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A cleft lip contains an opening in the
upper lip Lips are a visible body part at the mouth of many animals, including humans. Lips are soft, movable, and serve as the opening for food intake and in the articulation of sound and speech. Human lips are a tactile sensory organ, and can be an e ...
that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the
palate The palate () is the roof of the mouth In animal anatomy Anatomy (Greek ''anatomē'', 'dissection') is the branch of biology concerned with the study of the structure of organism In biology, an organism (from Ancient Greek, Greek: ...

palate
(the roof of the mouth) contains an opening into the
nose A nose is a protuberance in vertebrates that houses the nostrils, or nares, which receive and expel air for Respiration (physiology), respiration alongside the mouth. Behind the nose are the olfactory mucosa and the Paranasal sinus, sinuses. Be ...

nose
. The term orofacial cleft refers to either condition or to both occurring together. These disorders can result in feeding problems, speech problems, hearing problems, and frequent ear infections. Less than half the time the condition is associated with other disorders. Cleft lip and palate are the result of tissues of the face not joining properly during
development Development or developing may refer to: Arts *Development hell, when a project is stuck in development *Filmmaking#Development, Filmmaking, development phase, including finance and budgeting *Development (music), the process thematic material i ...

development
. As such, they are a type of
birth defect A birth defect, also known as a congenital disorder, is a condition present at birth Birth is the act or process of bearing or bringing forth offspring, also referred to in technical contexts as parturition. In mammals, the process is initiat ...
. The cause is unknown in most cases.
Risk factor In epidemiology, a risk factor or determinant is a variable associated with an increased risk of disease or infection. Due to a lack of harmonization across disciplines, determinant, in its more widely accepted wiktionary:determine, scientific m ...
s include ,
diabetes Diabetes mellitus, commonly known as just diabetes, is a group of metabolic disorders characterized by a hyperglycemia, high blood sugar level over a prolonged period of time. Symptoms often include frequent urination, Polydipsia, increased th ...
,
obesity Obesity is a medical condition A disease is a particular abnormal condition that negatively affects the structure or function (biology), function of all or part of an organism, and that is not due to any immediate external injury. ...

obesity
, an older mother, and certain
medications A medication (also referred to as medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug File:Aspirine macro shot.jpg, Uncoated aspirin Tablet (pharmacy), tablets, consisting of about 90% acetylsalicylic acid, along with a ...
(such as some used to treat
seizures An epileptic seizure, formally known as a seizure, is a period of symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temp ...
). Cleft lip and cleft palate can often be diagnosed during pregnancy with an ultrasound exam. A cleft lip or palate can be successfully treated with surgery. This is often done in the first few months of life for cleft lip and before eighteen months for cleft palate.
Speech therapy Speech is human vocal communication Communication (from Latin ''communicare'', meaning "to share" or "to be in relation with") is "an apparent answer to the painful divisions between self and other, private and public, and inner thought and ...
and dental care may also be needed. With appropriate treatment, outcomes are good. Cleft lip and palate occurs in about 1 to 2 per 1000 births in the
developed world A developed country (or industrialized country, high-income country, more economically developed country (MEDC), advanced country) is a sovereign state that has a high quality of life, developed economy and advanced technological infrastructu ...
. Cleft lip is about twice as common in males as females, while cleft palate without cleft lip is more common in females. In 2017, it resulted in about 3,800 deaths globally, down from 14,600 deaths in 1990. The condition was formerly known as a "hare-lip" because of its resemblance to a
hare Hares and jackrabbits are Leporidae, leporids belonging to the genus ''Lepus''. Hares are classified in the same Family (biology), family as rabbits. They have similar herbivorous diets, but are generally larger in size than rabbits, have proport ...

hare
or rabbit, but that term is now generally considered to be offensive.


Signs and symptoms


Cleft lip

If the cleft does not affect the palate structure of the mouth, it is referred to as cleft lip. Cleft lip is formed in the top of the lip as either a small gap or an indentation in the lip (partial or incomplete cleft), or it continues into the nose (complete cleft). Lip cleft can occur as a one-sided (unilateral) or two-sided (bilateral) condition. It is due to the failure of fusion of the
maxillary prominence :''For the cranial structure, see Maxillary process of inferior nasal concha.'' Continuous with the dorsal end of the Pharyngeal arch#First arch, first pharyngeal arch, and growing forward from its cephalic border, is a triangular process, the maxi ...
and medial nasal processes (formation of the primary palate). File:CleftLip1.svg, Unilateral incomplete File:Cleftlip2.svg, Unilateral complete File:CleftLip3.png, Bilateral complete A mild form of a cleft lip is a microform cleft. A microform cleft can appear as small as a little dent in the red part of the lip or look like a scar from the lip up to the nostril. In some cases muscle tissue in the lip underneath the scar is affected and might require reconstructive surgery. It is advised to have newborn infants with a microform cleft checked with a
craniofacial teamCraniofacial surgery is a surgical subspecialtyA subspecialty or subspeciality (British English) is a narrow field of professional knowledge/skills within a specialty of trade (occupation), trade, and is most commonly used to describe the increasingl ...
as soon as possible to determine the severity of the cleft. File:13900470_3PREOPERATION0.jpg, Six-month-old girl before going into surgery to have her unilateral complete cleft lip repaired File:10-month-old_girl_showing_scar_from_facial_reconstruction_surgery_for_cleft_lip.jpg, The same girl, 1 month after the surgery File:8-year-old_girl_showing_scar_from_infantile_facial_reconstruction_surgery.jpg, The same girl, age 8, the scar almost gone


Cleft palate

Cleft palate is a condition in which the two plates of the
skull The skull is a bone A bone is a rigid tissue Tissue may refer to: Biology * Tissue (biology), an ensemble of similar cells that together carry out a specific function * ''Triphosa haesitata'', a species of geometer moth found in North A ...

skull
that form the
hard palate The hard palate is a thin horizontal bony plate made up of two bones of the facial skeleton The facial skeleton comprises the ''facial bones'' that may attach to build a portion of the skull The skull is a bone A bone is a Stiffness, ri ...
(roof of the mouth) are not completely joined. The
soft palate The soft palate (also known as the velum, palatal velum, or muscular palate) is, in mammal Mammals (from Latin Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was origin ...
is in these cases cleft as well. In most cases, cleft lip is also present. Palate cleft can occur as complete (soft and hard palate, possibly including a gap in the jaw) or incomplete (a 'hole' in the roof of the mouth, usually as a cleft soft palate). When cleft palate occurs, the
uvula The palatine uvula, usually referred to as simply the uvula, is a conic projection from the back edge of the middle of the soft palate The soft palate (also known as the velum, palatal velum, or muscular palate) is, in mammal Mammals (from ...
is usually split. It occurs due to the failure of fusion of the lateral palatine processes, the nasal septum, or the median palatine processes (formation of the
secondary palate The secondary palate is an anatomical structure that divides the nasal cavity The nasal cavity is a large, air-filled space above and behind the human nose, nose in the middle of the face. The nasal septum divides the cavity into two cavities, als ...
). The hole in the roof of the mouth caused by a cleft connects the mouth directly to the . Note: the next images show the roof of the mouth. The top shows the nose, the lips are colored pink. For clarity the images depict a toothless infant. File:Cleftpalate3.png, Incomplete cleft palate File:Cleftpalate1.png, Unilateral complete lip and palate File:Cleftpalate2.png, Bilateral complete lip and palate A result of an open connection between the
mouth In animal anatomy Anatomy (Greek ''anatomē'', 'dissection') is the branch of biology concerned with the study of the structure of organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is ...
and inside the nose is called
velopharyngeal insufficiency Velopharyngeal insufficiency is a disorder of structure that causes a failure of the velum (soft palate) to close against the posterior pharyngeal wall (back wall of the throat) during speech in order to close off the nose (nasal cavity) during o ...
(VPI). Because of the gap, air leaks into the nasal cavity resulting in a hypernasal voice
resonance Resonance describes the phenomenon of increased amplitude The amplitude of a Periodic function, periodic Variable (mathematics), variable is a measure of its change in a single Period (mathematics), period (such as frequency, time or Wavelen ...

resonance
and nasal emissions while talking. Secondary effects of VPI include speech errors (e.g., , substitutions, and omissions) and compensatory misarticulations and mispronunciations (e.g., s and posterior nasal
fricative Fricatives are consonants manner of articulation, produced by forcing air through a narrow channel made by placing two Place of articulation, articulators close together. These may be the lower lip against the upper teeth, in the case of ; the bac ...
s). Possible treatment options include
speech therapy Speech is human vocal communication Communication (from Latin ''communicare'', meaning "to share" or "to be in relation with") is "an apparent answer to the painful divisions between self and other, private and public, and inner thought and ...
, prosthetics, augmentation of the posterior pharyngeal wall, lengthening of the palate, and
surgical procedures Many surgical procedure Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical or dental specialty that uses operative manual and instrumental techniques on a per ...
. Submucous cleft palate can also occur, which is a cleft of the soft palate with a split
uvula The palatine uvula, usually referred to as simply the uvula, is a conic projection from the back edge of the middle of the soft palate The soft palate (also known as the velum, palatal velum, or muscular palate) is, in mammal Mammals (from ...

uvula
, a furrow along the midline of the soft palate, and a notch in the back margin of the hard palate. The diagnosis of submucous cleft palate often occurs late in children as a result of the nature of the cleft. While the muscles of the soft palate are not joined, the mucosal membranes covering the roof of the mouth appear relatively normal and intact.


Teeth

Tooth development can be delayed with increasing severity of CLP. Some of the dental problems affect the
primary teeth Deciduous teeth – commonly known as baby teeth, milk teeth, temporary teeth,Illustrated Dental Embryology, Histology, and Anatomy, Bath-Balogh and Fehrenbach, Elsevier, 2011, page 255 and primary teeth – are the first set of teeth in the grow ...
, but most of the problems arise after the permanent teeth erupts. Problems may include fused teeth, missing teeth, and extra teeth erupting behind normal teeth. Missing teeth or extra teeth are both normal occurrences. Typically, the lateral incisors are missing. The enamel (outermost layer of the tooth) is commonly found to be hypomineralized and hypoplastic, making the teeth more likely to decay. As CLP can make oral hygiene more difficult, there is an increased rate of cavities. In addition, abnormal positioning of individual teeth may affect occlusion, which can create an open bite or cross bite. This in turn can then affect the patient's speech.


Complications

Cleft may cause problems with feeding, ear disease, speech, socialization, and cognition. Due to lack of suction, an infant with a cleft may have trouble feeding. An infant with a cleft palate will have greater success feeding in a more upright position. Gravity will help prevent milk from coming through the baby's nose if he/she has cleft palate. Gravity feeding can be accomplished by using specialized equipment, such as the
Haberman Feeder to help the baby swallow the milk The Haberman Feeder (a registered trademark) is a speciality baby bottle, bottle named after its inventor Mandy Haberman for baby, babies with impaired sucking ability (for example due to cleft lip and palate or Mob ...

Haberman Feeder
. Another equipment commonly used for gravity feeding is a customized bottle with a combination of nipples and bottle inserts. A large hole, crosscut, or slit in the nipple, a protruding nipple and rhythmically squeezing the bottle insert can result in controllable flow to the infant without the stigma caused by specialized equipment. Individuals with cleft also face many middle ear infections which may eventually lead to hearing loss. The
Eustachian tube In anatomy Anatomy (Greek ''anatomē'', 'dissection') is the branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Mole ...
s and external ear canals may be angled or tortuous, leading to food or other contamination of a part of the body that is normally self-cleaning. Hearing is related to learning to speak. Babies with palatal clefts may have compromised hearing and therefore, if the baby cannot hear, it cannot try to mimic the sounds of speech. Thus, even before expressive language acquisition, the baby with the cleft palate is at risk for receptive language acquisition. Because the lips and palate are both used in pronunciation, individuals with cleft usually need the aid of a speech therapist. Tentative evidence has found that those with clefts perform less well at language.


Psychosocial issues

There is research dedicated to the
psychosocial development The psychosocial approach looks at individuals in the context of the combined influence that psychological factors and the surrounding social environment have on their physical and mental wellness and their ability to function. This approach is u ...
of individuals with cleft palate. A cleft palate/lip may impact an individual's
self-esteem Self-esteem is an individual's subjective evaluation of their own worth. Self-esteem encompasses beliefs about oneself (for example, "I am unloved", "I am worthy") as well as emotional states, such as triumph, despair, pride, and shame. Smith an ...
,
social skills A social skill is any competence facilitating interaction Interaction is a kind of action that occurs as two or more objects have an effect upon one another. The idea of a two-way effect is essential in the concept of interaction, as opposed t ...
and
behavior Behavior (American English American English (AmE, AE, AmEng, USEng, en-US), sometimes called United States English or U.S. English, is the set of variety (linguistics), varieties of the English language native to the United States. Cur ...
. Self-concept may be adversely affected by the presence of a cleft lip or cleft palate, particularly among girls. Negative outcomes can also be associated with the long durations of hospitalization. Psychological issues could extend not just to the individual with CLP but also to their families, particularly their mothers, that experience varying levels of depression and anxiety. Research has shown that during the early preschool years (ages 3–5), children with cleft lip or cleft palate tend to have a self-concept that is similar to their peers without a cleft. However, as they grow older and their social interactions increase, children with clefts tend to report more dissatisfaction with peer relationships and higher levels of
social anxiety Social anxiety is the anxiety and fear specifically linked to being in social settings (i.e., interacting with others). Some categories of disorders associated with social anxiety include anxiety disorder Anxiety disorders are a cluster of ment ...
. Experts conclude that this is probably due to the associated stigma of visible deformities and possible
speech impediment Speech is human vocal communication using language. Each language uses Phonetics, phonetic combinations of vowel and consonant sounds that form the sound of its words (that is, all English words sound different from all French words, even if the ...
s. Children who are judged as attractive tend to be perceived as more intelligent, exhibit more positive social behaviors, and are treated more positively than children with cleft lip or cleft palate. Children with clefts tend to report feelings of anger, sadness, fear, and alienation from their peers, but these children were similar to their peers in regard to "how well they liked themselves." The relationship between parental attitudes and a child's self-concept is crucial during the preschool years. It has been reported that elevated stress levels in mothers correlated with reduced social skills in their children. Strong parent support networks may help to prevent the development of negative self-concept in children with cleft palate. In the later preschool and early elementary years, the development of social skills is no longer only impacted by parental attitudes but is beginning to be shaped by their peers. A cleft lip or cleft palate may affect the behavior of preschoolers. Experts suggest that parents discuss with their children ways to handle negative social situations related to their cleft lip or cleft palate. A child who is entering school should learn the proper (and age-appropriate) terms related to the cleft. The ability to confidently explain the condition to others may limit feelings of awkwardness and embarrassment and reduce negative social experiences. As children reach adolescence, the period of time between age 13 and 19, the dynamics of the parent-child relationship change as peer groups are now the focus of attention. An adolescent with cleft lip or cleft palate will deal with the typical challenges faced by most of their peers including issues related to self-esteem, dating and social acceptance. Adolescents, however, view appearance as the most important characteristic, above intelligence and humor. This being the case, adolescents are susceptible to additional problems because they cannot hide their facial differences from their peers. Adolescent boys typically deal with issues relating to withdrawal, attention, thought, and internalizing problems, and may possibly develop anxiousness-depression and aggressive behaviors. Adolescent girls are more likely to develop problems relating to self-concept and appearance. Individuals with cleft lip or cleft palate often deal with threats to their
quality of life Quality of life (QOL) is defined by the World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations United Nations Specialized Agencies are autonomous organizations working with the United N ...

quality of life
for multiple reasons including unsuccessful social relationships, deviance in social appearance, and multiple surgeries.


Cause

Most clefts are polygenic and multifactorial in origin with many genetic and environmental factors contributing. Genetic factors cause clefts in 20% to 50% of the cases and the remaining clefts are attributable to either environmental factors (such as teratogens) or gene-environment interactions. The polygenic/multifactorial inheritance model predicts that most individuals will be born without clefts; however with a number of genetic or environmental factors, it can result in cleft formation. The development of the face is coordinated by complex morphogenetic events and rapid proliferative expansion, and is thus highly susceptible to environmental and genetic factors, rationalising the high incidence of facial malformations. During the first six to eight weeks of pregnancy, the shape of the embryo's head is formed. Five primitive tissue lobes grow: If these tissues fail to meet, a gap appears where the tissues should have joined (fused). This may happen in any single joining site, or simultaneously in several or all of them. The resulting birth defect reflects the locations and severity of individual fusion failures (e.g., from a small lip or palate fissure up to a completely malformed face). The upper lip is formed earlier than the palate, from the first three lobes named a to c above. Formation of the palate is the last step in joining the five embryonic facial lobes, and involves the back portions of the lobes b and c. These back portions are called palatal shelves, which grow towards each other until they fuse in the middle. This process is very vulnerable to multiple toxic substances, environmental pollutants, and nutritional imbalance. The biologic mechanisms of mutual recognition of the two cabinets, and the way they are glued together, are quite complex and obscure despite intensive scientific research. Orofacial clefts may be associated with a syndrome (syndromic) or may not be associated with a syndrome (nonsyndromic). Syndromic clefts are part of syndromes that are caused by a variety of factors such as environment and genetics or an unknown cause. Nonsyndromic clefts, which are not as common as syndromic clefts, also have a genetic cause.


Genetics

Genetic factors contributing to cleft lip and cleft palate formation have been identified for some syndromic cases. Many clefts run in families, even though in some cases there does not seem to be an identifiable syndrome present. A number of genes are involved including cleft lip and palate transmembrane protein 1 and
GAD1 Glutamate decarboxylase 1 (brain, 67kDa) (GAD67), also known as GAD1, is a human gene In biology, a gene (from ''genos'' "...Wilhelm Johannsen coined the word gene to describe the Mendelian_inheritance#History, Mendelian units of heredity.. ...
, One study found an association between mutations in the
HYAL2 Hyaluronidase-2 is a multifunctional protein, previously thought to only possess acid-active hyaluronan Hyaluronic acid (; abbreviated HA; conjugate base A conjugate acid, within the Brønsted–Lowry acid–base theory, is a chemical compo ...
gene and cleft lip and cleft palate formation.


Syndromes

* The
Van der Woude syndrome Van der Woude syndrome (VDWS) is a genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome In the fields of molecular biology and genetics Genetics is a branch of biology concern ...
is caused by a specific variation in the gene ''
IRF6 Interferon regulatory factor 6 also known as IRF6 is a protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions w ...
'' that increases the occurrence of these deformities threefold. Mutations in interferon regulatory factor 6 (IRF6) that cause cleft lip palate are also implicated in neural tube defects such as spina bifida. * Another syndrome, Siderius X-linked intellectual disability, is caused by mutations in the '' PHF8'' gene (); in addition to cleft lip or palate, symptoms include facial dysmorphism and mild mental retardation. In some cases, cleft palate is caused by syndromes that also cause other problems: * Stickler syndrome can cause cleft lip and palate, joint pain, and
myopia Near-sightedness, also known as short-sightedness and myopia, is an eye Eyes are organs of the visual system The visual system comprises the sensory organ (the eye) and parts of the central nervous system (the retina containing photor ...

myopia
. *
Loeys–Dietz syndrome Loeys–Dietz syndrome (LDS) is an autosomal dominant In genetics Genetics is a branch of biology concerned with the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) Though heredity had been observed f ...
can cause cleft palate or bifid uvula,
hypertelorism Hypertelorism is an abnormally increased distance between two organs or bodily parts, usually referring to an increased distance between the orbits (eyes), or orbital hypertelorism. In this condition the distance between the inner eye corners as w ...

hypertelorism
, and
aortic aneurysm An aortic aneurysm is an enlargement (dilatation) of the aorta to greater than 1.5 times normal size. They usually cause no symptoms except when ruptured. Occasionally, there may be abdominal, back, or leg pain. They are most commonly located ...

aortic aneurysm
. * Hardikar syndrome can cause cleft lip and palate,
Hydronephrosis Hydronephrosis describes hydrostatic dilation of the renal pelvis The renal pelvis or pelvis of the kidney is the funnel-like dilated part of the ureter in the kidney. In humans, the renal pelvis is the point where the two or three Renal calyx, majo ...

Hydronephrosis
,
Intestinal obstruction Bowel obstruction, also known as intestinal obstruction, is a mechanical or functional obstruction of the intestine The gastrointestinal tract, (GI tract, GIT, digestive tract, digestion tract, alimentary canal) is the tract from the mouth t ...
and other symptoms. * Cleft lip/palate may be present in many different chromosome disorders including
Patau syndrome Patau syndrome is a syndrome caused by a chromosomal abnormality, in which some or all of the cells of the body contain extra genetic material from chromosome 13. The extra genetic material disrupts normal development, causing multiple and comp ...
(trisomy 13). * Malpuech facial clefting syndrome * Hearing loss with craniofacial syndromes *
Popliteal pterygium syndrome Popliteal pterygium syndrome (PPS) is an inherited condition affecting the face The face is the front of an animal's head that features the eyes Eyes are organs An organ is a group of tissues with similar functions. Plant life and anima ...
*
Cornelia de Lange syndrome Cornelia de Lange syndrome (CdLS) is a genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome In the fields of molecular biology and genetics, a genome is all genetic information of ...
*
Treacher Collins syndrome Treacher Collins syndrome (TCS) is a genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome In the fields of molecular biology Molecular biology is the branch of biology ...
*
Pierre Robin syndrome Pierre Robin sequence (; abbreviated PRS) is a congenital defect observed in humans which is characterized by Craniofacial abnormality, facial abnormalities. The three main features are micrognathia (abnormally small mandible), which causes glossopt ...


Specific genes

Many genes associated with syndromic cases of cleft lip/palate (see above) have been identified to contribute to the incidence of isolated cases of cleft lip/palate. This includes in particular sequence variants in the genes ''
IRF6 Interferon regulatory factor 6 also known as IRF6 is a protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions w ...
'', ''
PVRL1 Poliovirus receptor-related 1 (PVRL1), also known as nectin-1 and CD111 (formerly herpesvirus entry mediator C, HVEC) is a human protein of the immunoglobulin superfamily (IgSF), also considered a member of the nectins. It is a membrane protein w ...
'' and ''
MSX1 Msh homeobox 1, also known as MSX1, is a protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Co ...

MSX1
''. The understanding of the genetic complexities involved in the
morphogenesis Morphogenesis (from the Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. Its population is a ...
of the midface, including molecular and cellular processes, has been greatly aided by research on animal models, including of the genes ''
BMP4 Bone morphogenetic protein 4 is a protein that in humans is encoded by ''BMP4'' gene. BMP4 is found on chromosome 14q22-q23 BMP4 is a member of the bone morphogenetic protein family which is part of the transforming growth factor-beta superfamily. ...
'', ''SHH'', ''SHOX2'', ''
FGF10 Fibroblast growth factor 10 is a protein Proteins are large s and s that comprise one or more long chains of . Proteins perform a vast array of functions within organisms, including , , , providing and , and from one location to another. P ...
'' and ''
MSX1 Msh homeobox 1, also known as MSX1, is a protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Co ...

MSX1
''.


Environmental factors

Environmental influences may also cause, or interact with genetics to produce, orofacial clefts. An example of the link between environmental factors and genetics comes from a research on mutations in the gene '' PHF8''. The research found that ''PHF8'' encodes for a
histone In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanisms ...
lysine demethylase, and is involved in epigenetic regulation. The catalytic activity of ''PHF8'' depends on molecular
oxygen Oxygen is the chemical element Image:Simple Periodic Table Chart-blocks.svg, 400px, Periodic table, The periodic table of the chemical elements In chemistry, an element is a pure substance consisting only of atoms that all have the same ...

oxygen
, a factor considered important from reports on increased incidence of cleft lip/palate in mice that have been exposed to hypoxia early during pregnancy. Cleft lip and other
congenital abnormalities A birth defect, also known as a congenital disorder, is a condition present at birth Birth is the act or process of bearing or bringing forth offspring, also referred to in technical contexts as parturition. In mammals, the process is initiat ...
have also been linked to maternal hypoxia caused by , with the estimated attributable fraction of orofacial clefts due to smoking in early pregnancy being 6.1%. Orofacial clefts occur very early in pregnancy and so smoking cessation right after recognition of pregnancy is unlikely to reduce the exposure during the critical time period. Maternal alcohol use has also been linked to cleft lip and palate due to the effects on the cranial
neural crest Neural crest cells are a temporary group of cells unique to vertebrate Vertebrates () comprise all species of animal Animals (also called Metazoa) are multicellular eukaryotic organisms that form the Kingdom (biology), biological kingd ...

neural crest
cells. The degree of the effect, however, is unknown and requires further research. Some forms of maternal
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not ...

hypertension
treatment have been linked to cleft lip and palate. Other environmental factors that have been studied include seasonal causes (such as pesticide exposure); maternal diet and vitamin intake;
retinoid The retinoids are a class of chemical compounds A chemical compound is a chemical substance A chemical substance is a form of matter In classical physics and general chemistry, matter is any substance that has mass and takes up space ...
s (members of the vitamin A family);
anticonvulsant Anticonvulsants (also commonly known as antiepileptic drugs or as antiseizure drugs) are a diverse group of pharmacological Pharmacology is a branch of medicine Medicine is the Art (skill), art, science, and Praxis (process) , practice of ...
drugs; nitrate compounds; organic solvents; parental exposure to lead; alcohol; cigarette use; and a number of other psychoactive drugs (e.g.
cocaine Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a tropane alkaloid and stimulant drug obtained primarily from the leaves of two coca species native to South America, ''Erythroxylum coca'' and ''Erythroxylu ...

cocaine
,
crack cocaine Crack cocaine, commonly known simply as crack, and also known as rock, is a free base Free base (freebase, free-base) is the conjugate base A conjugate acid, within the Brønsted–Lowry acid–base theory The Brønsted–Lowry theor ...
,
heroin Heroin, also known as diacetylmorphine and diamorphine among other names, is an opioid Opioids are substances that act on opioid receptor Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. T ...

heroin
). Current research continues to investigate the extent to which
folic acid Folate, also known as vitamin B9 and folacin, is one of the B vitamins B vitamins are a class of water-soluble vitamin A vitamin is an organic molecule , CH4; is among the simplest organic compounds. In chemistry, organic compounds ar ...

folic acid
can reduce the incidence of clefting. Folic acid alone or in combination with vitamins and minerals prevents neural tube defects but does not have a clear effect on cleft lip palate incidence. The mechanism behind beneficial folate supplementation is due to folate playing a pivotal role in DNA synthesis and methylation and contributes to both development and gene expression.


Diagnosis

Traditionally, the diagnosis is made at the time of birth by physical examination. Recent advances in
prenatal diagnosis Prenatal development () includes the development of the embryo and of the foetus during a viviparous animal's gestationGestation is the period of development during the carrying of an embryo An embryo is the early stage of development of a ...
have allowed
obstetrician Obstetrics is the field of study concentrated on pregnancy Pregnancy, also known as gestation, is the time during which one or more offspring In biology, offspring are the young creation of living organisms, produced either by a Asex ...
s to diagnose facial clefts
in utero The uterus (from Latin "uterus", plural ''uteri'') or womb () is a major female hormone-responsive sex organ, secondary sex organ of the reproductive system in humans and most other mammals. Things occurring in the uterus are described with the ...

in utero
with
ultrasonography Ultrasound is sound wave In physics Physics (from grc, φυσική (ἐπιστήμη), physikḗ (epistḗmē), knowledge of nature, from ''phýsis'' 'nature'), , is the natural science that studies matter, its Motion (phys ...
. Clefts can also affect other parts of the face, such as the eyes, ears, nose, cheeks, and forehead. In 1976, Paul Tessier described fifteen lines of cleft. Most of these
craniofacial cleftA facial cleft is an opening or gap in the face, or a malformation of a part of the face. Facial clefts is a collective term for all sorts of clefts. All structures like bone, soft tissue, skin etc. can be affected. Facial clefts are extremely rare c ...
s are even rarer and are frequently described as Tessier clefts using the numerical locator devised by Tessier.


Classification

Cleft lip and cleft palate is an "umbrella term" for a collection of orofacial clefts. It includes clefting of the upper lip, the maxillary alveolus (dental arch), and the hard or
soft palate The soft palate (also known as the velum, palatal velum, or muscular palate) is, in mammal Mammals (from Latin Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was origin ...
, in various combinations. Proposed anatomic combinations include: *cleft lip *cleft lip and alveolus *cleft lip, alveolus, and palate *cleft lip and palate (with an intact alveolus) *cleft palate


Prenatal diagnosis

Cleft lip with or without palate is classified as the most common congenital birth defect. It has been noted that the prevalence of orofacial clefts varies by race. The highest number of cases have been recorded among Asians and Native Americans, followed by Europeans, Hispanics and African-Americans. The critical period for cleft development ranges from the 4th to the 12th week of intrauterine life. Clefts of the primary palate develop between the 4th and 7th weeks of intrauterine life, while clefts of the secondary palate develop between the 8th and 12th embryonic weeks. Accurate evaluation of craniofacial malformations is usually possible with the ultrasound scan performed during pregnancy. This is however not a routine procedure according to the American Institute of Ultrasound in Medicine. The accuracy of ultrasonography for prenatal diagnosis of cleft lip +/- palate is dependent on the experience of the sonologist, maternal body type, foetal position, the amount of amniotic fluid and the type of cleft. Prenatal diagnosis enables appropriate and timely education and discussion with parents by the cleft team. This helps improve the quality of treatment received by the child and improves quality of life. An accurate prenatal diagnosis of the CLP anomaly is critical for establishing long-term treatment planning, prediction of treatment outcome, and discussion and education of the parent. Although there is no intrauterine treatment for CLP, both mother and child benefit from early diagnosis and education. A multidisciplinary team approach is now accepted as the standard of care in dealing with CLP patients. The time period immediately after the diagnosis and the 1st year after the birth is most challenging for parents. A systematically planned treatment plan and support system will help assist parents. The ultimate aim is to help educate parents and create awareness so as to improve care provided for the child.


Treatment

Cleft lip and palate is very treatable; however, the kind of treatment depends on the type and severity of the cleft. Most children with a form of clefting are monitored by a ''cleft palate team'' or ''craniofacial team'' through young adulthood. Care can be lifelong and are looked after by craniofacial cleft teams often consist of: cleft surgeons,
orthodontists Orthodontics is a specialty of dentistry that deals with the diagnosis, prevention, and correction of malpositioned teeth and jaws, and misaligned bite patterns. It can also focus on modifying facial growth, known as dentofacial orthopedics. Abnor ...
, speech and language therapists, restorative dentists,
Psychologist A psychologist is a professional who practices psychology and studies normal and abnormal mental states, perceptual, cognitive, emotional, and social processes and behavior by experimenting with, and observing, interpreting, and recording how ...
s, ENT surgeons and audio-logical physicians. Treatment procedures can vary between craniofacial teams. For example, some teams wait on jaw correction until the child is aged 10 to 12 (argument: growth is less influential as
deciduous teeth Deciduous teeth or primary teeth, also informally known as baby teeth, milk teeth, or temporary teeth,Illustrated Dental Embryology, Histology, and Anatomy, Bath-Balogh and Fehrenbach, Elsevier, 2011, page 255 are the first set of teeth A ...
are replaced by
permanent teeth Permanent teeth or adult teeth are the second set of teeth A tooth (plural teeth) is a hard, calcification, calcified structure found in the jaws (or mouths) of many vertebrates and used to Mastication, break down food. Some animals, particular ...
, thus saving the child from repeated corrective surgeries), while other teams correct the jaw earlier (argument: less speech therapy is needed than at a later age when speech therapy becomes harder). Within teams, treatment can differ between individual cases depending on the type and severity of the cleft.


Cleft lip

Within the first 2–3 months after birth, surgery is performed to close the cleft lip. While surgery to repair a cleft lip can be performed soon after birth, often the preferred age is at approximately 10 weeks of age, following the " rule of 10s" coined by surgeons Wilhelmmesen and Musgrave in 1969 (the child is at least 10 weeks of age; weighs at least 10 pounds, and has at least 10g hemoglobin). If the cleft is bilateral and extensive, two surgeries may be required to close the cleft, one side first, and the second side a few weeks later. The most common procedure to repair a cleft lip is the ''Millard procedure'' pioneered by Ralph Millard. Millard performed the first procedure at a
Mobile Army Surgical Hospital General information U.S Army MASH Units or Mobile Army Surgical Hospitals were conceptualized in 1946 as revolutionized units of ASG Units which were “Auxiliary Surgical Hospitals” made during World War II became obsolete. MASH units had ...
(MASH) unit in Korea. Often an incomplete cleft lip requires the same surgery as complete cleft. This is done for two reasons. Firstly the group of
muscle Skeletal muscles (commonly referred to as muscles) are organs An organ is a group of tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. A given organ's tissues can be broadly cat ...

muscle
s required to purse the lips run through the upper lip. To restore the complete group a full incision must be made. Secondly, to create a less obvious scar the surgeon tries to line up the scar with the natural lines in the upper lip (such as the edges of the
philtrum The philtrum ( la, philtrum from Ancient Greek Ancient Greek includes the forms of the Greek language used in ancient Greece and the classical antiquity, ancient world from around 1500 BC to 300 BC. It is often roughly divided into the f ...

philtrum
) and tuck away stitches as far up the nose as possible. Incomplete cleft gives the surgeon more tissue to work with, creating a more supple and natural-looking upper lip. File:Millardrepair1.svg, The blue lines indicate incisions. File:Millardrepair2.svg, Movement of the flaps; flap A is moved between B and C. C is rotated slightly while B is pushed down. File:Baby_girl_with_cleft_palate,_smiling.jpg , Pre-operation File:17161036 POSTOPT3.jpg, Post-operation, the lip is swollen from surgery and will look more natural within weeks. See photos in the section above.


Pre-surgical devices

In some cases of a severe bi-lateral complete cleft, the premaxillary segment will be protruded far outside the mouth. prior to surgery can improve long-term nasal symmetry where there is complete unilateral cleft lip–cleft palate, compared to correction by surgery alone, according to a retrospective
cohort study A cohort study is a particular form of longitudinal study A longitudinal study (or longitudinal survey, or panel study) is a research design Research design refers to the overall strategy utilized to carry out research Research is "crea ...
. In this study, significant improvements in nasal symmetry were observed in multiple areas including measurements of the projected length of the nasal ala (lateral surface of the external nose), position of the superoinferior alar groove, position of the mediolateral nasal dome, and nasal bridge deviation. "The nasal ala projection length demonstrated an average ratio of 93.0 percent in the surgery-alone group and 96.5 percent in the nasoalveolar molding group," this study concluded. A
systematic review Systematic reviews are a type of Literature review, review that uses repeatable analytical methods to collect secondary data and analyse it. Systematic reviews are a type of evidence synthesis which formulate research questions that are broad or ...
found in conclusion that nasoalveolar molding had a positive effect on the primary surgery of cleft lip/or palate treatment and aesthetics.


Cleft palate

Often a cleft palate is temporarily covered by a
palatal obturator{{no footnotes, date=February 2017 The Latham Device Post Latham Nasal Alveolar Molding Device file:Post Nasal Alveolar Molding.jpg, Post Insertion A palatal obturator is a prosthesis that totally occludes an opening such as an oronasal fistula ( ...
(a prosthetic device made to fit the roof of the mouth covering the gap). This device re-positions displaced alveolar segments and helps reduce the cleft lip separation. The obturator will improve speech as there's now proper airflow and improve feeding and breathing as the gap in the hard and soft palate is closed over so cannot affect it. Cleft palate can also be corrected by
surgery Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical or dental specialty that uses operative manual and instrumental techniques on a person to investigate or t ...
, usually performed between 6 and 12 months. Approximately 20–25% only require one palatal surgery to achieve a competent velopharyngeal valve capable of producing normal, non-
hypernasal speech Hypernasal speech is a disorder that causes abnormal resonance in a human's voice due to increased airflow through the nose during speech. It is caused by an open nasal cavity resulting from an incomplete closure of the soft palate and/or velophary ...
. However, combinations of surgical methods and repeated surgeries are often necessary as the child grows. One of the new innovations of cleft lip and cleft palate repair is the Latham appliance. The Latham is surgically inserted by use of pins during the child's 4th or 5th month. After it is in place, the doctor, or parents, turn a screw daily to bring the cleft together to assist with future lip or palate repair. If the cleft extends into the maxillary alveolar ridge, the gap is usually corrected by filling the gap with bone tissue. The bone tissue can be acquired from the individual's own chin, rib or hip. At age 1–7 years the child is regularly reviewed by the cleft team. Age 7–12 years, for the children born with alveolar clefts, they may need to have a secondary alveolar bone graft. This is where autogenous cancellous bone from a donor site (often the pelvic bone) is transplanted into the alveolar cleft region. This transplant of bone will close the osseous cleft of the alveolus, close any oro-nasal fistulae and will become integrated with the maxillary bone. It provides bone for teeth to erupt into and to allow implants to be placed as a possible future treatment option. The procedure should be carried out before the upper canine has erupted. Ideally the root of the canine should be one to two-thirds formed and that there is a space available to place the bone graft. Radiography, Radio-graphs are taken to determine the quantity of missing bone in the cleft area.


Other surgeries

Orthognathic surgery – surgical cutting of bone to realign the upper jaw (osteotomy). The bone is cut then re-positioned and held together by wires or rigid fixation plates to ensure there's no anterior-posterior discrepancy, also to reduce scarring as it reduces growth. Single piece or multi-piece osteotomy exist. Single piece osteotomy is carried out where there is sufficient alveolar continuity achieved from a successful bone graft. Multi piece osteotomy is performed when there is a notable residual alveolar defect with a dental gap and oronasal fistula (communication between the oral and nasal cavities). The goal of both single and multi piece osteotomy is to displace the maxilla forward to obtain adequate occlusion as well to provide better support for upper lip and the nose and to close any fistulae. Distraction osteogenesis – bone lengthening by gradual distraction. This involves cutting bone and moving ends apart incrementally to allow new bone to form in the gap. This consists of several phases. After attachment of the distracting device and the bone cuts, there is a latency phase of 3–7 days when a Callus (cell biology), callus forms. In the activation phase distraction of the callus induces bony ingrowth which can last up to 15 days depending on the required distraction. Once the required bone length is reached, the distraction device is left to remain in situ as it acts as a rigid skeletal fixation device until the new bone has matured (known as the consolidation period).


Speech

Velopharyngeal insufficiency (VPI) can occur as a result of an unrepaired or repaired cleft lip and palate. VPI is the inability of the soft palate to close tightly against the back of the throat during speech, resulting in incomplete velopharyngeal closure. In turn, this results in speech abnormalities. Velopharyngeal closure is necessary during speech because it forms a seal between the nose and mouth, allowing the production of normal speech sounds. VPI can cause hypernasality (excessive nasal resonance), hyponasality (reduced nasal resonance), or a mixed nasal resonance, which is when hypernasality and hyponasality occur simultaneously. In addition, CLP may cause abnormal positioning of individual teeth, which can in turn affect the patient's ability to make certain sounds when speaking such as the "f" or "v" sound and can also result in a lisp. The changes in speech may also be a manifestation on CLP's effects on the patient's occlusion.


Hearing

Children with cleft palate have a very high risk of developing a middle ear infection, specifically otitis media. This is due to the immature development of the different bones and muscles in the ear. Otitis media is caused by the obstruction of the
Eustachian tube In anatomy Anatomy (Greek ''anatomē'', 'dissection') is the branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Mole ...
, negative middle ear pressure and fluid build-up in the normally air-filled space of the middle ear. This is associated with hearing impairment or loss. The insertion of a ventilation tube into the eardrum is a surgical treatment option commonly used to improve hearing in children with otitis media. In addition, breast milk has been proven to decrease the incidence of otitis media in infants with clefts.


Feeding

There are different options on how to feed a baby with cleft lip or cleft palate which include: Breastfeeding, breast-feeding, bottle feeding, spoon feeding and syringe feeding. Although breast-feeding is challenging, it improves weight-gain compared to spoon-feeding. Nasal regurgitation is common due to the open space between the oral cavity and the nasal cavity. Bottle feeding can help (with squeezable bottles being easier to use than rigid bottles). In addition, maxillary plates can be added to aid in feeding. Whatever feeding method is established, it is important to keep the baby's weight gain and hydration monitored. Infants with cleft lip or palate may require supplemental feeds for adequate growth and nutrition. Breast feeding position as suggested by specialists can also improve success rate.


Breast-feeding

Babies with cleft lip are more likely to breastfeed successfully than those with cleft palate and cleft lip and palate. Larger clefts of the soft or hard palate may not be able to generate suction as the oral cavity cannot be separated from the nasal cavity when feeding which leads to fatigue, prolonged feeding time, impaired growth and nutrition. Changes in swallowing mechanics may result in coughing, choking, gagging and nasal regurgitation. Even after cleft repair, the problem may still persist as significant motor learning of swallowing and sucking was absent for many months before repair. These difficulties in feeding may result in secondary problems such as poor weight gain, excessive energy expenditure during feeding, lengthy feeding times, discomfort during feeding, and stressful feeding interactions between the infant and the mother. A potential source of discomfort for the baby during or after feeding is bloating or frequent "spit up" which is due to the excessive air intake through the nose and mouth in the open cleft. Babies with cleft lip and or palate should be evaluated individually taking into account the size and location of the cleft and the mother's previous experience with breastfeeding. Another option is feeding breast milk via bottle or syringe. Since babies with clip lip and cleft palate generate less section when breastfeeding, their nutrition, hydration and weight gain may be affected. This may result in the need for supplemental feeds. Modifying the position of holding the baby may increase the effectiveness and efficiency of breastfeeding.


Alternative Feeding Methods

Preoperative feeding – using a squeezable bottle instead of a rigid bottle can allow a higher volume of food intake and less effort to extract food. Using a syringe is practical, easy to perform and allows greater administered volume of food. It also means there will be weight gain and less time spent feeding. Post-operative feeding (isolated lip repair, or lip repair associated or not with palatoplasty) - post palatoplasty, some studies believe that inappropriate negative pressure on the suture line may affect results. Babies can be fed by a nasogastric tube instead. Studies suggest babies required less analgesics and shorter hospital stay with nasogastric feeding post-surgery. With bottle-feeding, there was higher feeding rejection and pain and required more frequent and prolonged feeding times.


Treatment schedule

Each person's treatment schedule is individualized. The table below shows a common sample treatment schedule. The colored squares indicate the average timeframe in which the indicated procedure occurs. In some cases, this is usually one procedure, for example lip repair. In other cases, it is an ongoing therapy, for example speech therapy. In most cases of cleft lip and palate that involve the alveolar bone, patients will need a treatment plan including the prevention of cavities, orthodontics, alveolar bone grafting, and possibly jaw surgery.


Cleft team

People with CLP present with a multiplicity of problems. Therefore, effective management of CLP involves a wide range of specialists. The current model for delivery of this care is the multidisciplinary cleft team. This is a group of individuals from different specialist backgrounds who work closely together to provide patients with comprehensive care from birth through adolescence. This system of delivery of care enables the individuals within the team to function in an interdisciplinary way, so that all aspects of care for CLP patients can be provided in the best way possible.


Outcomes assessment

Measuring the outcomes of CLP treatment has been laden with difficulty due to the complexity and longitudinal nature of cleft care, which spans birth through young adulthood. Prior attempts to study the effectiveness of specific interventions or overall treatment protocols have been hindered by a lack of data standards for outcomes assessment in cleft care. The International Consortium for Health Outcome Measurement (ICHOM) has proposed the Standard Set of Outcome Measures for Cleft Lip and Palate. The ICHOM Standard Set includes measures for many of the important outcome domains in cleft care (hearing, breathing, eating/drinking, speech, oral health, appearance and psychosocial well-being). It includes clinician-reported, patient-reported, and family-reported outcome measures.


Epidemiology

Cleft lip and palate occurs in about 1 to 2 per 1000 births in the
developed world A developed country (or industrialized country, high-income country, more economically developed country (MEDC), advanced country) is a sovereign state that has a high quality of life, developed economy and advanced technological infrastructu ...
. Rates for cleft lip with or without cleft palate and cleft palate alone varies within different Ethnicity, ethnic groups. According to CDC, the prevalence of cleft palate in the United States is 6.35/10000 births and the prevalence of cleft lip with or without cleft palate is 10.63/10000 births. The highest prevalence rate (mathematics), rates for cleft lip, either with or without cleft palate are reported for Native Americans and Asians. Ethnic groups of Africa, Africans have the lowest prevalence rates. * Native Americans: 3.74/1000 *Japanese: 0.82/1000 to 3.36/1000 *Han Chinese, Chinese: 1.45/1000 to 4.04/1000 *Caucasian race, Caucasians: 1.43/1000 to 1.86/1000 *Latin Americans: 1.04/1000 *Africans: 0.18/1000 to 1.67/1000 Cleft lip and cleft palate caused about 3,800 deaths globally in 2017, down from 14,600 deaths in 1990. Prevalence of "cleft
uvula The palatine uvula, usually referred to as simply the uvula, is a conic projection from the back edge of the middle of the soft palate The soft palate (also known as the velum, palatal velum, or muscular palate) is, in mammal Mammals (from ...

uvula
" has varied from 0.02% to 18.8% with the highest numbers found among Chippewa and Navajo people, Navajo and the lowest generally in Africans.


Society and culture


Abortion controversy

In some countries, cleft lip or palate deformities are considered reasons (either generally tolerated or officially sanctioned) to perform an abortion beyond the legal fetal age limit, even though the fetus is not in jeopardy of life or limb. Some human rights activists contend that this practice of what they refer to as "cosmetic murder" amounts to eugenics.


Works of fiction

The eponymous hero of J.M. Coetzee's 1983 novel ''Life & Times of Michael K'' has a cleft lip that is never corrected. In the 1920 novel ''Growth of the Soil,'' by Norwegian writer Knut Hamsun, Inger (wife of the main character) has an uncorrected cleft lip which puts heavy limitations on her life, even causing her to kill her own child, who is also born with a cleft lip. The protagonist of the 1924 novel ''Precious Bane'', by English writer Mary Webb, is a young woman living in 19th-century rural Shropshire who eventually comes to feel that her deformity is the source of her spiritual strength. The book was later adapted for television by both the BBC and ORTF in France. In the 1976 Patricia A. McKillip novel The Night Gift, one of the high-school aged protagonists is shy because she has a cleft lip, but learns to have more confidence in herself. In the first edition of ''Harry Potter and the Chamber of Secrets'', one of the people Gilderoy Lockhart stole credit from was a witch with a harelip who banished the Bandon Banshee. In later editions, this was changed to a witch with a hairy chin. In chapter 24 of Mark Twain's The Adventures of Huckleberry Finn, Huck Finn meets the three Wilks sisters, Mary Jane, Susan, and Joanna. Joanna is described as, "the one who gives herself to good works and has a hare-lip." As a form of offensive synecdoche, Huck Finn refers to Joanna as "the hare-lip" rather than by her name. In ''Inheritance (Paolini novel), Inheritance'', the final title of Christopher Paolini's ''Inheritance Cycle'', the main character Eragon heals a newborn girl with this condition in a display of complicated healing magic. It is stated that those within Eragon's society born with this condition are often not allowed to live as they face a very hard life. Cleft lip and cleft palate are often portrayed negatively in popular culture. Examples include Oddjob, the secondary villain of the James Bond novel Goldfinger (novel), ''Goldfinger'' by Ian Fleming (Goldfinger (film), the film adaptation does not mention this but leaves it implied) and serial killer Francis Dolarhyde in the novel Red Dragon (novel), ''Red Dragon'' and its screen adaptations, ''Manhunter (film), Manhunter'', ''Red Dragon (2002 film), Red Dragon'', and ''Hannibal (TV series), Hannibal''. The portrayal of enemy characters with cleft lips and cleft palates, dubbed mutants, in the 2019 video game ''Rage 2'' left Chris Plante of ''Polygon (website), Polygon'' wondering if the condition would ever be portrayed positively.


Notable cases


Other animals

Cleft lips and palates are occasionally seen in cattle and dogs, and rarely in goats, sheep, cats, horses, pandas and ferrets. Most commonly, the defect involves the lip, rhinarium, and premaxilla. Clefts of the hard and soft palate are sometimes seen with a cleft lip. The cause is usually hereditary. Brachycephalic syndrome, Brachycephalic dogs such as Boxer (dog), Boxers and Boston Terriers are most commonly affected. An inherited disorder with incomplete penetrance has also been suggested in Shih tzus, Swiss Sheepdogs, Bulldogs, and Pointer (dog breed), Pointers. In horses, it is a rare condition usually involving the caudal soft palate. In Charolais cattle, clefts are seen in combination with arthrogryposis, which is inherited as an Recessive allele, autosomal recessive trait. It is also inherited as an autosomal recessive trait in Texel (sheep), Texel sheep. Other contributing factors may include maternal nutritional deficiencies, exposure ''in utero'' to viral infections, trauma, drugs, or chemicals, or ingestion of toxins by the mother, such as certain lupines by cattle during the second or third month of gestation. The use of corticosteroids during pregnancy in dogs and the ingestion of ''Veratrum californicum'' by pregnant sheep have also been associated with cleft formation. Difficulty with nursing is the most common problem associated with clefts, but aspiration pneumonia, Regurgitation (digestion), regurgitation, and malnutrition are often seen with cleft palate and is a common cause of death. Providing nutrition through a feeding tube is often necessary, but corrective surgery in dogs can be done by the age of twelve weeks. For cleft palate, there is a high rate of surgical failure resulting in repeated surgeries. Surgical techniques for cleft palate in dogs include prosthesis, mucosal flaps, and microvascular free flaps. Affected animals should not be bred due to the hereditary nature of this condition. File:Cleft lip in boxer.JPG, Cleft lip in a Boxer File:Cleft lip in boxer 2.JPG, Cleft lip in a Boxer with premaxillary involvement File:Cleft lip adult dog.JPG, Same dog as picture on left, one year later


See also

* Smile Pinki * Palatal obturator * Vomer flap surgery * Cleft lip and palate organisations * Face and neck development of the embryo


References

Notes Further reading
FIGURE 1 , Development of the lip and palate
an

in *


External links

* {{DEFAULTSORT:Cleft Lip And Palate Congenital oral disorders Facial features Dog health Lip disorders Wikipedia medicine articles ready to translate