Hormonal Sensitivity in Patients With Noonan and LEOPARD Syndromes

NCT02486731 | Completed DMC

• 2 other identifiers: C13-592013-A01428-37
• Study Type: observational
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Noonan Syndrome; LEOPARD Syndrome

Keywords

Hormonal sensitivity; bone growth

Outcome Measures

Primary Outcomes (1)

• Phosphorylation of Erk and Akt in fibroblasts

  To evaluate different signaling pathways activation (Ras/MAPK, PI3K/Akt) in response to growth factors/hormones (growth hormone, insulin) in fibroblasts from patients with NS or LS compared to healthy controls

  Baseline

Secondary Outcomes (1)

• Phosphorylation of Erk and Akt in adipocytes

  Baseline

Study Arms (3)

Noonan syndrome

Patients with Noonan syndrome

LEOPARD syndrome

Patients with LEOPARD syndromes

Controls

Healthy subjects

Eligibility Criteria

• Age: 5 Years - 15 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Data collected in patients with Noonan or LEOPARD syndromes will be compared to data of healthy subjects.

You may qualify if:

• 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

You may not qualify if:

• age below 5 or above 15 years
• pregnancy
• In healthy controls: syndromic or chronic disease

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (1)

CIC de Toulouse- Unité pediatrique

Toulouse, 31059, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Fibroblasts, adipocytes, serum

MeSH Terms

Conditions

Noonan Syndrome; LEOPARD Syndrome

Condition Hierarchy (Ancestors)

Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Pulmonary Valve Stenosis; Heart Valve Diseases; Abnormalities, Multiple; Lentigo; Melanosis; Hyperpigmentation; Pigmentation Disorders; Skin Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2014
• First Posted: July 1, 2015
• Study Start: December 16, 2015
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: August 26, 2021

Record last verified: 2021-08

Locations

FR (1)