Genotypes and Craniofacial Phenotypes in Orthodontic Patients With Marfan and Loeys-Dietz Syndromes

NCT07360704 | Completed

• 1 other identifier: 2026-MARFANLDS
• Study Type: observational
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this retrospective observational study is to investigate the association between genotype and craniofacial phenotype in orthodontic patients affected by Marfan and Loeys-Dietz syndromes. A total of 39 patients aged between 4 and 18 years were enrolled and stratified into four groups according to the underlying pathogenic genetic variants. Lateral cephalometric radiographs were analyzed to assess sagittal, vertical, and cranial base skeletal relationships. Each patient group was compared with age- and sex-matched controls, as well as between syndromes and among Marfan subgroups. Statistical analyses were performed to evaluate differences in craniofacial parameters and to explore potential genotype-phenotype correlations relevant for orthodontic diagnosis.

Conditions

Marfan Syndrome; Loeys-Dietz Syndrome

Outcome Measures

Primary Outcomes (1)

• ANB angle

  The ANB angle will be measured on lateral cephalometric radiographs to assess the sagittal skeletal relationship between the maxilla and mandible. Comparisons will be performed between genotype-based case groups and age- and sex-matched controls, as well as among case groups when applicable.

  Baseline

Secondary Outcomes (12)

• SNA angle

  Baseline

• SNB angle

  Baseline

• Vertical skeletal pattern (SN-MP angle)

  Baseline

• Intermaxillary vertical relationship (PP-MP angle)

  Baseline

• Occlusal plane relationships (Occ-MP and Occ-PP angles)

  Baseline

Study Arms (5)

FBN1Cys (Marfan syndrome, cysteine missense variants)

This arm included patients diagnosed with Marfan syndrome carrying missense variants affecting cysteine residues of the FBN1 gene.

Diagnostic Test: Cephalometric analysis

FBN1m (Marfan syndrome, non-cysteine missense variants)

This arm comprised patients with Marfan syndrome carrying missense FBN1 variants not involving cysteine residues.

Diagnostic Test: Cephalometric analysis

FBN1tp (Marfan syndrome, truncating variants)

Patients in this arm were affected by Marfan syndrome and carried truncating FBN1 variants, including nonsense, frameshift, or splicing mutations.

Diagnostic Test: Cephalometric analysis

LD (Loeys-Dietz syndrome)

This arm included patients diagnosed with Loeys-Dietz syndrome carrying pathogenic variants in TGFBR1 or TGFBR2 genes.

Diagnostic Test: Cephalometric analysis

Control group

A control group matched for age and sex was added for all syndromic patients.

Diagnostic Test: Cephalometric analysis

Interventions

Cephalometric analysis DIAGNOSTIC_TEST

Lateral cephalometric radiographs with cephalometric tracings were performed to evaluate craniofacial patterns.

Control group; FBN1Cys (Marfan syndrome, cysteine missense variants); FBN1m (Marfan syndrome, non-cysteine missense variants); FBN1tp (Marfan syndrome, truncating variants); LD (Loeys-Dietz syndrome)

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients referring for orthodontic consultation from the Unit Centre for Inherited Cardiovascular Diseases, IRCCS Foundation, University Hospital Policlinico San Matteo, Pavia, Italy

You may qualify if:

• Diagnosis of Marfan/Loeys-Dietz syndrome;
• formal request of parents or legal guardians for orthodontic evaluation;
• aged between 4 and 18;
• no previous orthopaedic or orthodontic treatment.

You may not qualify if:

• History of craniofacial anomalies (e.g., cleft lip/palate, craniosynostosis) or syndromic conditions other than Marfan/Loeys-Dietz syndrome;
• previous orthopaedic or orthodontic treatment;
• poor quality cephalograms.

Sponsors & Collaborators

• Andrea Scribante: lead

Study Sites (1)

Unit of Orthodontics and Pediatric Dentistry - Section of Dentistry - Department of Clinical, Surgical, Diagnostic and Pediatrics - University of Pavia

Pavia, Lombardy, 27100, Italy

Location

MeSH Terms

Conditions

Marfan Syndrome; Loeys-Dietz Syndrome

Condition Hierarchy (Ancestors)

Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Aortic Aneurysm; Aneurysm; Vascular Diseases; Aortic Diseases

Study Officials

• Andrea Scribante, DDS, PhD

  Associate Professor, Principal Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor, Principal Investigator

Study Record Dates

• First Submitted: January 13, 2026
• First Posted: January 22, 2026
• Study Start: July 7, 2012
• Primary Completion: July 1, 2021
• Study Completion: July 5, 2021
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)