Ignite Creation Date:
2026-03-26 @ 3:16 PM
Ignite Modification Date:
2026-03-30 @ 12:29 AM
Study NCT ID:
NCT07360704
Status:
COMPLETED
Last Update Posted:
2026-01-22
First Post:
2026-01-13
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Genotypes and Craniofacial Phenotypes in Orthodontic Patients With Marfan and Loeys-Dietz Syndromes
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D008382', 'term': 'Marfan Syndrome'}, {'id': 'D055947', 'term': 'Loeys-Dietz Syndrome'}], 'ancestors': [{'id': 'D001848', 'term': 'Bone Diseases, Developmental'}, {'id': 'D001847', 'term': 'Bone Diseases'}, {'id': 'D009140', 'term': 'Musculoskeletal Diseases'}, {'id': 'D006330', 'term': 'Heart Defects, Congenital'}, {'id': 'D018376', 'term': 'Cardiovascular Abnormalities'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D000015', 'term': 'Abnormalities, Multiple'}, {'id': 'D000013', 'term': 'Congenital Abnormalities'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D003240', 'term': 'Connective Tissue Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}, {'id': 'D019465', 'term': 'Craniofacial Abnormalities'}, {'id': 'D009139', 'term': 'Musculoskeletal Abnormalities'}, {'id': 'D001014', 'term': 'Aortic Aneurysm'}, {'id': 'D000783', 'term': 'Aneurysm'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D001018', 'term': 'Aortic Diseases'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'RETROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 39}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2012-07-07', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-01', 'completionDateStruct': {'date': '2021-07-05', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2026-01-13', 'studyFirstSubmitDate': '2026-01-13', 'studyFirstSubmitQcDate': '2026-01-13', 'lastUpdatePostDateStruct': {'date': '2026-01-22', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-01-22', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-07-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'ANB angle', 'timeFrame': 'Baseline', 'description': '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.'}], 'secondaryOutcomes': [{'measure': 'SNA angle', 'timeFrame': 'Baseline', 'description': 'SNA angle will be measured to assess maxillary position relative to the cranial base.'}, {'measure': 'SNB angle', 'timeFrame': 'Baseline', 'description': 'SNB angle will be measured to assess mandibular position relative to the cranial base.'}, {'measure': 'Vertical skeletal pattern (SN-MP angle)', 'timeFrame': 'Baseline', 'description': 'SN-MP angle will be measured to evaluate mandibular plane inclination and vertical skeletal pattern.'}, {'measure': 'Intermaxillary vertical relationship (PP-MP angle)', 'timeFrame': 'Baseline', 'description': 'PP-MP angle will be measured to assess vertical discrepancy between the palatal plane and the mandibular plane.'}, {'measure': 'Occlusal plane relationships (Occ-MP and Occ-PP angles)', 'timeFrame': 'Baseline', 'description': 'Occ-MP and Occ-PP angles will be measured to assess occlusal plane inclination relative to the mandibular and palatal planes.'}, {'measure': 'Cranial base morphology (N-S-Ar and S-Ar-Go angles)', 'timeFrame': 'Baseline', 'description': 'N-S-Ar and S-Ar-Go angles will be measured to evaluate cranial base flexure and posterior cranial base-mandibular ramus relationship.'}, {'measure': 'Mandibular morphology (Ar-Go-N angle)', 'timeFrame': 'Baseline', 'description': 'Ar-Go-N angle will be measured to assess mandibular morphology and angular configuration.'}, {'measure': 'Facial vertical pattern (N-Go-Gn angle)', 'timeFrame': 'Baseline', 'description': 'N-Go-Gn angle will be measured to assess facial vertical growth pattern.'}, {'measure': 'Maxillary incisor inclination (11-Occ and 11-PP)', 'timeFrame': 'Baseline', 'description': '11-Occ and 11-PP measurements will be used to assess maxillary central incisor inclination relative to the occlusal and palatal planes.'}, {'measure': 'Mandibular incisor inclination (41-Occ and 41-MP)', 'timeFrame': 'Baseline', 'description': '41-Occ and 41-MP measurements will be used to assess mandibular central incisor inclination relative to the occlusal and mandibular planes.'}, {'measure': 'Nasolabial angle (NLA)', 'timeFrame': 'Baseline', 'description': 'The nasolabial angle will be measured to assess soft tissue profile characteristics.'}, {'measure': 'Facial angle (FA)', 'timeFrame': 'Baseline', 'description': 'The facial angle will be measured to evaluate overall facial profile morphology.'}]}, 'oversightModule': {'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Marfan Syndrome', 'Loeys-Dietz Syndrome']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': "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.\n\nA total of 39 patients were enrolled and divided into four groups according to the underlying pathogenic genetic variant:\n\n* Group FBN1Cys: Marfan patients with missense cysteine variants of the FBN1 gene.\n* Group FBN1m: Marfan patients with missense non-cysteine variants of the FBN1 gene.\n* Group FBN1tp: Marfan patients with truncating FBN1 variants (nonsense, frameshift or splicing mutations).\n* Group LD: Patients with Loeys-Dietz syndrome carrying pathogenic variants in TGFBR1 or TGFBR2 genes.\n\nAn 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.\n\nCephalometric 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.\n\nSample 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.\n\nStatistical analysis was conducted using R software, with significance for all tests predetermined at p \\< 0.05."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '18 Years', 'minimumAge': '4 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Patients referring for orthodontic consultation from the Unit Centre for Inherited Cardiovascular Diseases, IRCCS Foundation, University Hospital Policlinico San Matteo, Pavia, Italy', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Diagnosis of Marfan/Loeys-Dietz syndrome;\n* formal request of parents or legal guardians for orthodontic evaluation;\n* aged between 4 and 18;\n* no previous orthopaedic or orthodontic treatment.\n\nExclusion Criteria:\n\n* History of craniofacial anomalies (e.g., cleft lip/palate, craniosynostosis) or syndromic conditions other than Marfan/Loeys-Dietz syndrome;\n* previous orthopaedic or orthodontic treatment;\n* poor quality cephalograms.'}, 'identificationModule': {'nctId': 'NCT07360704', 'briefTitle': 'Genotypes and Craniofacial Phenotypes in Orthodontic Patients With Marfan and Loeys-Dietz Syndromes', 'organization': {'class': 'OTHER', 'fullName': 'University of Pavia'}, 'officialTitle': 'Genotypes and Craniofacial Phenotypes in Orthodontic Patients With Marfan and Loeys-Dietz Syndromes: Observational Retrospective Study', 'orgStudyIdInfo': {'id': '2026-MARFANLDS'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'FBN1Cys (Marfan syndrome, cysteine missense variants)', 'description': 'This arm included patients diagnosed with Marfan syndrome carrying missense variants affecting cysteine residues of the FBN1 gene.', 'interventionNames': ['Diagnostic Test: Cephalometric analysis']}, {'label': 'FBN1m (Marfan syndrome, non-cysteine missense variants)', 'description': 'This arm comprised patients with Marfan syndrome carrying missense FBN1 variants not involving cysteine residues.', 'interventionNames': ['Diagnostic Test: Cephalometric analysis']}, {'label': 'FBN1tp (Marfan syndrome, truncating variants)', 'description': 'Patients in this arm were affected by Marfan syndrome and carried truncating FBN1 variants, including nonsense, frameshift, or splicing mutations.', 'interventionNames': ['Diagnostic Test: Cephalometric analysis']}, {'label': 'LD (Loeys-Dietz syndrome)', 'description': 'This arm included patients diagnosed with Loeys-Dietz syndrome carrying pathogenic variants in TGFBR1 or TGFBR2 genes.', 'interventionNames': ['Diagnostic Test: Cephalometric analysis']}, {'label': 'Control group', 'description': 'A control group matched for age and sex was added for all syndromic patients.', 'interventionNames': ['Diagnostic Test: Cephalometric analysis']}], 'interventions': [{'name': 'Cephalometric analysis', 'type': 'DIAGNOSTIC_TEST', 'description': 'Lateral cephalometric radiographs with cephalometric tracings were performed to evaluate craniofacial patterns.', 'armGroupLabels': ['Control group', 'FBN1Cys (Marfan syndrome, cysteine missense variants)', 'FBN1m (Marfan syndrome, non-cysteine missense variants)', 'FBN1tp (Marfan syndrome, truncating variants)', 'LD (Loeys-Dietz syndrome)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '27100', 'city': 'Pavia', 'state': 'Lombardy', 'country': 'Italy', 'facility': 'Unit of Orthodontics and Pediatric Dentistry - Section of Dentistry - Department of Clinical, Surgical, Diagnostic and Pediatrics - University of Pavia', 'geoPoint': {'lat': 45.19205, 'lon': 9.15917}}], 'overallOfficials': [{'name': 'Andrea Scribante, DDS, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Associate Professor, Principal Investigator'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'Data will be available upon motivated request to the Principal Investigator.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Andrea Scribante', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Associate Professor, Principal Investigator', 'investigatorFullName': 'Andrea Scribante', 'investigatorAffiliation': 'University of Pavia'}}}}