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.

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.