Marfan SyndromeNCT07360704
Genotypes and Craniofacial Phenotypes in Orthodontic Patients With Marfan and Loeys-Dietz Syndromes
An observational study of Marfan Syndrome and Loeys-Dietz Syndrome, run by Andrea Scribante at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 to 18 years
- Conditions the study is for
- Marfan Syndrome, Loeys-Dietz Syndrome
- What is being tested?
- Cephalometric analysis
- How many people
- 39 participants
- Where
- 1 siteItaly
- Study dates
- 7 Jul 2012to 5 Jul 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Patients referring for orthodontic consultation from the Unit Centre for Inherited Cardiovascular Diseases, IRCCS Foundation, University Hospital Policlinico San Matteo, Pavia, Italy
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Unit of Orthodontics and Pediatric Dentistry - Section of Dentistry - Department of Clinical, Surgical, Diagnostic and Pediatrics - University of Pavia
Pavia, Lombardy, 27100
About this study
Official title: Genotypes and Craniofacial Phenotypes in Orthodontic Patients With Marfan and Loeys-Dietz Syndromes: Observational Retrospective Study
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.
Read the detailed description
This retrospective observational study aims to investigate the association between genotype and craniofacial phenotypic variation in orthodontic patients affected by Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). Patients aged between 4 and 18 years who referred to the Unit of Orthodontics and Paediatric Dentistry and had a confirmed genetic diagnosis were considered eligible for inclusion. Parents or legal guardians provided informed consent prior to data collection.
A total of 39 patients were enrolled and divided into four groups according to the underlying pathogenic genetic variant:
- Group FBN1Cys: Marfan patients with missense cysteine variants of the FBN1 gene.
- Group FBN1m: Marfan patients with missense non-cysteine variants of the FBN1 gene.
- Group FBN1tp: Marfan patients with truncating FBN1 variants (nonsense, frameshift or splicing mutations).
- Group LD: Patients with Loeys-Dietz syndrome carrying pathogenic variants in TGFBR1 or TGFBR2 genes.
An age- and sex-matched control group without genetic disorders and without previous orthodontic treatment was selected for each study group. All patients underwent orthodontic diagnostic records including lateral cephalometric radiographs. Due to the retrospective nature of the study and the use of different radiographic units, only angular cephalometric measurements were considered.
Cephalometric analysis was performed using dedicated software according to Giannì's method, evaluating sagittal, vertical and cranial base relationships. Each patient was compared with the corresponding control group, between MFS and LDS patients, and among the Marfan subgroups. All measurements were performed by a single operator and intra-rater reliability was assessed.
Sample size was defined by the availability of patients affected by these rare genetic disorders who met the inclusion criteria during the study period. Descriptive statistics were calculated for all cephalometric parameters. Shapiro-Wilk test was applied to assess data normality. Differences between groups were evaluated using ANOVA, followed by Tukey's post-hoc test when appropriate.
Statistical analysis was conducted using R software, with significance for all tests predetermined at p < 0.05.
- Conditions
- Marfan Syndrome, Loeys-Dietz Syndrome
- Being tested
- Cephalometric analysis
- Medical subject headings
- Marfan Syndrome, Loeys-Dietz Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cephalometric analysisDiagnostic test
Lateral cephalometric radiographs with cephalometric tracings were performed to evaluate craniofacial patterns.
| Study group | Role | What they receive |
|---|---|---|
| FBN1Cys (Marfan syndrome, cysteine missense variants) | This arm included patients diagnosed with Marfan syndrome carrying missense variants affecting cysteine residues of the FBN1 gene. Receives: 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. Receives: 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. Receives: 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. Receives: Diagnostic Test: Cephalometric analysis | |
| Control group | A control group matched for age and sex was added for all syndromic patients. Receives: Diagnostic Test: Cephalometric analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline
Secondary outcomes (12)
SNA angle
SNA angle will be measured to assess maxillary position relative to the cranial base.
Measured: Baseline
SNB angle
SNB angle will be measured to assess mandibular position relative to the cranial base.
Measured: Baseline
Vertical skeletal pattern (SN-MP angle)
SN-MP angle will be measured to evaluate mandibular plane inclination and vertical skeletal pattern.
Measured: Baseline
Intermaxillary vertical relationship (PP-MP angle)
PP-MP angle will be measured to assess vertical discrepancy between the palatal plane and the mandibular plane.
Measured: Baseline
Occlusal plane relationships (Occ-MP and Occ-PP angles)
Occ-MP and Occ-PP angles will be measured to assess occlusal plane inclination relative to the mandibular and palatal planes.
Measured: Baseline
Cranial base morphology (N-S-Ar and S-Ar-Go angles)
N-S-Ar and S-Ar-Go angles will be measured to evaluate cranial base flexure and posterior cranial base-mandibular ramus relationship.
Measured: Baseline
Mandibular morphology (Ar-Go-N angle)
Ar-Go-N angle will be measured to assess mandibular morphology and angular configuration.
Measured: Baseline
Facial vertical pattern (N-Go-Gn angle)
N-Go-Gn angle will be measured to assess facial vertical growth pattern.
Measured: Baseline
Maxillary incisor inclination (11-Occ and 11-PP)
11-Occ and 11-PP measurements will be used to assess maxillary central incisor inclination relative to the occlusal and palatal planes.
Measured: Baseline
Mandibular incisor inclination (41-Occ and 41-MP)
41-Occ and 41-MP measurements will be used to assess mandibular central incisor inclination relative to the occlusal and mandibular planes.
Measured: Baseline
Nasolabial angle (NLA)
The nasolabial angle will be measured to assess soft tissue profile characteristics.
Measured: Baseline
Facial angle (FA)
The facial angle will be measured to evaluate overall facial profile morphology.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2026
- Study start7 Jul 2012
- Primary completion1 Jul 2021
- Study completion5 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Marfan SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Andrea Scribante
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Andrea Scribante, University of Pavia
- Investigators
- Andrea Scribante, DDS, PhD, Principal investigator, Associate Professor, Principal Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07360704
- Sponsor's protocol ID
- 2026-MARFANLDS
- Status last verified
- Jan 2026
- First submitted
- 13 Jan 2026
- Last updated
- 22 Jan 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data will be available upon motivated request to the Principal Investigator.
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genotypes and Craniofacial Phenotypes in Orthodontic Patients With Marfan and Loeys-Dietz Syndromes: Observational Retrospective Study
- ClinicalTrials.gov ID
- NCT07360704
- Acronym / sponsor ID
- 2026-MARFANLDS
- Conditions
- Marfan Syndrome, Loeys-Dietz Syndrome
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Andrea ScribanteUniversity, hospital or other
- Study start
- 7 Jul 2012 (actual)
- Primary completion
- 1 Jul 2021 (actual)
- Study completion
- 5 Jul 2021 (actual)
- First posted
- 22 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This retrospective observational study aims to investigate the association between genotype and craniofacial phenotypic variation in orthodontic patients affected by Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). Patients aged between 4 and 18 years who referred to the Unit of Orthodontics and Paediatric Dentistry and had a confirmed genetic diagnosis were considered eligible for inclusion. Parents or legal guardians provided informed consent prior to data collection.
A total of 39 patients were enrolled and divided into four groups according to the underlying pathogenic genetic variant:
- Group FBN1Cys: Marfan patients with missense cysteine variants of the FBN1 gene.
- Group FBN1m: Marfan patients with missense non-cysteine variants of the FBN1 gene.
- Group FBN1tp: Marfan patients with truncating FBN1 variants (nonsense, frameshift or splicing mutations).
- Group LD: Patients with Loeys-Dietz syndrome carrying pathogenic variants in TGFBR1 or TGFBR2 genes.
An age- and sex-matched control group without genetic disorders and without previous orthodontic treatment was selected for each study group. All patients underwent orthodontic diagnostic records including lateral cephalometric radiographs. Due to the retrospective nature of the study and the use of different radiographic units, only angular cephalometric measurements were considered.
Cephalometric analysis was performed using dedicated software according to Giannì's method, evaluating sagittal, vertical and cranial base relationships. Each patient was compared with the corresponding control group, between MFS and LDS patients, and among the Marfan subgroups. All measurements were performed by a single operator and intra-rater reliability was assessed.
Sample size was defined by the availability of patients affected by these rare genetic disorders who met the inclusion criteria during the study period. Descriptive statistics were calculated for all cephalometric parameters. Shapiro-Wilk test was applied to assess data normality. Differences between groups were evaluated using ANOVA, followed by Tukey's post-hoc test when appropriate.
Statistical analysis was conducted using R software, with significance for all tests predetermined at p < 0.05.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| FBN1Cys (Marfan syndrome, cysteine missense variants) | – | Diagnostic Test: Cephalometric analysisThis arm included patients diagnosed with Marfan syndrome carrying missense variants affecting cysteine residues of the FBN1 gene. |
| FBN1m (Marfan syndrome, non-cysteine missense variants) | – | Diagnostic Test: Cephalometric analysisThis arm comprised patients with Marfan syndrome carrying missense FBN1 variants not involving cysteine residues. |
| FBN1tp (Marfan syndrome, truncating variants) | – | Diagnostic Test: Cephalometric analysisPatients in this arm were affected by Marfan syndrome and carried truncating FBN1 variants, including nonsense, frameshift, or splicing mutations. |
| LD (Loeys-Dietz syndrome) | – | Diagnostic Test: Cephalometric analysisThis arm included patients diagnosed with Loeys-Dietz syndrome carrying pathogenic variants in TGFBR1 or TGFBR2 genes. |
| Control group | – | Diagnostic Test: Cephalometric analysisA control group matched for age and sex was added for all syndromic patients. |
Who may qualify
- Ages
- 4 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Patients referring for orthodontic consultation from the Unit Centre for Inherited Cardiovascular Diseases, IRCCS Foundation, University Hospital Policlinico San Matteo, Pavia, Italy
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cephalometric analysisLateral cephalometric radiographs with cephalometric tracings were performed to evaluate craniofacial patterns. | Diagnostic test | Control group, FBN1Cys (Marfan syndrome, cysteine missense variants), FBN1m (Marfan syndrome, non-cysteine missense variants), FBN1tp (Marfan syndrome, truncating variants), LD (Loeys-Dietz syndrome) |
Primary outcome
ANB angle
Time frame: Baseline
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.
12 secondary outcomes
SNA angle
Time frame: Baseline
SNB angle
Time frame: Baseline
Vertical skeletal pattern (SN-MP angle)
Time frame: Baseline
Intermaxillary vertical relationship (PP-MP angle)
Time frame: Baseline
Occlusal plane relationships (Occ-MP and Occ-PP angles)
Time frame: Baseline
Cranial base morphology (N-S-Ar and S-Ar-Go angles)
Time frame: Baseline
Mandibular morphology (Ar-Go-N angle)
Time frame: Baseline
Facial vertical pattern (N-Go-Gn angle)
Time frame: Baseline
Maxillary incisor inclination (11-Occ and 11-PP)
Time frame: Baseline
Mandibular incisor inclination (41-Occ and 41-MP)
Time frame: Baseline
Nasolabial angle (NLA)
Time frame: Baseline
Facial angle (FA)
Time frame: Baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2026.
- Individual participant dataSharing planned: No. Data will be available upon motivated request to the Principal Investigator.
Related trials for Marfan Syndrome
RecruitingObservational study
Asprosin and miRNA Expression in Young Women With Metabolic Syndrome
Metabolic Syndrome, Insulin Resistance
Enrolling by invitationObservational study
Advanced Ultrasound Signal Processing of Suspicious Breast Images
Breast Cancer, Breast Cyst
RecruitingObservational study
Pregnancy in Women With Rare Multisystemic Vascular Diseases: COGRare5 Study
Vascular Anomaly, Osler Rendu Disease
Not yet recruitingObservational study
Asprosin in Behect Patients
Behcet Disease
Not yet recruitingObservational study
Serum Asprosin, Metabolic Syndrome, and Cardiometabolic Risk in Rheumatoid Arthritis
Rheumatoid Arthritis, Metabolic Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrea Scribante, DDS, PhD principal investigator
Associate Professor, Principal Investigator
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Marfan Syndrome and Loeys-Dietz Syndrome, run by Andrea Scribante at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ANB angle (time frame: Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2026.