A 23-year-old female was admitted to our hospital due to severe mandibular malformations and poor occlusion accompanied by severe sleep snoring for more than 20 years. With the increase of age, the deformity becomes more and more severe. The physical examination of the patient revealed facial asymmetry, a round face with prominent cheeks (severe on the right), retrognathia and mandibular hypoplasia, presenting as a typical ‘beak deformity’ (Fig. 1A-C). Computed tomography (CT) of the skull revealed that mandibular body, rami, and bilateral condyles were marked hypoplasia, and lateral bony prominence of the bilateral mandible was observed (Fig. 1D-F). The bilateral parotid glands were small and ectopic towards the front edge of the masseter muscle (as indicated by red dashed lines in Fig. 1G).
Intraoral examination revealed crowded teeth, malocclusion, and malalignment. The patient presented with an approximate Class Ⅰ molar relation, overbite and overjet in anterior teeth, left-side posterior cross-bite (Fig. 1H-M). The interincisal distance was 30 mm, indicating limited mouth opening, but there was no clicking sound or tenderness in the area of bilateral temporomandibular joints (TMJs). No distinct cleft or notching between the lobe and helix were found, morphology and function of middle and inner ears were normal.
Polysomnography revealed an apnea hypopnea index of 10.8, manifesting as low-grade obstructive sleep apnea syndrome and moderate hypoxemia. Her physical and mental development was normal, and she had no speech and learning problems. Family history revealed that her younger brother had similar symptoms (Fig. 2), whereas their proband were healthy and did not exhibit any facial abnormality. Whole exome sequencing revealed that the patient and the patietnt’s younger brother harbroured a novel insertional mutation in GNAI3 (Table 1). The 3D molecular structure prediction of the protein and the disruption of hydrogen bonds are depicted in Fig. 3.
Table 1
The results of the patient’s whole exome sequencing.
Mutated gene | Chromosomal location | Transcript | Exon | Nucleotide change | Amino acid change | Diagnosis | Source of mutation |
GNAI3 | chr1:110116384 | NM_006496 | exon 2 | c.144_145insCATTGTGAAACAGATGAA | p.T48_I49insHCETDE | ACSND I | Father |
Based on the patient’s clinical presentation and molecular diagnosis, the patient was diagnosed with ARCND Ⅰ, OSAS and moderate hypoxemia. The patient's principal problem to be addressed were convexity of midface and micrognathia deformity. Hypoplasia of the condylar and reduced rami induced retrognathism and clockwise rotation of the mandibular.
In April 2016, after consultation with orthodontist, a sequential treatment plan consisting of orthodontic treatment and craniofacial surgery with the aid of of digital technology was established. During the preoperative orthodontic treatment, teeth 12 (located outside of the lingual dental arch), 21 (tooth with dead pulp), 33 (affected by severe periodontal disease), and tooth 44 were extracted. Additionally, we aligned the crowed teeth and leveled the dentition to minimize tooth compensation.
After the preoperative orthodontic treatment was completed, distraction osteogenesis (DO) was performed using a virtual surgical plan and surgical guides via submandibular incision in July 2017. Four distractors were placed bilaterally in the mandible to lengthen the body and rami respectively (Fig. 4A-D). After a latent period of 5 days, the distractors were activated at a rate of 0.5mm twice daily. After the distraction phase, the left and right mandibular rums were extended by 15 and 10mm separately, while the left and right mandibular body was extended by 24 and 19mm, respectively.
Six months after DO, the patient underwent orthognathic surgery in January 2018. At that time, the patient’s front teeth were repositioned; however, the maxillary occlusal plane was still low on the left side and high on the right side. Maxillary Le Fort I osteotomy was performed to rotate the maxilla counterclockwise, achieving a central incisal cusp movement of 3mm forward and 2mm upward. This achieved a 4 mm drop of the mesial buccal cusp of tooth 16 and a 3 mm drop of the mesial buccal tip of tooth 26. Meanwhile, a bilateral sagittal split ramus osteotomy (BSSRO) was performed to coordinate the jaw bones and achieve a better occlusion. Finally, horizontal osteotomy and genioplasty were performed simultaneously (Fig. 4E-G).
In September 2018, the patient underwent a final surgery including mandibular contouring and removal of buccal fat to achieve a better facial profille. The patient continued orthodontic treatment until achieving stable and optimal occlusion in October 2019.
Treatment results and follow-up
After the treatment, the patient showed a symmetric facial appearance with well-defined facial contour. The mandible was fully extended, both horizontally and vertically, and the mismatch between the jaw and teeth was corrected. An approximate posterior Class I relationship was achieved, and the anterior overjet is relatively small (Fig. 5). A marked improvement of the mandibular range of movement was observed, with a maximal opening capacity of 40 mm. The 3D reconstruction of the airway volume increased from 18,672 mm3 preoperatively to 32,880 mm3 postoperatively (Fig. 6). Snoring symptom completely disappeared during sleep. No complications or discomfort were encountered during the follow-up period, and the patient and their family members were satisfied with the results.