers. Although the right-hand preference is a psychologic manifestation, it has neural mechanisms).

Accordingly, a preference for the qudrupedal gait should also have neural mechanisms. Walking on all four extremities in children is called bear crawling, which is normal in some children before walking on two legs. Children walking on all four extremities were 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 walk bipedally. Thus, there may be a transitory period during child development on which bear crawling is exhibited.

However, as seen in UTS, 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 with UTS is a developmental throwback. The normal(average) 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 staget, finding it quite easy, i.e., natural, to walk on all four extremities, as was habitually done by our ancestors.

Cognitive faculties

The intelligent actions were in a rudimentary level in the individuals with UTS. They could not answer 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),
• language and drawing (name a few items, repeat a sentence, paper folding, draw a watch).

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. 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 . The role of cerebellum in speech production has been reported frequently. Namely, cerebellar lesions may alter verbal expression and produce slow, monotonus speech that is not understandable , as seen in the individuals exhibiting the UTS.

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 habitual quadrupedality to habitual bipedality. 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

UTS cases are also interesting with respect to devolution. This is manifest in individuals with UTS as an experiment of nature. The term of devolution, originally used by Tan , 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 re-appeared in these individuals.

The UTS cases are the first examples of devolution in humans. An evolution in reverse or reverse evolution was previously used in some animal studies . According to ScienCentralNews(08.31.06), Capecchi said that

“we are trying to reconstruct what happened during the normal evolutionary process.”

Similarly, by studying humans with devolution in UTS exhibiting our most important ancestral trait, such as the habitual qaudrupedal gait, we can understand the mechanisms for the transition from habitual qaudrupedality to habitual bipedality, which most likely occurred by punctuated evolution 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”.