General description of Koolen De Vries Syndrome

Koolen De Vries syndrome, the scientific name of which is Microdélétion 17q21.31, is a rare genetic disorder .

Genetic disease means disease caused by an abnormality in the behavior of a gene.

Rare means that the number of people affected is limited compared to the general population.

Microdeletion 17q21.31 is therefore a genetic state in which a tiny fragment is missing from one of the 46 chromosomes, there is a lack of a small amount of genetic material.

A small number of people with Koolen De Vries syndrome do not have a chromosome 17 microdeletion but a mutation in the KANSL1 * gene which results in a copy of the gene that does not work.

* Translation of the definition of the KANSL 1 gene from the https://ghr.nlm.nih.gov/gene/KANSL1 site: The KANSL1 gene provides instructions for creating an element (subunit) of a group of interacting proteins called the NSL regulatory complex KAT8. This complex is classified as a histone acetyltransferase (HAT) complex. It helps regulate gene activity (expression) by modifying chromatin, the DNA and protein complex that conditions DNA in chromosomes.
The protein produced from the KANSL1 gene is found in most organs and tissues in the body before birth and throughout life. Due to its involvement in controlling the activity of other genes, this protein plays an important role in the development and functioning of many parts of the body.

* Translation of the definition of the KANSL 1 gene from the site https://ghr.nlm.nih.gov/gene/KANSL1 : The KANSL1 gene provides instructions for the creation of an element (subunit) of a group of interacting proteins called the NSL regulatory complex KAT8. This complex is classified as a histone acetyltransferase (HAT) complex. It helps regulate gene activity (expression) by altering chromatin, the complex of DNA and proteins that conditions DNA in chromosomes. The protein produced from the KANSL1 gene is found in most organs and tissues of the body before birth and throughout life. Due to its involvement in controlling the activity of other genes, this protein plays an important role in the development and function of many parts of the body.

What is a Kool Kid?

 

As the syndrome has only recently been described, most of the people known to be carriers of this syndrome are still children, adolescents or young adults. The oldest known person of Drs Koolen and De Vries is a Spanish person born in the mid-1960s.

In connection with the name of the syndrome (see history below), these children are called Kool Kids in the community of parents of children with the syndrome.

It is also true that the vast majority of people with the syndrome are calm or even dilettante.

The above children and adolescents are carriers of the syndrome from 3 different families, yet don't they look similar?

History of the syndrome

 

If many children are already known to genetic services, we have to wait for technical progress in research and the year 2006 to be able to diagnose the syndrome under the name of the defective gene, 17q21.31 .

Today, anyone who comes into contact with a genetics service can be diagnosed.

We even know of children diagnosed in utero around the world. In France, Koolen de Vries syndrome is now sought after during amiosynthesis.

The Dutch professors Koolen and De Vries were interested in the syndrome very early on, they discovered it and are still continuing their research. Very involved, they go to meet families all over the world and participate in many seminars organized by these same families. (request in progress for photo agreement)

They created a database called Syndrome Monitor and, at the end of 2015, an international database, Genida , was born. This new database is managed in France by Professors Mandel and Colin . It lists all the symptoms related to the syndrome and at all ages. In particular, this allows us to communicate on the progress of our children and the possible risks to alert doctors and families to the checks to be carried out systematically.

At the same time, thanks to the Internet, parents communicate. The first site is English and run by a mother. It quickly brought together a few families from all over the world.

With the success of Facebook and more and more diagnoses, a Facebook page is created. In 2015, a first French page dedicated to families was opened, with the collective choice of only accepting parents or siblings living with a Koolen de Vries child: Koolen de Vries France - microdeletion syndrome17q21.31 . Its access is restricted and is obtained after request to the administrators. To create a dynamic of mutual aid between caregivers, who are also isolated, a Facebook page of the Association Koolen De Vries France le coin des pros was opened in May 2018; it is aimed at parents and the medical community for an exchange of practices.

Today, families are grouped together mainly by country by opening new pages. This makes it possible to inform each other according to each culture and the policies conducted, the aid being able to be very disparate from one country to another.

In 2012, the 17q21.31 syndrome was renamed Koolen De Vries Syndrome . Parents from all over the world are thrilled for two reasons:

  • recognition for these two teachers,

  • a name that corresponds well to our children in view of their character.

We can say that the Kool Kids family was born on this date.

In 2014, the American indie pop group, Echosmith released a song called "Cool Kids". This song quickly became a hymn within the growing community of parents.

In 2018, a few parents braved their geographic remoteness and created the Koolen De Vries France association, of which this website and the Koolen De Vries France - KDVF Facebook page are the showcases.

Most frequent features of the syndrome

(Based on the micro-deletion guide 17q21.31, Unique English association, translation of Valentin APAC association)

 

The Kool kids seem to be more present in Western countries + Australia. No doubt because the techniques are more developed there but certainly also because of our genetic architecture. Indeed, in humans, for an equal amount male / female, there may be a polymorphic inversion called H2. This inversion is present in 25% of the European population and very little present in Asian and African populations. H2 has no known consequences but is systematically present in one of the parents of Kool kid, which may also explain the low number of Kool Kids in populations of Asia or Africa. However, it is not advisable to test the H2 systematically.

No more than 50% of the symptoms related to the syndrome are found in the Kool kids population and there is no difference between the symptoms found in people with the mutation of chromosome 17 or the absence of KANSL 1. The size of the deletion is almost the same in everyone due to its size and is also found in the same place of the gene for everyone. On the other hand, the causes of the deletion are still unknown to this day. It is also still impossible to know why there are so many different symptoms for a single missing gene and with so many Kool kids as there are different associated symptoms; there is no similar Kool kid. Here are the most common symptoms:

Newborns are very hypotonic.

In addition to this, you need to know more about it.

Almost all babies have low muscle tone (hypotonia), their muscle and skin tissue is too "elastic". This has many consequences on the evolution of their motor development:

In addition to this, you need to know more about it.

  • sucking more difficult, slowness for feedings. Some may need a feeding tube. At birth, they may be unable to hold on, and they suck so weakly that they cannot meet their own nutritional needs. Expressed breast milk and an energy-enriched formula can be given through a nasogastric tube inserted through the nose until they are strong and mature enough to feed directly from the breast or bottle. False routes are also noticed in some children. Chewing food is difficult, which requires vigilance depending on the meals served.

Example of Kool kid with laryngomalacia: laryngeal malformation causing a stridor. Lots of noise for not much. The stridor is stronger during suction but also present during deep breaths. It subsided and then disappeared over time.

Example of Kool kid with laryngomalacia: laryngeal malformation causing a stridor. Lots of noise for not much. The stridor is stronger during suction but also present during deep breaths. It subsided and then disappeared over time.

  • tongue often pushed forward or even out. Some people also have a tongue that is too thick and cannot fit in the oral cavity, a symptom called macroglossia. This can sometimes require a surgical operation (two specialists in France for this type of surgery).

In addition to this, you need to know more about it.

  • difficulty speaking and then speaking clearly. Few children produce distinct words before the age of 2 and sometimes it takes until 6 years (very rare adolescents or adults do not speak at all). Communication is done a lot by gestures, facial expressions or vocal noises. Each parent learns to recognize their child's language. A few learn limited sign language. Children have difficulty reproducing all the sounds of language. They have difficulty organizing and making facial movements. This is called verbal dyspraxia (we can also say buccofacial, or oral or orofacial or oro-bucco-facial). This is a marked feature of the syndrome. Along with the strengthening of the tissues, this dyspraxia subsides and language develops.

Discussion between a 7 and a half year old Kool Kid and Santa Claus

  • delayed head support, sitting, standing and gait acquisition. Generally, control of bodily movements (fine and gross motor skills) develops slowly and later than in children without chromosomal abnormalities. Some children walk before 2 years old, others not before 4 or 5 years old. Muscle tone improves with age, but this low tone can persist and have other consequences, such as a deviation of the spine. Early intervention by the physiotherapist, occupational therapy or other approaches such as balneotherapy are important. The exercises to tone up are essential. Some children may need adapted seats, walking aids, specific shoes or a wheelchair for outdoors.

10 months,

I still tumble

18 months,

i don't walk

but can move

23 months,

I'm almost there

but it's faster in youpala

25 months,

That's it !

I walk

4 years and 4 months,

the rope ladder holds no secrets for me

4 years and 8 months,

difficult cycling, even with small wheels. I have little strength in my legs.

5 years and 9 months,

I start in tree climbing

Corset.jpg

Examples of corsets

EEG.jpg

EEG, impressive with all these connections but completely painless.

  • We notice that children evolve differently, nevertheless certain checks are strongly recommended so as not to miss essential care:

In addition to this, you need to know more about it.

- evaluation of general development (for example a doctor in rehabilitation and adaptation, in particular for problems

spine)

- phoniatric check-up (swallowing)

- speech therapy assessment (language)

- audiological assessment

- kidney ultrasound

- heart assessment

- MRI of the brain

- EEG in case of suspicion of epilepsy

- evaluation of a lack of growth hormones in case of short stature

- ophthalmic assessment

- dermatological vigilance (often numerous moles)

  • In terms of education, the courses are also very varied and depend on the level of mental handicap, the majority of children are educated with an AESH during the kindergarten period. Some continue in primary but the majority then integrate specialized courses, ULIS, IME. Many learn to read, a few manage to write with a pencil, but fine motor skills are often a real obstacle. The keyboard is then a nice alternative. Almost everyone has a lack of math skills. It is a difficult concept to integrate. If they can learn lists of operations such as addition tables by heart, they do not know how to use them and do not see their purpose. In immersion, they are able to learn several languages ​​(parents of different origins or expatriation).

In addition to this, you need to know more about it.

In addition to this, you need to know more about it.

  • Behaviorally, our children are generally very sociable, friendly, affectionate, empathetic and cooperative, reckless. Which can also be difficult to deal with growing up as they have a hard time discerning right from wrong and might follow anyone who is a little sympathetic at first. They love to laugh and make a lot of jokes. They are children open to others and not at all withdrawn into themselves.

Laughing, joking eyes

and malicious ....

a big smile...

faces...

13 03 18 (2).jpg

far from creating melancholy.

  • Our children are very similar physically, we are talking about the "kool kids" family. In general, they have a pear-shaped nose, rounded forehead, wide-set eyes, somewhat large ears, thin lips and an elongated face. They often have light hair and eyes. Do not try to represent them to yourself with these scary descriptions, rather go see the photo at the top of the page. You will see that indeed, they look very similar but that they are also very beautiful.

Scientific view of the Radbound University Medical Center

University medical center where Doctors Koolen and de Vries officiate