Hemifacial microsomia is linked to a rare homozygous variant V162I in FRK and validated in zebrafish.

OBJECTIVES: Hemifacial microsomia (HFM) is a common birth defect involving the first and second branchial arch derivatives. Although several chromosomal abnormalities and causal gene variants have been identified, genetic etiologies in a majority of cases with HFM remain unknown. This study aimed to identify genetic mutations in affected individuals with HFM. METHODS: Whole-exome sequencing and bioinformatics analysis were performed for 16 affected individuals and their family members. Sanger sequencing was applied for confirmation of selected mutations. Zebrafish embryos were used for in situ hybridization of candidate gene, microinjection with antisense morpholino, and cartilage staining. RESULTS: A homozygous missense mutation (c.484G > A; p.V162I) in the FRK gene was identified in an 18-year-old girl with HFM and dental abnormalities. Heterozygous mutation of this mutation was identified in her parents, who are first cousins in a consanguineous family. FRK is highly expressed in the Meckel's cartilage during embryonic development in mouse and zebrafish. Knockdown of frk in zebrafish showed a lower length and width ratio of Meckel's cartilage, abnormal mandibular jaw joint, and disorganized ceratobranchial cartilage and bone. CONCLUSIONS: We identified a recessive variant in the FRK gene as a novel candidate gene for a patient with HFM and mandibular hypoplasia and revealed its effects on craniofacial and embryonic development in zebrafish.

Reconstruction of large defects of anterior floor of mouth with free flaps using a novel individualized flap design method.

The purpose of this study was to introduce a novel individualized flap design method for large anterior floor of the mouth (AFOM) defect reconstruction, review experience with the use of this flap design method for large AFOM defect reconstruction, and assess its functional results. A retrospective study of patients who received large AFOM defect reconstruction with free flaps was conducted. There was a cohort of patients who were treated using the novel individualized flap design method and a cohort without flap design. Functional outcomes were evaluated with appropriate scales. Outcomes were analyzed, and a p-value <0.05 was considered significant. 22 patients received the individualized flap design, while 21 patients were treated without a special flap design. All flaps survived. All free flaps harvested with the novel individualized flap design method better matched AFOM defects. Relative to patients without flap design, patients in the novel individualized flap design group showed significant improvement in speech intelligibility (p = 0.036) and swallowing function (p = 0.019). Within the limitation of the study it seems that large AFOM defect reconstruction with the novel individualized flap design method can not only cover and close the wound to avoid oral-neck fistulae, but also maintains tongue mobility to achieve better functional outcomes than in patients without flap design.

A novel flap design technique for subtotal tongue reconstruction with an "Individualized and Convenient Tongue Model".

BACKGROUND: To achieve improved functional outcomes in subtotal tongue reconstruction, a flap design with sufficient volume and appropriate shape is necessary. In this study, we introduce an "Individualized and Convenient Tongue Model" (ICTM) for flap design in subtotal tongue reconstruction. METHODS: By studying the anatomical morphology of the tongue, we found a similar geometry within the dorsum and body of the tongue as well as the mouth floor. This can be used to create an ICTM through folding and splicing. We can simulate tongue defects in the ICTM and transform defect shapes into guide plates for flap design. In this study, fifty-eight patients requiring subtotal tongue reconstruction were randomly divided into two groups: an ICTM group (35 patients) and a conventional group (31 patients). In the ICTM group, we individually designed profunda artery perforator flaps (PAPFs) or anterolateral thigh flaps (ALTFs) using the ICTM method. In the conventional group, the flap was designed according to the surgeon's clinical experience. Patient demographics, operative and follow-up data were recorded. Swallowing, speech intelligibility, and cosmetic results were assessed using appropriate scales. RESULTS: All flaps survived, although there were no significant differences in tumor size, operation time, flap size, and complication rate compared to the conventional group. Patients in the ICTM group had significantly improved speech intelligibility (p = 0.019), cosmetic appearance (p = 0.009), and swallowing ability (p = 0.003). CONCLUSIONS: The ICTM technique is an effective and convenient solution for subtotal tongue reconstruction that provides an individualized flap design and improves functional outcomes compared to the conventional design.