Pubertal Development in Patients with RASopathies

Retrospective, single-centre, non-profit, observational study on pubertal development in patients with RASopathies.

Literature data shows that puberty can be delayed by about 2 years in patients with RASopathies and this has been associated with a reduced peak growth rate. To date, only a few numerically limited case series without molecular characterisation have been published.

This descriptive study should improve knowledge of pubertal development and its influence on growth and final stature. The primary aims are to describe the age of onset and progression of pubertal development in the cohort of patients with RASopathies, both male and female, and to describe the influence of pubertal development on statural growth and final stature in the same cohort.

Study Overview

• Status: Recruiting
• Conditions: RASopathy

Detailed Description

The study enrolls patients with molecularly confirmed RASopathy and completed pubertal development who referred to the Centre for Rare Congenital-Malformative Diseases of the Pediatrics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy, between 01/01/2001 and 31/12/2023. Being a Regional Centre, it is possible to enrol a significant number of patients.

The primary aims of the study are to describe the age of onset and progression of pubertal development in this cohort of patients, and to describe the influence of pubertal development on statural growth and final stature. The secondary aim is to compare the trends of pubertal development and statural growth at puberty in GH-treated and untreated patients with RASopathies.

The study consists of the retrospective collection and analysis of anthropometric data on growth and pubertal development of the cohort of patients enrolled by consulting their medical records. More in detail, for each patient will be collected demographic data, prenatal data, personal medical history, pubertal history, organ involvement data, outpatient clinical evaluation with height, weight, and growth rate, data on GH therapy, if any, radiological assessments and laboratory tests, and the molecular RASopathy diagnosis by NGS panel and/or Sanger sequencing of target genes.

Due to the observational nature of the study, enrolled patients are treated according to clinical practice.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Federica Tamburrino, MD, PhD; Phone Number: 00390512143723; Email: federica.tamburrino@aosp.bo.it

Study Locations

• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna
    • Contact: Federica Tamburrino, MD, PhD; Phone Number: 00390512143723; Email: federica.tamburrino@aosp.bo.it
    • Contact: Federica Tamburrino, Md, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients referred to the Pediatrics Unit of the IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy, between 01/01/2001 and 31/12/2023 with molecularly confirmed RASopathy and completed pubertal development.

Description

Inclusion Criteria:

• Age at enrollment between 8 and 35 years, extremes included;
• Molecularly confirmed clinical diagnosis of RASopathy;
• Complete pubertal development;
• Obtaining informed consent for participation in the study and processing of personal data.

Exclusion Criteria:

• None.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age of pubertal onset in males and females in all different genotypes	years, months	at baseline
Proportion of males and females with delayed puberty in all different genotypes	percentage %	at baseline
Age at the time of the presence of dosable serum LH (≥0,1 U/L) in males and females in all different genotypes	years, months	at baseline
Age at time of presence of dosable serum estradiol (>15 pg/ml) in females in all different genotypes	years, months	at baseline
Age at time of presence of dosable serum testosterone (>0,2 ng/ml) in males in all different genotypes	years, months	at baseline
Age of reaching Peak Height Velocity in males and females in all different genotypes	years, months	at baseline
Statural gain at puberty in males and females in all different genotypes	cm	at baseline
Peak Height Velocity in males and females in all different genotypes	cm/year	at baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Height at first evaluation, final height, and statural gain at puberty in GH-treated and non-treated patients	cm	at baseline
Peak Height Velocity in GH-treated and non-treated patients	cm/year	at baseline
Age of reaching Peak Height Velocity in GH-treated and non-treated patients	years, months	at baseline

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Investigators: Principal Investigator: Federica Tamburrino, MD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2024
• Primary Completion (Estimated): January 31, 2025
• Study Completion (Estimated): February 28, 2025

Study Registration Dates

• First Submitted: December 3, 2024
• First Submitted That Met QC Criteria: January 13, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 13, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: RASopathy
• Other Study ID Numbers: SN_PUBERTA2023

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No