Oral findings and comprehensive dental management of Moebius syndrome: a systematic review

**Background:** Moebius syndrome (MS) is a rare, non-progressive, congenital neuromuscular disorder characterized by paralysis of the abducens (VI) and facial (VII) cranial nerves, often with asymmetric presentations. It occurs in approximately 1/100,000 live births with no gender predilection. The etiopathogenesis remains unclear, with theories including ischemic disruption of brainstem vascular supply and embryological developmental defects. Mutations in MBS1, MBS2, MBS3, and HOX family genes have been implicated. Clinical presentation varies depending on the extent of paralysis and anatomical structures involved, frequently including craniofacial and orolingual malformations. This systematic review aimed to describe oral and extraoral findings in MS patients and their comprehensive dental management.

**Methods:** A digital search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar, restricted to English-language articles published from January 1, 2000, to April 2, 2023, following PRISMA guidelines. The SPIDER question format was used: Sample (Moebius syndrome patients), Phenomena of Interest (oral and extraoral manifestations), Design (clinical case reports), Evaluation (dental management), Research type (qualitative). Inclusion criteria were clinical studies, case series, and case reports with confirmed MS cases and sufficient clinical information for definitive diagnosis, focusing on dental management. Book chapters, editorials, and short communications were excluded. Quality assessment was performed using JBI guidelines for case reports and case series, with risk of bias classified as high (≤49% 'Yes' scores), moderate (50-69%), or low (≥70%). Data extraction included year, first author, country, number of cases, study design, age, gender, oral and extraoral manifestations, dental treatment, dental discipline, and follow-up period. Descriptive statistics were calculated using STATA V15.

**Key Results:** From 3,172 initial articles, 23 studies (18 case reports, 5 case series) comprising 124 MS patients were included. The mean age was 14.92 ± 12.80 years (range 0.5-49 years), with 82% of patients younger than 15 years. Males were more affected (64%), with a male-to-female ratio of 2:1. The most frequent extraoral manifestations were blinking and visual problems (78.22%), malformations of the upper and lower limbs (58.87%), bilateral facial paralysis (12.90%), lack of facial expression (12.09%), and unilateral facial paralysis (6.45%). The most frequent oral manifestations were tongue deformities (78.22%), micrognathia (37.90%), labial incompetence (36.29%), cleft palate (33.87%), gothic palate (16.12%), microstomia (15.32%), anterior open bite (15.32%), dental caries (8.87%), and periodontal disease (8.06%). Dental management was most commonly provided by pediatric dentistry (60.86%), using a surgical approach (56.52%), orthodontic and maxillary orthopedic treatment (43.47%), restorative treatment (39.13%), and periodontal treatment (21.73%). Follow-up data were available for some studies, with a mean follow-up of 3.74 ± 3.22 years. All included studies had low risk of bias according to JBI criteria.

**Clinical Implications:** This systematic review highlights the wide variety of oral and extraoral manifestations in MS patients, necessitating a multidisciplinary dental approach. The high prevalence of tongue deformities, micrognathia, and labial incompetence underscores the need for early orthodontic and surgical interventions. The frequent occurrence of dental caries and periodontal disease emphasizes the importance of preventive care and regular dental follow-up. Dental treatments must be tailored to each patient's specific manifestations, with considerations for microstomia, limited mouth opening, and potential behavioral challenges. The review also notes that patients with MS may require general anesthesia or sedation for comprehensive oral rehabilitation, but careful airway management is essential due to micrognathia and microstomia. Overall, a comprehensive dental treatment plan covering both problem resolution and oral health maintenance is crucial for improving quality of life in MS patients.