Hormonal Sensitivity in Patients With Noonan and LEOPARD Syndromes

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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT02486731

Acronym

NOLEO

Enrollment

Registered

2015-07-01

Start date

2015-12-16

Completion date

2018-12-31

Last updated

2021-08-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

LEOPARD Syndrome, Noonan Syndrome

Keywords

Hormonal sensitivity, bone growth

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

Interventions

None listed

Study design

Observational model

CASE_CONTROL

Time perspective

CROSS_SECTIONAL

Eligibility

Sex/Gender

ALL

Age

5 Years to 15 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Phosphorylation of Erk and Akt in fibroblasts	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

Measure	Time frame	Description
Phosphorylation of Erk and Akt in adipocytes	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

Countries

France

Outcome results