Hormonal Sensitivity in Patients With Noonan and LEOPARD Syndromes

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.

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Key information

Conditions

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

Age range

5 year–15 year

Sex eligibility

All sexes

Study type

Observational

Primary location

CIC de Toulouse- Unité pediatrique

Toulouse, 31059, France

About this study

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

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

Phosphorylation of Erk and Akt in fibroblasts

Time frame: Baseline

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

Secondary outcomes

Phosphorylation of Erk and Akt in adipocytes

Time frame: Baseline

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

Sponsors and collaborators

Lead sponsor

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

Other Gov

Registry information

Official study title

Consequences of Noonan Syndrome/LEOPARD Syndrome Associated Shp2 Mutations on Different Signaling Pathways Activation: Relationship With Hormonal Sensitivity

Acronym: NOLEO

Important dates

Study start: 2015
Primary completion: 2018
Study completion: 2018
First posted: Jul 1, 2015
Registry last updated: Aug 26, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

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