Oral Health, Dento-facial Condition and OHRQoL in Subjects With Mowat-Wilson Syndrome: an Epidemiologic Study. (ORALMOWAT26)

Mowat-Wilson Syndrome (MWS) is a rare syndrome characterized by the presence of facial gestalt and delayed psychomotor development, variably associated with intellectual disability, epilepsy, Hirschsprung's disease (HSCR) and multiple congenital malformations.

Although there is evidence of the presence of dental and craniofacial anomalies in MWS, little epidemiological data is available to date.

The goal of this observational study is to assess oral health and dento-facial phenotype of people affected by Mowat-Wilson Syndrome (MWS). In addition, the Oral Health Related Quality of Life (OHRQoL) will be investigated.

Study Overview

• Status: Not yet recruiting
• Conditions: Periodontal Diseases; Dental Caries; Tooth Diseases; Malocclusion; Craniofacial Abnormalities; Tooth Abnormalities; Oral Mucosal Disease; Oral Health Related Quality of Life (OHRQoL); Sleep Related Breathing Disorder; Mowat-Wilson Syndrome

Detailed Description

Subjects will be recruited from those attending the annual meeting of Mowat Wilson Italian Association, whose parents/guardians will have agreed and signed informed consent for their participation in the study.

Parents/guardians will be asked to answer to a series of questionnaires regarding comprehensive medical and dental history, oral habits, socioeconomic status, and oral-health related quality of life (OHRQoL).

Participants will then undergo intraoral and extraoral examination, extraoral photographs of the face; dental and facial digital scans will be also collected.

Parents/guardians will be asked to provide any dental radiographs of subjects (panoramic dental x-ray, dental computer tomography, lateral skull radiographs for cephalometry) if previously performed .

• Study Type: Observational
• Enrollment (Estimated): 25

Contacts and Locations

• Study Contact: Name: Maria Grazia Cagetti, DDS, MSc, PhD; Phone Number: +39 02503 19008; Email: maria.cagetti@unimi.it
• Study Contact Backup: Name: Araxi Balian, DDS, MSc, PhD; Email: araxibalian@gmail.com

Study Locations

• Italy
  • Milan, Italy
    • University of Milan
    • Contact: Maria Grazia Cagetti, DDS, MSc, PhD; Phone Number: +39 02503 19008; Email: maria.cagetti@unimi.it
    • Contact: Araxi Balian, DDS, MSc, PhD; Email: araxibalian@gmail.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Partecipants will be enrolled from those who will attend the annual meeting of the Italian Mowat Wilson Association

Description

Inclusion Criteria:

• individuals affected by MWS with confirmed molecularly diagnosis of ZEB2 gene variation.
• written informed consent statement signed by parents/legal guardians for participation in the study

Exclusion Criteria:

• individuals not affected by MWS
• refusal of parents/legal guardians to participate in the study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Individuals diagnosed with MWS; Subects affected by MWS with molecularly confirmed diagnosis of ZEB2 gene variation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dental caries assessment	Dental caries will be measured as follows: frequency of individuals with dental caries; distribution of patients' dental caries experience according to the individual DMFT index score (ranging from 0 to 28, where zero is equivalent to "no dental caries experience" and 28 that all teeth have been affected); localization (type of tooth; permanent/decidous teeth) and severity of dental caries according to the ICDAS index (ranging from 0 to 6, where zero is equivalent to "sound tooth" and 6 to "extensive cavity with visible dentin")	Baseline
Facial morphometric assessment	Facial soft tissue characteristics will be measured by 2D and 3D analysis performed on frontal/lateral photographs of the face and 3D face scanning, respectively. Extraoral facial photographs will be used for 2D facial morphometric analysis, both frontal and profile views, using OrthoTP® software (Microlab, Italy). 3D facial morphometric analysis will be performed on the 3D reconstructions of the subjects' facial scans using VAM software (Canfield Scientific, Inc., Parsippany, NJ, USA). The reference landmarks and planes for both 2D and 3D facial morphometric analyses were selected according to international criteria and previously validated protocols that have also been applied in the study of subjects with facial dysmorphisms. The values obtained will be compared with reference values reported in the literature for the general population matched for age and sex.	Baseline
Cephalometric assessment	Dento-skeletal characteristics will be measured by cephalometric analysis performed on lateral skull radiographs of patients, if previously performed and provided by the parents/guardians. Cephalometric tracings and measures will be performed using OrthoTP® software (Microlab, Italy). The cephalometric analysis method that will be adopted is that of the Milan School of Orthodontics, which includes several analyses commonly used in orthodontics and internationally validated.	Baseline
Dental arch assessment	Molar and canine Angle's dental arch relationships, frequency and degree of dental crowding/spacing, dental arch widths (intercanine, interpremolar, and intermolar widths) and depth will be assessed on patient's intraoral digital scans using VAM software (Canfield Scientific, Inc., Parsippany, NJ, USA).	Baseline
Dental anomalies assessment	Frequency and type of dental anomalies (missing and/or suvrannumerary tooth; micro/macrodontia; tooth inclusion; tooth displacement; alterations in tooth morphology) will be assessed during the dental examination and on dental radiographs of subjects (panoramic dental x-ray, dental computer tomography) if provided by the parents/guardians	Baseline
Dental plaque assessment	Mean and distribution of the WHO Plaque Index (PI) will be calculated. PI score can range from 0 to 3 (where 0 is "absence of dental plaque" and 3 is "abundant and visibile dental plaque").	Baseline
Developmental Defects of Enamel (DDEs) assessment	Frequency, type and localization of DDEs will be assessed using the DDE index. The DDE index classifies enamel defects according to their clinical appearance. It categorizes defects into three main types: demarcated opacities, diffuse opacities, and enamel hypoplasia, and also allows the recording of combinations of these defects. The index records the type, distribution, and extent of the defect on each tooth surface, enabling consistent documentation and comparison of enamel developmental defects in clinical and epidemiological study. When the phenotypic appearance will suggest specific alterations consistent with molar-incisor hypomineralization (MIH) or dental fluorosis, specific indices will be used to assess the severity of the lesions (MIH and Dean indexes).	Baseline
Periodontal health assessment	The Community Periodontal Index (CPI) will be used to assess in the 6 sextants of the mouth the parodontal status. The CPI ranges from 0 to 4, where zero stands for "healthy gingiva" and 4 for "deep pocket of 6 mm or more".	Baseline
Oral mucosa lesion assessment	Frequency, type (e.g. abscess, leukoplakia, ulcer, oral candidiasis, etc...), and localization (vermilion borderof the lips, commisure of lips, lips, buccal mucosa, floor of mouth, tongue, palate, gum) of oral mucosal lesion will be assessed.	Baseline
Morphological facial assessment	Frequency of convex and concave facial profile, brachicephalic (short-headed) and dolicocephalic (long-headed) craniofacial shape, decreased and increased lower third of the face, and mandibular and facial asymmetry will be assessed.	Baseline
Occlusal assessment	The frequency of Class I, Class II, Class III, deepbite, openibite, crossbite, and scissorbite malocclusions, increased and/or decreased overjet and overbite, dental crowding, and spacing will be assessed.	Baseline
Oral functional assessment	Frequency and type of oral habits/oral dysfunctions (e.g. oral breathing, tongue thrust, non-sucking habits, sleep apnoea, bruxism, etc...), tonsillar hypertrophy (Mallampati index), soft palate position (Friedman index), and temporomandibular disorders (TMD) will be assessed.	Baseline
Oral Health Realated Quality of Life (OHRQoL)	Oral Health-Related Quality of Life will be assessed using standardized questionnaires: one for subjects up to 17 years of age (P-CPQ Questionnaire) and another for subjects aged 18 years and older (OHIP-14 Questionnaire).	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phenotype and genotype association	Correlation between genotype and phenotype will be investigated by analyzing the association between the dental, occlusal, and facial characteristics observed and the three main genetic variants of mutation of the ZEB2 gene (complete deletion; absence of protein; defective protein) through Chi-squared and Fisher's exact tests.	Baseline

Collaborators and Investigators

• Sponsor: University of Milan
• Collaborators: Associazione Italiana Mowat Wilson (Mowat Wilson Italian Association)

Publications and helpful links

General Publications

• Ivanovski I,Djuric O,Broccoli S,Caraffi SG,Accorsi P,Adam MP,Avela K,Badura-Stronka M,Bayat A,Clayton-Smith J,Cocco I,Cordelli DM,Cuturilo G,Di Pisa V,Dupont Garcia J,Gastaldi R,Giordano L,Guala A,Hoei-Hansen C,Inaba M,Iodice A,Nielsen JEK,Kuburovic V,Lazalde-Medina B,Malbora B,Mizuno S,Moldovan O,Møller RS,Muschke P,Otelli V,Pantaleoni C,Piscopo C,Poch-Olive ML,Prpic I,Marín Reina P,Raviglione F,Ricci E,Scarano E,Simonte G,Smigiel R,Tanteles G,Tarani L,Trimouille A,Valera ET,Schrier Vergano S,Writzl K,Callewaert B,Savasta S,Street ME,Iughetti L,Bernasconi S,Giorgi Rossi P,Garavelli L
• Hart TC,Hart PS
• Salerno C,D'Avola V,Oberti L,Almonte E,Bazzini EM,Tartaglia GM,Cagetti MG
• Mowat DR,Croaker GD,Cass DT,Kerr BA,Chaitow J,Adès LC,Chia NL,Wilson MJ
• Meazzini MC, Demonte LP, Conti L, Autelitano L, Cohen N, Mazzoleni F. The role of the dentist and the orthodontist in early diagnosis of Gorlin-Goltz syndrome: a cephalometric and photometric study. Eur J Paediatr Dent. 2023 Jun 1;24(2):161-165. doi: 10.23804/ejpd.2023.24.02.03.
• Dolci C, Sansone VA, Gibelli D, Cappella A, Sforza C. Distinctive facial features in Andersen-Tawil syndrome: A three-dimensional stereophotogrammetric analysis. Am J Med Genet A. 2021 Mar;185(3):781-789. doi: 10.1002/ajmg.a.62040. Epub 2020 Dec 24.
• Dolci C, Pucciarelli V, Gibelli DM, Codari M, Marelli S, Trifiro G, Pini A, Sforza C. The face in marfan syndrome: A 3D quantitative approach for a better definition of dysmorphic features. Clin Anat. 2018 Apr;31(3):380-386. doi: 10.1002/ca.23034. Epub 2017 Dec 23.
• Pachajoa H, Gomez-Pineda E, Giraldo-Ocampo S, Lores J. Mowat-Wilson Syndrome as a Differential Diagnosis in Patients with Congenital Heart Defects and Dysmorphic Facies. Pharmgenomics Pers Med. 2022 Nov 1;15:913-918. doi: 10.2147/PGPM.S380908. eCollection 2022.
• Garavelli L, Zollino M, Mainardi PC, Gurrieri F, Rivieri F, Soli F, Verri R, Albertini E, Favaron E, Zignani M, Orteschi D, Bianchi P, Faravelli F, Forzano F, Seri M, Wischmeijer A, Turchetti D, Pompilii E, Gnoli M, Cocchi G, Mazzanti L, Bergamaschi R, De Brasi D, Sperandeo MP, Mari F, Uliana V, Mostardini R, Cecconi M, Grasso M, Sassi S, Sebastio G, Renieri A, Silengo M, Bernasconi S, Wakamatsu N, Neri G. Mowat-Wilson syndrome: facial phenotype changing with age: study of 19 Italian patients and review of the literature. Am J Med Genet A. 2009 Mar;149A(3):417-26. doi: 10.1002/ajmg.a.32693.
• Ivanovski I, Djuric O, Caraffi SG, Santodirocco D, Pollazzon M, Rosato S, Cordelli DM, Abdalla E, Accorsi P, Adam MP, Ajmone PF, Badura-Stronka M, Baldo C, Baldi M, Bayat A, Bigoni S, Bonvicini F, Breckpot J, Callewaert B, Cocchi G, Cuturilo G, De Brasi D, Devriendt K, Dinulos MB, Hjortshoj TD, Epifanio R, Faravelli F, Fiumara A, Formisano D, Giordano L, Grasso M, Gronborg S, Iodice A, Iughetti L, Kuburovic V, Kutkowska-Kazmierczak A, Lacombe D, Lo Rizzo C, Luchetti A, Malbora B, Mammi I, Mari F, Montorsi G, Moutton S, Moller RS, Muschke P, Nielsen JEK, Obersztyn E, Pantaleoni C, Pellicciari A, Pisanti MA, Prpic I, Poch-Olive ML, Raviglione F, Renieri A, Ricci E, Rivieri F, Santen GW, Savasta S, Scarano G, Schanze I, Selicorni A, Silengo M, Smigiel R, Spaccini L, Sorge G, Szczaluba K, Tarani L, Tone LG, Toutain A, Trimouille A, Valera ET, Vergano SS, Zanotta N, Zenker M, Conidi A, Zollino M, Rauch A, Zweier C, Garavelli L. Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care. Genet Med. 2018 Sep;20(9):965-975. doi: 10.1038/gim.2017.221. Epub 2018 Jan 4.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): August 30, 2026

Study Registration Dates

• First Submitted: March 6, 2026
• First Submitted That Met QC Criteria: March 11, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: malocclusion; oral health; dental caries; periodontal diseases; Craniofacial Abnormalities; Mowat-Wilson syndrome
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Mouth Diseases; Stomatognathic Diseases; Musculoskeletal Abnormalities; Stomatognathic System Abnormalities; Congenital Abnormalities; Tooth Demineralization; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Malocclusion; Tooth Diseases; Periodontal Diseases; Dental Caries; Tooth Abnormalities; Craniofacial Abnormalities; Mowat-Wilson syndrome
• Other Study ID Numbers: EC University of Milan 126/25

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual de-identified patient data will be shared on the respository UNIMI Dataverse
• IPD Sharing Time Frame: All requests for data relating to this study that are made within 5 years from data collection will be considered.

IPD Sharing Access Criteria

IPD generated during the study will be made available through the University of Milan Data Repository (UNIMI Dataverse).

Only fully anonymized datasets will be shared to ensure the protection of participants' privacy and compliance with applicable data protection regulations.

No information that could directly or indirectly identify individual participants will be included.

Researchers interested in accessing the dataset will be able to submit a request through the UNIMI Dataverse platform, specifying the intended use of the data. Datasets will be accessible via the UNIMI Dataverse repository interface, where users will be required to agree to the repository's data use terms and conditions before downloading the files.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No