Genes and genetic disorders

If we think about how amazing it has been  the Human Genome project, how much we have learned from it and everything that has been generated so far, it's impossible to ignore the value of genomics, for example,  initially was thought that our 46 chromosomes were composed of 100,000 protein-coding genes, enzymes, hormones and overall regulatory sources of all life processes that shape human characteristics but now is possible to begin to manipulate all of them  to heal syndromes and diseases.

Chromosome 22 was the first to be fully identified 545 genes having assets, followed later by genetic mapping or sequencing of chromosome 21, with only 225 active genes, which opened the possibilities for genetic treatments medical situations as Down Syndrome, a form of Alzheimer's disease and various cancers.

Thus began the race to find a specific gene for each of the major conditions that afflict humans. At the same time, it have been found the relationship between the production of proteins and some genes that create on protein production and others that inhibit the production of the same.

In this sense it was found some genes associated with autism spectrum syndromes such as 15q11-q13, 2q37.3 or UBE3A for Angelman syndrome, which has also been associated with the GABRB3 gene, whereas for the syndrome Williams is the gene 7q11.23; MeCP2 for Rett syndrome, to mention only the best known developmental syndromes.

However, it is known that there are more syndromes, such as West syndrome that is associated with the ARX gene, or even lower prevalence may be mentioned De Lange syndrome or Crohn's disease, whose genetic alteration is in 5p13.1 gene.

Talking about less common syndromes we can talk about Smith-Magenis syndrome which is associated with  17p11.2 gene, or the VCFS 22q11 gene related, with myotonic dystrophy which is a multisystem disease whose genetic alteration is associated with the repetition CTG trinucleotide on chromosome 19.

While the tuberous sclerosis complex (TSC), which is an autosomal dominant inherited disease which may be due to the mutation of two distinct genes: TSC1 (9q34) and TSC2 (16p13.3).

Timothy syndrome caused by a mutation in the gene CACNA1C located in 12p13.3, other forms of alteration as 10p terminal deletion, has been associated with a phenotype similar to DiGeorg syndrome causing hiccups hyperparathyroidism, deafness sensory abnormalities stones.

Moreover, it has been  studied the gene involved with 45X/46XY mosaicism, or we can mention Cowden syndrome is associated with PTEN gene, which is located at 10q23.3.

Another group of genetic disorders like Goldenhar syndrome are related  to deletion 5q (Artigas-Pallares, Gabau-Vila & Guitart-Feliubadaló, 2005), all associated with developmental disorders.

Whereas if you look at the studies on cancer have been found, for example for brain cancer, NFkB protein with much higher activity than in normal brains or HER2 protein in lung and breast cancer, BCR- AB1 for chronic myelogenous leukemia, RAS, for several types of cancer, B-RAF for skin cancer, BCL-3 for lymphoma; RB1 for retinoblastoma, HNPCC for colon cancer and endometrial, the p53 gene causes cell suicide and is associated with cancer of the lung, colon, breast and brain (Collins and Barker, 2008).

It's not possible to forget disorders of cognitive processes such as Alzheimer's,  so it's possible to find genetic associations with cognitive processes, although further studies are not conclusive, for instance mentioned the IGF2R gene associated with intelligence, which is a very popular topic.

That is why around 1980 Dr. Plomin, from Institute of Psychiatry, at London, England, began his research on genes and intelligence relationship, since observed that two people with the same genes correlate as much as the same person performing an intelligence test with a year of difference, so he realized that identical twins who live apart are very similar or identical in intelligence tests that identical twins who live together, which is why it is considered that the environment influences the development of children, however it has become clear that genes can shape the brain in ways that make individuals better or worse to answer an intelligence test.

Despite this, Plomin suspect that more markers are needed to find the genes for intelligence, but states that exist many difficult to replicate details to affirm conclusively that have these genes (Silverman, 2008).


More consistently it was found the  called language gene, which from the genetic standpoint is associated with the specific disorder of the cognitive process, which seems to be due to alteration of a small number of key genes and in particular FOXP2 gene mutation.


The gene in question is expressed primarily in certain areas of the central nervous system, both during embryonic development and in the adult individual, but is also expressed in other regions during embryo development, such as lung, intestine and heart, and in different tissues of the adult. However, affected individuals with language impairment, have a non-mutated copy of the gene (Burraco Benitez, 2005; 2006; Gopnik and Crago, 1991).


Although each day is more advanced in the study of genes and the proteome, considering that it is estimated that there are about 4000 genetic disorders, and so far has been identified only a little more than 60 genes involved in diseases, no doubt the work will take several years before conclusion, but in spite of all the implications of research some point that knowledge of the human genome will be the main focus in the diagnosis and treatment for a large number of diseases such as diabetes, cardiovascular disease, mental and many forms of cancer.

References: 

Artigas-Pallarés, J., E. Gabau-Vila, E., Guitart-Feliubadaló, M.  (2005) El autismo sindrómico: II. Síndromes de base genética asociados a autismo. Rev Neurol. 40 (Supl 1): S151-S162.

Benítez – Burraco, A. (2006) Genes y lenguaje. Teorema Vol. XXVI/1, 37-71.

           

Benitez-Burraco, A. (2005) FOXP2: del trastorno específico a la biología molecular del lenguaje. I. Aspectos etiológicos, neuroanatómicos, neurofisiológicos y moleculares. Rev Neurol.  40 (11): 671-682.

Collins, F. and Barker, A. (2008) Mapping the cancer genome. Scientific American Special Edition: New answers for cancer. Vol. 18. Num. 3. 22-29.

Gopnik, M. y M. B. Crago (1991) Familial aggregation of a developmental language disorder.  Cognition. 39. 1-19.

Hayden, KE., Strome, ED., Merret, SL., Lee, HR., Rudd MK., Willard, HF. (2013) Sequences Associated with centromere competence in human genome. Molecular and Cellular Biology. 33 (4) 763-772.

Weischenfeld, J., Symmons, O., Spitz, F.,&  Korbel, J. (2013) Phenotypic impact of genomic structural variation: insights from and for human disease. Nature Reviews Genetics. 14. 125-138.

 Young, E. (2013) Shutting down the extra chromosome in Down's Syndrom cells. National Geographic: Phenomena: Not exactly rocket science. Disponible en: http://phenomena.nationalgeographic.com/2013/07/17/how-to-shut-down-the-extra-chromosome-in-downs-syndrome/

Autism spectrum disorders: a detection of abilities and not dis-abilities.

I found once a quote which is supposed was written by Volkman and Cohen and it says: “If all individuals diagnosed with autism could be together in a room, the most striking fact would not be their similarity, but how different they are between them". And I would like to  add: and if at the same room we can  join all therapists and people who do not live with children with autism  every day, them it would be very easy to see what children cannot do, but only a few would be able to admire their skills.

I learned the word autism more than 20 years ago during my work in a children's hospital in Mexico. Those days, the diagnosis was confused with psychosis and not many persons spoke so publicly about the topic. The only therapeutic proposed was medications that maintain quiet to children and if at home behavior and socialization did not work, then the only one answer was a hospital. There were some behavioral therapies that were used with a few children, but the therapeutic goal was to keep them quiet.

Nobody spoke too much, at least in Mexico,  of other developmental disorders such as syndrome fragile X, Rett syndrome, the Prade Willi syndrome, childhood disintegrative disorder, tuberous sclerosis, Williams syndrome, Angelman's syndrome or Asperger's syndrome, and if anything was said something of the autism spectrum disorders, the only one word was autism.

In contrast, Autism Speaks is currently an international voice that gives help to autism children and families and their numbers reported that 1 in every 88 children has autism diagnosis at the United States. 

Certainly there is extensive information now. On the internet when someone types the word autism appear at least 9 860 000 results. But there is still something on the entire set of signs and symptoms that children have and that every parent knows so well. Something that every site, campaigned and paper, sometimes forget: we started to talk about autism and we forget the children and the people behind it. 

As experts we can’t hide our perplexity, because the autistic spectrum has a variety of features, even though they have tried to group into versions of the DSM and ICD, there is always a child that presents all the symptoms and none of the above.

At a conference held in the CISAME in 2010, once all the experts talked with passion about what each of us we have studied about the disorder, a girl of 8 years raised her hand. I think we all ignore it for a few moments, and it was not we did not see her, but there were more hands trying to ask those things we wanted to share, so she raised her hand higher, to the point that we all thought that she would jump on the person near to her to get our attention. We finally gave her the word and with reverence asked us: "why do you speak about autism?" before autism I am a girl when will you speak about children with a diagnosis of autism? ".

She was my motor and I started to write about what it’s possible, all the things any child can with or without  developmental disorders, the reason why so many  experts have sometimes spent a lifetime saying loud and strong things beyond the word autism, and even beyond all behaviors that have caused distress to the parents, or the moment when they receive the diagnosis, much more than the long list of No that parents and children here every day: they cannot talk, you cannot write, they cannot go to school, they  cannot dance, they  cannot go to College, they cannot make anybody smile, do not, do not not. 

Don’t they breathe?, perhaps don´t  they grow?, let’s go slowly.

Looking for evidence

More than 50 years ago was suspected that autism is linked to a specific gene. At least 17 candidate genes linked to the disorder to varying degrees and in different ways have been reported so far, he points to others who may have incomplete information or translocate. That's why there is more research with families who have more than one child with a diagnosis of autism, but so far, there is not a single research that points to a single gene.

Even those development disorders such as the fragile X or Rett syndrome, where there are a limited number of genes responsible for all the symptoms, can show variations in the development of the children and there were found mutations or genetic drafts that do not tie in all cases. That’s one reason why unique children can be found, children who have more skills than ICD show in its pages.

On the other hand, mirror neurons have been mentioned as responsible for the difficulties in socialization and empathy, however, some children "learn" to socialize depending on environmental conditions.

Vaccines were during some years claimed as responsible of autism, but it has already proven that they are not guilty of triggering, and even better all the story was an invention.

A new group of evidence show than the virus HHV-6 can be part of some cases, but there is only few articles about it.

And I can continue mentioning factors, from environmental, family, social, and even cultural, but no matter how much time you can take to try to explain the causes of autism spectrum disorders, the truth is that the great needremains to help children and their families to have a more happy life.

And following my passion about the brain and trying to find answers where the disorder originates, I began to look for answers, trying to see what everyone sees, that no one looks. 

All studies point out about all the neuro degenerative aspects and brain differences, particularly in the white matter, which are the nerve fibers, myelinated responsible for the transmission of information from one cell to another. Differences in the amount of gray matter that is the neural bodies and dendrites devoid of myelin have also noted. With this in mind, there is no doubt autism is a neural problem.

I’ll stop for a second to say that for many years researches know that the brain is plastic, moldable, flexible and it adapts to environmental emergencies. This feature is probably given by evolutionary aspects, what you have may change with the passage of the years. And although many generations are required to see a general shift to level species, if it is possible to see brain differences from various learning tools. 

In the case of normal development, even the brain does not know what kind of environment must adapt, the plasticity allows to babies to develop those skills that will be used in the environment. Those actions can make him or her feel happier, those that will be reinforced, to speak, walk, and smile. This usually this reminds me an old question: Is an artist born or made?. 

The answer that I like most is that perhaps all of us concert pianists, but we never had the opportunity to beat a piano.

For example, it’s known that even though children are able to recognize foreign languages, they will lose this ability to give priority to the native language, finally it is that is going to provide an effective socialization. This is clear that neurons survive depending on usage. 

It seems that nature has very clear use of resources and their exploitation, by what is not the luxury of having neurons which does not use, and will maximize those that serve as tools in response to the environment.

The brain with developmental disorders

Under this principle of plasticity, the idea is that the neurodegenerative process apparently happens even before the first symptoms, but to the passage of the cerebral arrangement, imprisons areas that are losing connections and that imprisonment, and eventually becomes little used. However, there are other areas that manage to survive and become efficient, much to its way.

If every child had deficiencies such as are indicated by the diagnosis books, it would be easy to diagnose the disorders, however, it seems to me that it is not. Even for experts, it is easy to confuse the symptoms. For example, in a study conducted in the Autism clinic of CISAME, in Mexico city, it was found that 27% of cases should not be diagnosed as part of the autistic spectrum, because the clinical histories revealed perinatal problems as causes of the symptoms and signs of children.

That’s why I prefer to invite parents to analyze: what children can do?. The main symptom is focused on the shortcomings of communication, but even in children who do not speak show means of expression. This is the case of Carly Feischmann, who had never said a word, until by chance, his parents and therapists discovered that she was able to write on a laptop and that opened the door to communication.

But, what else can your child do?, if you search you will find that your child can do things, not like the others, perhaps  he or she does things with a special nuance, perhaps so sophisticated as the protagonist of the series, Touch, or much to his or her own way. Even maybe she or she smiles with that expression of a few friends, but for you, without place to doubt is a smile.

On the basis of brain plasticity, don't give up, your child's brain will adapt to circumstances, perhaps slower and not as high, and rightly so as other children. But if support you, there is no doubt that surprise.

Perhaps the rule is not to see him with pity, that feeling of disability is destructive, it makes us think that you can't, you don't know, that not this and not the other. Try, do it twice, three, four. How the Olympic athletes get so amazing victories?, they do the same movement over and over again until they can  make it perfect. It’s worth the attempt.

Finally, would like to recall that no brain is equal to another, that all we learn, feel and see the world in different ways, that's why I do not understand, and I would admit my ignorance, I don't understand the why focuses attention on what children cannot be achieved, as if genetics or disorder destination, if there are many evidence of brain plasticity and achievements perhaps small for humanity, but who become great strides of each child with any developmental disorder. Despite the difficult thing is sometimes deal with their tantrums.

I think that scientist, parents, and society must work in the understanding of disorders, not to ask for money, not for gain notoriety or be at the front of the photo, but to give a chance for adaptation to children, who one day will grow and become adult.

The big mistake is to ask that society adapts to them, asks to parent to stop their lives to one side for the sake of their children. One day the parents won’t be around to look after that child, so the goal is adaptation and not the adequacy.

Skills

Without falling into the trap that all children are like the books, I can say that several researches find math skills, music, the visual Arts, as the most reported, but, have tried to give your child a computer or a tablet computer?, maybe help you at the garden?, maybe the macrame is a choice... those who have in addition a little or a lot of obsession compulsion can be excellent for quality control. 

I would say, don’t think in them as the persons who can do nothing, find that they can do, and you will find the talent. The goal is to find what they can do. Even the blind deaf child can feel and smell and that can be enough to discover the world.

And for those who have brothers, enforces the same. My goal in education is that children can find their talent as young as possible so they can be happy children and successful adults. Perhaps a skill as an adult is to find the gift of each one of these children. Achieve communication, by any way is worth. I'm sure you'll be amazed of what you can  find. 

Being a child with autism is not a diagnosis, it is a tag of life, but most importantly, YOU have a life to decide what to do with it. They just need someone who provides one hand to achieve this.

Alma Dzib Goodin

If you would like to know more about my writing you can visit my web site:
http://www.almadzib.com

References:

Artigas-Pallarés, J. (2001) Las fronteras del autismo. Revista de neurología clínica. 2 (1) 211-224.

Blaxill, MF. (2004) What’s going on? The question of time trends in Autism. Public Health Reports. 119. 536-551.

Belcastro, ML., Mastoianni Pinto, S., Calcagno, M., Salomón, F., y Marengo, R. (2007) Trastornos del espectro autista y déficits auditivos. Arch, Neurol. Neuroc. Neuropsiquiatría. 13 (1) 73-77.

Carvajal-Molina, F., Alcami-Pertejo M., Peral-Guerra, M., Vidriales-Fernández, R., y Matín-Plasencia, P. (2005) Datos neuropsicológicos de niños con trastorno autista y desarrollo intelectual en el intervalo considerado normal. Revista de Neurología.  40 (4) 214-218.

Dirk de Jonge, D. (2009) Autistic Number Learning: what autism can tell us about acquisition of numbers concept. Thesis, MS in Logic. Universitiet van Amsterdam.

Dykstra, JR., Boyd, BA., Watson, LR., Crais, ER., and Baranek, GT. (2012) The impact of the Advancing Social-communication and Play (ASAP) Intervention on preschoolers with autism spectrum disorder. Autism. 16 (1) 27-44.

Dzib, A. (2010) Alteraciones del desarrollo por dificultades perinatalas y la confusión con los trastornos del espectro autista. Revista Mexicana de Neuro Psicología. 5 (1) 4-9.

Dzib Goodin, A. (2012) Comprendiendo las diferencias cerebrales para la educación del talento. Disponible en red: http://neurocognicionyaprendizaje.blogspot.com/2012/02/comprendiendo-las-diferencias.html

Hernández, JM., Artígas-Pallarés, J., Martos Pérez,J. Palacios Antón, S., Fuentes-Biggi, J., Belinchón Carmona, M., Canal-Bedia, R., Diez Cuervo, A., Ferrari-Arroyo,MJ., Hervás-Zuñiga, A., Idiazábal- Alecha, MA., Mulas, F., Muños-Yunta JA., Tamarit, J., Valdizán, JR., y Posada De la Paz, M. (2005) Guía de buena práctica para la detección temprana de los trastornos del espectro autista. Revista de Neurología. 41 (4) 237-245.

Muhle, R., Trentacoste, SV., and Rapin, I. (2010) The genetics of Autism. Pediatrics. 113 (5) e472-e482.

Narbona, J., and Patiño, A. (2002) Estudios genéticos de los trastornos de comunicación. Revista de Neurología. 35 (1) 32-36.

Pierce, K., Müller, RA., Ambrose, J., Allen, G., and Courchesne, E. (2001) Face processing occurs outside the Fusiform “face area” in autism: evidence from functional MRI. Brain. 124. 2059-2073.

Rodríguez, F. (2009) Aspectos explicativos de comorbilidad en los TGD, el síndrome de Asperger y el TDAH: Estado de la cuestión.Revista chilena de neuropsicología.  4 (1) 12-19.

Ruggieri, V., y Arberas, C. (2007) Trastornos generalizados del desarrollo: Aspectos clínicos y genéticos.  Medicina. 67 (1) 569-585.

Wolff, JJ., Gu, H., Gerig, G., Elison, JT., Styner, M., Gouttard, S., Botteron, KN., Dager, S., Dawson, G., Estes, AM., Evans, AC., Hazlett, HC., Kostopoulos, P., MCKinstry, RC., Paterson, SJ.,  Schultz, RT., Zwaigenbaum, L., and Piven, J. (2012)  Differences in White matter fiber tract development present from 6 to 24 months in infants with autism. American Journal of Psychiatry :.10.1176/appi.ajp.2011.11091447