ERN-SKIN TRAINING SESSION IN GHENT (Belgium)

16th December : ERN-Skin, training session in Ghent (Belgium).

Organised by Pr Bert Callewaert, this session included a whole chapter dedicated to Cutis Laxa and all the scientific progress about it. See below  “What’s new about Cutis Laxa».

Other pathologies were also presented and patients representatives took part in a panel discussion « Patients’ burden : What healthcare professionals need to know ? ».

What’s new about Cutis Laxa

 

During the training session in Ghent, the first part of the morning was almost totally dedicated to Cutis Laxa.

Several cases were presented by young doctors.

 

An overview talk on Cutis Laxa presented the clinical classification of Cutis Laxa disorders. Cutis laxa has an extensive clinical and molecular heterogeneity.

 

Based on a flowchart addressing the presence or absence of the main clinical symptoms, over 90 % of the people suffering from Cutis Laxa are correctly classified.

The main symptoms are: arterial tortuosity, emphysema, wrinkled/lax skin, neurological issues with or without intrauterine growth retardation (IUGR). In addition to those main symptoms, minor criteria are suggested for each type: arachnodactyly, aortic aneurysm, aortic stenosis, respiratory distress, diverticula, hearing loss, large anterior fontanelle, joint contractures, hip dislocation or ataxia.

The classification was based on a ‘learning’ cohort of patients known to the Ghent University Hospital. Refinement of the classification is ongoing based on a confirmation cohort from literature (650 patients).  Patients are classified based upon clinical examination and the main symptoms into major groups. Further refinement based on the minor criteria will eventually be able to predict the causal gen in over 95% of patients.

As an example, a patient with a lax skin, neurologic issues, intrauterine growth retardation as well as hip dislocation and ataxia, associated with ALDH18A1 mutation, will be diagnosed with Autosomal Recessive Cutis Laxa Type 3 or Syndrome De Barsy (ARCL3).

This new classification will help to a quicker diagnosis, interpretation of next-generation sequencing data and provide an opportunity of specific management and care for each type of Cutis Laxa.

Ghent University welcomed this session in its historic buildings.

Pure marvel, as is all the city of Ghent..….

 

ARTERYLASTIC : First real therapeutic hope

ARTERYLASTIC : First real therapeutic hope for vascular issue in Dominant Cutis Laxa.

 

ARTERYLASTIC derives from researches lead in Lyon (France) by Dr Romain Debret. Originating from the idea that if one can make prosthetics for a joint, maybe we could make prosthestics for a failing elastin, this project is funded by the French National Agency for Research. Selected in 2018, it will start in January 2019.

The project involves 3 laboratories from the Rhône-Alpes area: Laboratory for Tissue Biology and Therapeutic Engineering (National Center for Scientific Research, Lyon), Laboratory for Hypoxia and Cardiovascular and Respiratory Physiopathologies (National Institute of Health and Medical Research, Grenoble), and Sainbiose Laboratory (National Institute of Health and Medical Research, Saint-Etienne).

The main aim of the project is to develop a synthetic elastic protein as medicine agent to improve or restore the vascular elasticity when it is failing in genetic disorders such as Cutis Laxa and Williams Syndrome, but also in non syndromic pathologies such as sleeping apneia.

This project aims to analyse the way the synthetic protein is acting and evaluate its efficiency in pertinent biological models.

The « DHERMIC » project, which preceded ARTERYLASTIC, already provided a wide set of solid data regarding the skin for the synthetic elastic protein. Recent preliminary results regarding the integration in blood vessels walls in fishes and mice are very promising.

An important part of the work will also be dedicated to the pharmacological formulation and certification to allow for the implementation of Clinical Trials at the end of the project (late 2021).

A New Type of Cutis Laxa

In March, the American Journal of Medecine Genetics published an article showing that a mutation on the gene PTDSS1 leads to a very rare type of Cutis Laxa :  Lenz-Majewski Syndrome (LMS) . It includes Cutis Laxa with growth delay, dwarfism and intellectual delay. According to this study of 3 cases, this is a new type of Cutis Laxa that needs to be added to those already identified.

12 different mutations have been identified

As of today, 12 different mutations have been identified leading to Cutis Laxa. That is why Cutis Laxa classification will soon be reviewed.

  • Elastine (ELN) (2 mutations) – ADCL
  • Fibuline5 (FBLN5) – ARCL1A
  • Fibuline4 (FBLN4) – ARCL1B
  • LTBP4 – ARCL1C
  • ATP6V0A2 – ARCL2A
  • PYCR1 – ARCL2B
  • ATP6V1E1 / ATP6V1A – ARCL2C
  • ALDH18A1 – ARCL3 (De Barsy Syndrom)
  • SCYL1BP1 (Géroderma Osteodysplastica)
  • ATP7A (Occipital Horn Syndrom)
  • RIN2 (MACS Syndrom)

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