Treatment for "Asymmetric Crying Facies"

A Randomized, Double-Blind, Controlled Study Evaluating the Efficacy of Botulinum Toxin Type A (Hengli) Injection for LowerLip Asymmetry in Children With Craniofacial Microsomia

This study focuses on children with hemifacial microsomia (HFM), a common congenital craniofacial deformity caused by abnormal development of the first and second branchial arches. Up to 45% of children with HFM have facial nerve dysplasia, most frequently involving the mandibular marginal branch. These children present with asymmetric lower-lip movement called "crooked-mouth smile" during smiling, speaking or crying. Unlike asymmetric crying syndrome, this condition does not resolve spontaneously and may gradually get worse.

"Crooked-mouth smile" results from muscle weakness of the lower lip on the affected side, leading to dynamic perioral muscle imbalance. Static treatment includes botulinum toxin injection, muscle resection, nerve cutting and fascia suspension; dynamic treatment includes muscle transfer procedures. Early intervention is important for children's psychological well-being. Botulinum toxin injection is minimally invasive, safe and reversible, and is regarded as a preferred initial therapy. However, prospective clinical evidence regarding its efficacy, safety and appropriate dosage in this pediatric population remains insufficient. This prospective study aims to explore the safety, effectiveness and optimal dose of botulinum toxin injection for treating "crooked-mouth smile" in children with HFM and mandibular marginal branch dysplasia.

Study Overview

• Status: Recruiting
• Conditions: Facial Nerve Paralysis; Hemifacial Microsomia
• Intervention / Treatment: Procedure: Botulinium toxin type A injection

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiaoshuang Guo, M.D.; Phone Number: +86 13121234163; Email: gxsinjnu@126.com

Study Locations

• China
  • China
    • Beijing, China, China, 100144
      • Recruiting
      • Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
      • Contact: Xiaoshuang Guo, M.D.; Phone Number: +86 13121234163; Email: gxsinjnu@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Children under 18 years old diagnosed with hemifacial microsomia (HFM) and lower-lip asymmetry, with congenital injury of the marginal mandibular branch of the facial nerve, presenting with lower-lip movement disorder and lower-lip asymmetry during smiling and teeth-baring.
2. Subjects who are able to comply with study protocols and visit schedules.
3. Subjects whose guardians provide voluntary written informed consent.

Exclusion Criteria:

1. Any disease affecting neuromuscular function, including but not limited to neuromuscular junction disorders such as myasthenia gravis and Lambert-Eaton syndrome, peripheral motor nerve diseases such as amyotrophic lateral sclerosis, or a past medical history of the above-mentioned diseases.

2. Receiving treatment with any of the following medications:

   1. Within 4 weeks prior to screening: muscle relaxants (tubocurarine chloride, dantrolene sodium, baclofen, etc.), aminoglycosides, polypeptide antibiotics, spectinomycin hydrochloride, tetracyclines, lincomycin, anticholinergic agents (butylscopolamine bromide, trihexyphenidyl hydrochloride, etc.), benzodiazepines, and other drugs that may inhibit neuromuscular transmission or interfere with the effect of botulinum toxin.
   2. Anticoagulants or anti-platelet agents used within 7 days before study drug administration.
3. Cutaneous abnormalities at the treatment site, including local infection (e.g., herpes simplex, acne, erysipelas), scars, hypertrophic scars, or keloid predisposition.
4. Prior perioral treatment within 1-year interval before this study.
5. History of hypersensitivity; known allergy to any component of the investigational or comparator product, or known sensitivity to complex protein components (including botulinum toxin type A, human albumin, gelatin protein, lactose, sodium chloride, or sodium succinate).
6. Presence of other comorbidities that render the subject inappropriate for enrollment at the investigator's discretion. Eligibility shall be determined by the investigator.
7. Participation in another clinical trial (drug or device-related) at the time of screening, or participation in any other clinical trial within 30 days before screening.
8. Subjects unable to communicate or incapable of following study instructions.
9. Staff members of the study department or sponsor.
10. Subjects considered unsuitable for participation in this study by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Group; Participants receive botulinum toxin injection immediately after enrollment for correction of crooke	Procedure: Botulinium toxin type A injection; Injection targets the "depressor labii inferioris" and "depressor anguli oris" for correction of crooked-mouth smile.
Active Comparator: Control Group (Delayed Treatment); articipants do not receive botulinum toxin injection at baseline. After completing 6-month follow-up assessment for primary outcomes, subjects in this group will receive botulinum toxin injection.	Procedure: Botulinium toxin type A injection; Injection targets the "depressor labii inferioris" and "depressor anguli oris" for correction of crooked-mouth smile.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mouth asymmetry	A coordinate system is established based on the palpebral fissure and nasion. The sagittal distance differences at the hemilabial midpoint and oral commissure point are evaluated under static, broad-smile, and teeth-baring conditions in children	1、3、6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
satisfaction with lips	Face-Q: satisfaction with lips. FACE-Q Aesthetics: Satisfaction with Lips scale. Patient-reported satisfaction with lip appearance. Rasch-transformed scores range from 0 to 100; higher scores indicate greater satisfaction (better outcome).	1、3、6 months
Terzis aesthetic and functional grading system for the depressor muscle	Investigator-assessed depressor muscle aesthetic and functional performance using the Terzis aesthetic and functional grading system for the depressor muscle. Scores range from 0 (Poor, total paralysis) to 2 (Excellent, normal symmetric lower-lip movement); higher scores indicate better aesthetic and functional outcomes.	1、3、6 months
Smile Improvement Score	Investigator-assessed improvement in smile aesthetics using the Smile Improvement Score (SIS), a subjective grading system for lip posture during smile. Frontal smile photographs are compared with baseline; scores range from 0(no improvement) to 3 (excellent improvement, symmetric smile); higher scores indicate better smile outcome.	1、3、6 months

Collaborators and Investigators

• Sponsor: Peking Union Medical College

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: August 30, 2026
• First Submitted That Met QC Criteria: August 30, 2026
• First Posted (Actual): September 3, 2026

Study Record Updates

• Last Update Posted (Actual): September 10, 2026
• Last Update Submitted That Met QC Criteria: September 6, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Botulinum toxin; Hemifacial microsomia; Facial nerve dysplasia; Crooked-mouth smile
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Mouth Diseases; Stomatognathic Diseases; Nervous System Diseases; Infections; Virus Diseases; DNA Virus Infections; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Congenital Abnormalities; Herpesviridae Infections; Cranial Nerve Diseases; Bone Diseases, Developmental; Facial Nerve Diseases; Dysostoses; Craniofacial Dysostosis; Mandibulofacial Dysostosis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Bell Palsy; Goldenhar Syndrome
• Other Study ID Numbers: 2024(170)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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