Macrostomia refers to a

mouth In animal anatomy, the mouth, also known as the oral cavity, or in Latin cavum oris, is the opening through which many animals take in food and issue vocal sounds. It is also the cavity lying at the upper end of the alimentary canal, bounded on ...

that is unusually wide. The term is from the Greek prefix ''makro-'' meaning "large" and from Greek στόμα, "mouth".στόμα
Henry George Liddell, Robert Scott, ''A Greek-English Lexicon'', on Perseus 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

maxilla The maxilla (plural: ''maxillae'' ) in vertebrates is the upper fixed (not fixed in Neopterygii) bone of the jaw formed from the fusion of two maxillary bones. In humans, the upper jaw includes the hard palate in the front of the mouth. The t ...

ry processes. The clefts cause problems with facial muscle development. The origin of macrostomia is not yet fully understood: it could have multiple causes.

Phenotypic variations

There are 4 distinct variations of macrostomia. Classifications are a complete lateral facial cleft, simple macrostomia, macrostomia with diastasis of the facial musculature, and isolated facial musculature diastasis. Each has a different physical appearance with varying levels of severity. The cleft associated with macrostomia is associated with improper or failed fusion of the mandibular and maxillary processes during embryonic development. This can lead to a variety of abnormalities involving

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...

subcutaneous tissue The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The types of cells found in the layer are fibroblasts, adipose cells, and macr ...

, facial muscles, and the mucous membrane. The severity of each abnormality can vary from minor to severe. Environmental contaminants may play a role in causing macrostomia. Many affected individuals were found in Lagos, an industrial area of Nigeria, where water supplies are known to be contaminated by improper disposal of industrial and domestic waste.

Complete lateral facial cleft

The facial cleft runs from the corner of the mouth towards the bottom of the ear. The outside of the ear on the affected side of the face appears as normal and a region of soft tissue connects the cleft to the right lateral posterior hard palate. Internally there is no soft palate.

Simple macrostomia

This version of macrostomia is less severe because it does not affect the facial muscles and is not associated with any soft tissue or bone deformities. A small cleft(s) extends from the mouth and can be repaired surgically.

Diastasis of the facial musculature

Clefts in this variant are slightly more severe than the ones seen in simple macrostomia. It also does not have bone deformities, but it does include minor soft tissue deformities. The defining feature is muscle diastasis which is separation of the masseter. This phenotype can also be partially corrected with surgery.

Isolated facial musculature diastasis

The facial cleft in this case results in a more severe muscle separation even though there is not a true open cleft. Bones in the region remain unaffected and the phenotype appears as an indentation of the cheek rather than an open cleft. The external ear in this phenotype can also be deformed.

Mechanism

Likely due to the complexity of macrostomia, many theories have been provided over time in an attempt to define its origin. There is no definitive mechanism to explain its development but it is likely that there are interactions between genes and the environment resulting in improper development of the first and sometimes second brachial arch.

Genetic

Macrostomia can be partially classified as a heritable autosomal dominant disease. The responsible mutation is found on the short arm of chromosome 1 in

locations In geography, location or place are used to denote a region (point, line, or area) on Earth's surface or elsewhere. The term ''location'' generally implies a higher degree of certainty than ''place'', the latter often indicating an entity with an ...

32-34 (1p32-1p34). The mutation is

heterozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

meaning that it only occurs in one

allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...

. A single base substitution in the 11th

coding region The coding region of a gene, also known as the coding sequence (CDS), is the portion of a gene's DNA or RNA that codes for protein. Studying the length, composition, regulation, splicing, structures, and functions of coding regions compared to no ...

of the gene

PTCH2 Patched 2 is a protein that in humans is encoded by the PTCH2 gene. Function This gene encodes a transmembrane receptor of the patched gene family. The encoded protein may function as a tumor suppressor in the hedgehog signaling pathway. Clin ...

changes an

adenine Adenine () ( symbol A or Ade) is a nucleobase (a purine derivative). It is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The three others are guanine, cytosine and thymine. Its derivati ...

guanine Guanine () ( symbol G or Gua) is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine (uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside is called ...

. This results in a

valine Valine (symbol Val or V) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α- carboxylic acid group (which is in the deprotonat ...

being incorporated instead of an

isoleucine Isoleucine (symbol Ile or I) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the deprot ...

at the 147th position during

translation Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...

of the resulting

transmembrane protein A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...

(Val147Ile). The transmembrane protein encoded by PTCH2 is 1204

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

s long and is involved with inhibiting the

sonic hedgehog Sonic hedgehog protein (SHH) is encoded for by the ''SHH'' gene. The protein is named after the character ''Sonic the Hedgehog''. This signaling molecule is key in regulating embryonic morphogenesis in all animals. SHH controls organogenesis and ...

signalling pathway that is involved with development. PTCH2 inhibits the smooth frizzled class receptor (SMO) which when active is responsible for increasing transcription rates of many genes involved with development and differentiation. PTCH2 (Val147Ile) is a loss of function mutation which results in a lack of control of

cell growth Cell growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis (production of biomolecules or anabolism) is greater than ...

during development and links it to macrostomia.

References

External links

{{Congenital malformations and deformations of ear, face and neck Congenital disorders of eye, ear, face and neck