Arxiu d'etiquetes: syndrome

Williams Syndrome: musical geniuses

Williams syndrome affects 1 in 20,000 new-borns, and it is considered a rare disease. It is said that people affected have a gift for music. You can learn about this syndrome and know their music relation in the following article.


This syndrome is called with several names: Beuren syndrome, Williams-Beuren syndrome, Elfic traits syndrome, supravalvular aortic stenosis and hypercalcemia syndrome… These names are related with their discoverers or their clinical features.

It is included in microdeletion and microduplication syndromes. A microdeletion is the loss of a small piece of a chromosome. This piece can be smallest and it can hinder its microscopic observation. Microdeletions are related with microduplications because the lost piece which causes a microdeletion is joining another chromosome. So, it causes a microduplication.

There chromosomic rearrangements are due to LCRs (Low Copy Repeats), it means big similar blocks, which are formed by duplication of pseudogenes (genes without defined function) or repetitive DNA inside the specific chromosomic region.

Microdeletions usually measure 1 to 3Mb of length, and involve several contiguous genes. The size and location of microdeletion that cause a syndrome can change, but specific critic region is always involved.

The gain of material produces a slight phenotype, then there are people affected by microduplication, but they do not have some characteristic features like in the microdeletion.


The phenotype is slight. They have a mild or moderate intellectual disability, and their intellectual quotient (IQ) is 50-65.

They have similar facial features. These features include a low nasal bridge (Figure 1), small upturned nose, long philtrum (upper lip length) and wide mouse.

puente nasal
Figure 1. Comparison between standar nasal bridge and low nasal bridge (Source: Keck Medicine of USC)

They also have an elastin deficit, which produces anomalies in connective tissue. The majority part of medical problems are due to supravalvular and pulmonary aortic stenosis, narrowing blood vessels.

They suffer hyperacusis (sensitive hearing). However, they are great musicians and have facility for learning musical language. The delay in the language’s development can later convert into loquacity and a strong capacity to learn by listening.


Williams syndrome’s microdeletion is produced in chromosome 7q11.23 and is flanked by LCRs with sequence identity higher than 97%. Sequence identity makes the blocks susceptible to non-allelic homologous recombination (NAHR), producing translocations, inversions and deletions or/and duplications (Figure 2).

Figure 2. Non-allelic homologous recombination where a deletions and duplications between chromosomes are originated. Red boxes and arrows indicate location and orientation of LCRs (Source: G. Kirov, 2015)

Although Williams syndrome is considered an autosomal dominant disorder, in most cases microdeletion is not inherited, but it is de novo.

More than 90% cases there is a deletion of 1.55Mb of DNA. This deleted part includes 26 genes. 5% corresponds to a deletion of more bases, producing a deleted fragment of 1.8Mb and 28 genes. It is atypical to find other deletions, however there are cases. All cases include ELN gene (elastin gene), which forms part of Williams syndrome critic region (Figure 3).

Figure 3. Williams syndrome critic region (WSCR). In red are marked all posible deleted fragments, which can origin the syndrome (Source: B. R. Pober, 2008)

Deletion of an elastin gene allele is identified as Williams syndrome’s cause. There is a clear genotype-phenotype correlation, where elastin gene is responsible for connective and vascular tissues defects. Actually it is studying other genes, but there are not enough studies which strengthens a correlation between observed phenotype and these genes.


People affected by Williams syndrome have an entirely normal life. Cardiovascular conditions can cause worse clinical signs, but with medications, if it is necessary, they are not a disadvantage.

Still more has to be improved, but the integration into society of people with a lower intellectual deficit to the median is quite good.

Figure 4 shows the draw and explanation of elephant by a 18-year-old girl affected by Williams syndrome, with 49 IQ.

Figure 4. Contrast between visual-spacial and language abilities of a 18-year-old girl with Williams syndrome and 49 IQ. (A) Draw of an elephant (B) Explanation of an elephant (Source: Wang, 1994)

They have very specific weaknesses in visual motor integration, which are those that cause intellectual disability, but with a certain preservation of language and other activities (sociability or empathy).

In spite of these weaknesses, they are considered great musicians. Following there are two examples of those affected by Williams syndrome with talent for music.

Gloria is not able to tie her sneakers, but she has learned to sing songs in 30 different languages (Video 1).

Video 1. Gloria Lenhoff, soprano soloist of a choir (Source: YouTube)

Jim works at Disney World playing the piano. Despite his low IQ, he has taken a lot of agility by playing the piano and only hears a melody once he is able to play it (Video 2).

Video 2. Jim playing the piano. In minute 1:40 he makes a turn and starts playing faster without obstacles (Source: YouTube)



Abrahim’ story: the child with 3 people’s DNA

On last 27th September media echoed with the news of the first birth of a child with DNA from three people, through the experimental technique, called spindle nuclear transfer. What is this technique? Is it possible to have DNA from other people besides our parents? Then, I will explain the news in detail.


We need to know well his parents. They are a couple from Jordan, whose wife is a 36-year-old woman with a gene mutation in her mitochondrial DNA. It is right: mitochondrial DNA. A part of the nuclear DNA, where is found in our cell’s core and we currently mean, there is also DNA in our mitochondria. Mitochondria are double membrane-bound organelles found in all eukaryotic organisms and play a crucial role in energy production. They are necessary for our cells breathe and produce energy.

Like nuclear DNA, mitochondrial DNA can suffer mutations caused inherited diseases. For example Leber’s hereditary optic neuropathy (LHON), a rare inherited disease that causes blindness due to degeneration of the optic nerve.

Well, the mutation suffered by the protagonist of the story in their mitochondrial DNA cause Leigh syndrome. It is an early-onset progressive neurodegenerative disorder with a characteristic neuropathology consisting of focal, bilateral lesions in one or more areas of the central nervous system, including the brainstem, thalamus, basal ganglia, cerebellum, and spinal cord. Clinical symptoms depend on which areas of the central nervous system are involved.

Mitochondria are inherited only from mothers, a pattern known as maternal inheritance. This is the reason that they need to find a solution and avoid to transmit mitochondrial DNA (with mutations) to offspring. Previously, she had 4 pregnancy losses and 2 deceased children at age 8 months and 6 years from Leigh syndrome. The percentage of mutant DNA in mother’s mitochondria is enough for her to have no symptoms of the disease and only be a carrier. However, the probability of transmitting the mutation to offspring is very high.


The couple sought out the help of John Zhang and his team at the New Hope Fertility Center in New York City. They work researching techniques to prevent diseases caused by mutations in mitochondrial DNA.

Currently, there are two methods for mitochondrial replacement: pronuclear transfer or transfer of the mitotic spindle. In both cases a donor is needed, who has not any mitochondrial DNA mutation.

The first technique is called pronuclear transfer (Figure 1) and involves fertilising both the mother’s egg and a donor egg with the father’s sperm. Before the fertilised eggs start dividing into early-stage embryos, each nucleus is removed. The nucleus from the donor’s fertilised egg is discarded and replaced by that from the mother’s fertilised egg.

But this technique wasn’t appropriate for the couple for religious reasons (they are Muslims). And this method involves the destruction of two embryos.

Figure 1. Pronuclear transfer. An egg from the mother (yellow) and an egg from the donor (purple) are fertilized with sperm from the father (yellow). When the pronucleus is formed in each egg, its is eliminated from the donor and the mother’s pronucleus is inserted in the donor’s egg (Source: A Scientist’s Guide to Making Babies…)

So Zhang’s team took a different approach, called spindle nuclear transfer (Figure 2). They removed the nucleus from one of the mother’s eggs and inserted it into a donor egg that had had its own nucleus removed. The resulting egg (with nuclear DNA from the mother and mitochondrial DNA from a donor) was then fertilised with the father’s sperm.

Figure 2. Spindle muclear transfer. The red egg corresponds to the mother, and her mitotic spindle is removed and inserted into the donor’s egg (orange), which previously has been extracted her mitotic spindle. Later, the egg is fertilized with sperm from the father (blue) (Source: Revista Genética Médica, modification)

In either methods the new egg is 100% free of maternal mitochondrial DNA (mitochondrial DNA with mutations) because it is estimated that about 1% of the mitochondrial DNA can be entrained with the nuclear genetic material. However, it is considered that the levels are low enough to cause Leigh syndrome.


The procedure is not legal in the United States, so it was done in Mexico, where rules around human embryo manipulation are more lax than in the United States, which has declined to greenlight the experimental procedure.

The technique has gained notoriety because it leaves the baby with three genetic parents. But there is a part of the scientific community that is not quite agree because he fears are not complied with all ethical codes. The limited information in the abstract left many wanting more.

Zhang’s team created 5 embryos and only one had a normal karyotype (46,XY). It was implanted into the mother and 9 months later Abrahim was born (Figure 3). He is a boy and there is no risk to transmit his mitochondria (donor’s mitochondria) to his offspring.

Now, this Jordanian family enjoys their healthy baby at home, and for the moment the mutation was detected in less than 1% of mitochondria

Figure 3. Fertility specialist John Zhang with the newborn baby Abrahim (Source: Science)



Marfan syndrome: how to live of a rare disease

What they have in common the American president Abraham Lincoln, the Greek painter El Greco or the Spanish actor Javier Botet? All of them had or have Marfan syndrome. This is included within rare diseases (less of 1 case per 2,000 inhabitants). In this article I will explain what happens to people who suffer Marfan syndrome, and also one example of people affected and how he has taken advantage of his syndrome.


Marfan syndrome is a rare disease of the connective tissue, it means the tissue that spreads throughout the body and its mission is to join the tissues, fill the gaps between organs…The connective tissue is found in all the body, and the Marfan syndrome’s patients have various problems in multiple organs (bones, eyes, heart, blood vessels, nervous system, skin and lungs).

Its name comes from the French doctor Bernard Jean Antoine Marfan that, in 1896, detected the case of a 5-year-old girl who had disproportionate long arms in relation to her body and finger very thin and long.

It is included within rare diseases because it affects 1 in 5,000 people. A rare disease is one that affects a small number of people compared to the general population.


The clinical features can be grouped mainly in skeletal system, cardiovascular system and ocular system.

The characteristics of the skeletal system are the most visual and among them we find (Figure 1):

  • Dolichostenomelia: disproportionality long extremities in comparison with the length of the trunk. It implies that people are taller than would be expected from their genetic background.
  • Arachnodactyly: thin and long fingers, like spider’s legs.
  • A high, arched palate and crowded teeth.
  • Scoliosis: an abnormally curved spine (S or C).
  • A breastbone that protrudes outward (pectus carinatum) or dips inward (pectus excavatum).
fig caract
Figure 1. A Marfan syndrome’s boy, where we can see pectus excavatum, dolichostenomelia and arachnodactyly (Source: National Marfan Foundation)

The features of cardiovascular system are the main source of morbidity and early mortality. Dilatation of aortic artery is the most common and serious, but also we find tear and rupture of the aorta, mitral or tricuspid valve prolapse…

Finally, within ocular system we have ectopia lentis (a displacement or malposition of the eye’s crystalline lens from its normal location) or myopia. There is also a high risk of retinal detachment, glaucoma and early onset of cataracts.


Marfan syndrome is caused by a change in the gene that controls how the body makes fibrillin (FBN1), an essential component of connective tissue that contributes to its strength and elasticity. This gene is located in chromosome 15 and the severity of the disease depends on the affected part. It means that there aren’t two identical types of Marfan. There are some people who have physical traits more pronounced, and this facilitates the diagnosis. But there are other people that who do not show outward signs.

It has an autosomal dominant inheritance; it means that an altered allele is dominant over the normal allele and it only needs a copy for expressing the disease. It appears in all generations and a child of an affected parent has a 50% probability of suffering this syndrome. However, it can also occur by de novo mutations in the gene FBN1 (spontaneous mutations). The probability of these mutations is low and it is presented in 25% of all cases of Marfan syndrome.


As in most rare diseases there is no treatment, but it can alleviate pain and symptoms caused by the syndrome.

Complications have to anticipate and prevent. The treatment is to act on the cardiovascular effects, mainly to avoid the risk of dilating the aorta.

Doctors do regular cardiological tests, repair or replace large vessels, replace of heart valve, do rehabilitation and orthopedic tests to minimize scoliosis and avoid contact sport.


Throughout history many famous personalities have suffered Marfan syndrome. The tendency of painting elongated humans of Dómenikos Theotokópoulos “El Greco” was due to Marfan syndrome. But it is not the only case known, the musician Niccolò Paganini or the member of the band The Ramones, Joe Ramone, also had it.

Depending on the genetic disease that people suffer, it can be difficult to live with it. But there are some people who have managed to take advantage of it.

This is the case of the Spanish actor Javier Botet. He is known for his role as the Medeiros’ girl in Rec (Jaume Balagueró and Paco Plaza) or mom in Mamá (Andrés Muschietti), among others. His case is complicated, because he has undergone surgery five times. He has taken advantage of his appearance and physical characteristics to characterize diabolic characters (Video 1, not suitable for sensitive people!).

Video 1. Movement test of Javier Botet in Mamá (Source: YouTube)

The example of this guy shows us that we must always see the glass half full and turn the situation around.



21st March: world Down syndrome day

21st March is the World Down Syndrome Day. This syndrome is a chromosomal combination that has always been part of the human condition. It exists in all regions of the world, and usually it has variable effects on learning styles, physical characteristics or health. It affects 1 in 700 children, making it the most common chromosomal abnormality and the first cause of mental disability. With this article I want to introduce a little more this syndrome.


Its name comes from the English doctor John Langdon Down who described a group of patients with intellectual disabilities and similar physical characteristics, in 1866. These patients had Down syndrome.

However, already existed artworks with people with Down syndrome (Figure 1), but Langdon Down was the first one to group them in a subcategory within individual with cognitive impairment.

quadre oli
Figure 1. “The Adoration of the Christ Child” (1515). This oil painting, made by a follower of Jan Joest van Kalkar, shows two people with Down syndrome (Source: Arte y síndrome de Down)

It is called syndrome because the affected people express a known set of symptoms or signs that they may appear together, although its origin is unknown. Even though physical features are common, each person with Down syndrome is a unique individual and can present the characteristics in different degrees or not.


  • Diminished muscle tone
  • Small ears
  • Slanting eyes
  • Short nose
  • Flat back of head
  • Single crease in the palm of the hand: simian crease: complete fusion between heart line and headline (Figure 2)
  • Tendency to obesity
Figure 2. (1) Common lines, like M, and (2) simian crease, complete fusion between heart line and headline (Source: Incidencia de nacimientos pretérmino y de término con peso bajo al nacer y existencia de línea Sydney)

When they are children present retardation in reaching capabilities as sitting independently, wandering, first words…


In 1959, Jérôme Lejeune, a French doctor, saw that people with Down syndrome had 47 chromosomes in each cell instead of 46. This extra chromosome was 21 (Figure 3). The article  Why I look similar to my parents? reminds us what a chromosome is.

Figure 3. Male karyotype, person with Down syndrome (Source: Mireia Ramos, Cerba Internacional SAE)

So, Down syndrome or trisomy 21, is a result of an extra chromosome. But having and extra copy of chromosome 21 can be given by three phenomena.


It is the major cause and represents 95% of cases. It is produced by an error in the process of cell division. It means that when parent’s cell divides there is an error, and the son inherits two copies of chromosome 21 instead of one.

Then the son has 3 chromosomes 21: 1 comes from one parent and 2 come from the other parent, which are transmitted together.


During the process of cell division of one parent, a chromosome 21 joins with other chromosome, usually a chromosome 14.

Then the son has 3 chromosomes 21: one comes from one parent and two come from the other parent.

It represents 4% of cases, and it is important to identify it to avoid passing the translocation to another child, if the couple wants another child.


It is the least common cause because it represents 1% of cases. After fertilization nondisjunction occurs, but not in all cells. This causes cells with 46 chromosomes and cells with 47, forming a mosaic.

Cells with 47 chromosomes have an extra chromosome 21.


It has been found that the age of the mother is related to have a child with Down syndrome, i.e., the risk of having a baby with Down syndrome is greater among mother age 35 and older.

Trisomy 21 is the most trisomy accepted by nature, so in pregnancy test doctors always study it. If they detect a foetus has Down syndrome, the couple can choose to go ahead or to stop pregnancy.

People with Down syndrome are increasingly integrated into our society. Their IQ is 45-48, when the standard range is around 100, but with a special school integration support is highly beneficial and IQ can go up to 70.

Nowadays, more and more companies offering workplaces for them and this should not surprise us, because after all they only have an extra chromosome (Figure 4).

Figure 4. Keep calm it’s only and extra chromosome (Source: Pinterest)