Hormonal Sensitivity in Patients With Noonan and LEOPARD Syndromes

NCT ID: NCT02486731

Last Updated: 2021-08-26

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 27 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-12-16
• Study Completion Date: 2018-12-31

Brief Summary

Noonan and LEOPARD syndromes share, with variable severity, different clinical traits, notably craniofacial manifestations, cardiopathies, short stature, and juvenile cancers.

The main genetic cause of these syndromes is missense mutation of the gene encoding the ubiquitous tyrosine phosphatase Shp2, found in more than half the patients with NS and in 80% of LS cases. Shp2 plays pivotal roles in development, growth, and metabolism by regulating key signalling pathways (Ras/Mitogen activated protein kinase (MAPK), Phosphoinositide-3 Kinases (PI3K)/Akt) in response to growth factors/hormones. Deregulation of these signalling pathways has been causally linked to NS and LS pathophysiology.

This project aims at better understanding hormonal sensitivity abnormalities in patients with Noonan syndrome (NS) or LEOPARD syndrome (LS) caused by mutations of the tyrosine phosphatase Shp2.

To reach this goal, the investigators will take advantage of different tissues (fibroblasts ± adipocytes) from patients with NS / LS compared to healthy controls.

All patients will have a skin biopsy and only patients about to undergo surgery will have a adipose tissue biopsy.

Detailed Description

The activation of different signaling pathways (Ras/MAPK, PI3K/Akt) in response to growth factors/hormones (growth hormone, insulin) in fibroblasts and/or in adipocytes from patients with NS or LS will be compared to those of healthy subjects.

These data will be correlated to clinical, hormonal, and biochemical characteristics of patients

Conditions

Noonan Syndrome; LEOPARD Syndrome

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Noonan syndrome

Patients with Noonan syndrome

No interventions assigned to this group

LEOPARD syndrome

Patients with LEOPARD syndromes

No interventions assigned to this group

Controls

Healthy subjects

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

Patients with Noonan syndrome (NS) or LEOPARD syndrome (LS):

• female or male
• age between 5 to 15 years
• clinical diagnosis of NS or LS according to published criteria
• signed informed consent of parents

Healthy controls:

• female or male
• age between 5 to 15 years
• no personal history of syndrome or chronic disease
• planned surgical procedure
• signed informed consent of parents

Exclusion Criteria

• age below 5 or above 15 years
• pregnancy

In healthy controls: syndromic or chronic disease

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CIC de Toulouse- Unité pediatrique

Toulouse, , France

Countries

France

Other Identifiers

2013-A01428-37

Identifier Type: REGISTRY

Identifier Source: secondary_id

C13-59

Identifier Type: -

Identifier Source: org_study_id