Phenotypic variations of macrostomia
- 4 distinct variations: complete lateral facial cleft, simple macrostomia, macrostomia with diastasis of the facial musculature, and isolated facial musculature diastasis
- Different physical appearances and varying levels of severity for each variation
- Abnormalities involve skin, subcutaneous tissue, facial muscles, and mucous membrane
- Severity of abnormalities can range from minor to severe

Complete lateral facial cleft
- Cleft runs from corner of the mouth towards the bottom of the ear
- Outside of the ear on affected side appears normal
- Region of soft tissue connects the cleft to the right lateral posterior hard palate
- No soft palate internally
- Severe form of macrostomia

Simple macrostomia
- Less severe form of macrostomia
- Does not affect facial muscles
- Not associated with soft tissue or bone deformities
- Small cleft(s) extend from the mouth and can be surgically repaired
- Relatively milder physical appearance

Diastasis of the facial musculature
- Clefts slightly more severe than in simple macrostomia
- No bone deformities, but minor soft tissue deformities present
- Muscle diastasis, particularly separation of the masseter, is the defining feature
- Partial correction possible through surgery
- Moderate physical appearance

Isolated facial musculature diastasis
- More severe muscle separation, but no true open cleft
- Bones in the region remain unaffected
- Phenotype appears as indentation of the cheek
- External ear can also be deformed
- Relatively severe form of macrostomia

Mechanism and Genetic factors
- No definitive mechanism to explain macrostomia's development
- Likely interactions between genes and the environment
- Improper development of the first and sometimes second brachial arch
- Complex nature of macrostomia leads to various theories
- Environmental contaminants may play a role in causing macrostomia
- Macrostomia classified as a heritable autosomal dominant disease
- Responsible mutation found on the short arm of chromosome 1 (1p32-1p34)
- Heterozygous mutation in the gene PTCH2 (Val147Ile)
- PTCH2 encodes a transmembrane protein involved in inhibiting the sonic hedgehog signaling pathway
- Loss of function mutation leads to a lack of control of cell growth during development

Macrostomia (Wikipedia)

Macrostomia refers to a mouth that is unusually wide. The term is from the Greek prefix makro- meaning "large" and from Greek στόμα, "mouth".

Macrostomia
Macrostomia from bilateral mouth fissures
Specialty	Medical genetics

Macrostomia is characterized as a physical abnormality that causes clefts to form on the face of affected individuals. These clefts can form on either or both sides of the face, but they are most commonly seen on the right cheek and have a higher rate of occurrence in males. Macrostomia is very irregular and on average occurs only once in every 150,000 to 300,000 live births. It's unusual for macrostomia to occur on its own and it is included as a symptom for many diseases including craniofacial microsomia. The clefts result from improper development and fusion of the mandibular and maxillary processes. The clefts cause problems with facial muscle development. The origin of macrostomia is not yet fully understood: it could have multiple causes.