Materiały źródłowe

• #1 Cleft lip and cleft palate – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/cleft-palate/symptoms-causes/syc-20370985

  A cleft lip is an opening or split in the upper lip that doesn’t close fully when an unborn baby is developing in the womb. […] A cleft palate is an opening or split in the roof of the mouth that occurs when the tissue doesn’t close fully during development in the womb before birth. […] Cleft lip and cleft palate occur when an unborn baby’s face and mouth are developing and the upper lip and palate don’t close fully. […] Cleft lip and cleft palate are among the most common birth defects. These birth defects can occur on their own or together. Sometimes a syndrome may cause these birth defects. But the cause is often not known. […] Cleft lip and cleft palate occur when tissues in the baby’s face and mouth don’t come together properly before birth. Usually, the tissues that make up the lip and palate come together in the first few weeks of pregnancy. But in babies with cleft lip and cleft palate, they never come together or only come together partway, leaving an opening.

• #1 Cleft lip and cleft palate: Causes, treatment, and speech

  https://www.medicalnewstoday.com/articles/164660

  Cleft lip and cleft palate are structural abnormalities that form during fetal development. […] Doctors do not know exactly why a cleft occurs. As a baby develops in the womb, the structures that form the lip and roof of the mouth join. In some cases, this does not happen correctly, resulting in a cleft. […] Doctors do not know precisely why some children are born with a cleft, but it happens when structures in the mouth do not form as they should while the skull is developing. […] The lip forms between the fourth and seventh weeks of pregnancy. As the fetus develops, tissue and cells from either side join at the center of the face to form the lip and the palate. If they do not fuse, a cleft can occur. […] The roof of the mouth, or the palate, develops between the sixth and ninth weeks of pregnancy. As with the lip, a gap can form if the two sides do not join. In some babies, the gap affects only part of the palate. In others, it may affect the whole palate.

• #1 Cleft lip and palate | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/cleft-lip-and-palate?lang=us

  Cleft lip and palate is one of the commonest neonatal facial anomalies. In ~80% of cases, the two features tend to occur together. […] The condition results during the 4th to 6th weeks of gestation from a failure of fusion of one or both of the medial nasal prominences. These initially occur as paired medial nasal processes and failure of fusion with each other or with the maxillary processes will result in cleft lip with or without a cleft palate. […] In a sizable proportion, it is sporadic, although various inheritance patterns have been described.

• #1 Cleft lip and cleft palate – Wikipedia

  https://en.wikipedia.org/wiki/Cleft_lip_and_cleft_palate

  Cleft lip and palate are the result of tissues of the face not joining properly during development. As such, they are a type of birth defect. The cause is unknown in most cases. Risk factors include smoking during pregnancy, diabetes, obesity, an older mother, and certain medications (such as some used to treat seizures). […] 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 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.

• #1 Cleft Lip & Palate Association

  https://www.clapa.com/what-is-cleft-lip-palate/what-causes-a-cleft/

  There have been a number of environmental factors linked to a higher chance of a baby developing a cleft. […] It is important to note that these are just factors, and that the causes of cleft are usually much more complicated than what someone did or didn’t do while pregnant. […] While some conditions can point to a single genetic factor as a cause, there have been a number of different genes identified as increasing the risk of having a child with a cleft. […] Sometimes a cleft is caused by part of a ‘syndrome’, which is when lots of different symptoms happen together. […] Estimates can vary widely, but based on UK statistics, around 15-30% of clefts happen as part of a syndrome or condition. […] The causes of cleft lip and palate are much more complicated and vary greatly from case to case, so even if both parents have a cleft it can be very difficult to accurately predict how, if at all, their children will be affected.

• #1 Cleft Lip and Palate Diagnosis, Causes, Treatment | National Institute of Dental and Craniofacial Research

  https://www.nidcr.nih.gov/health-info/cleft-lip-palate

  Cleft lip with or without cleft palate is among the most common of birth defects. […] The most recent research suggests that cleft lip or palate is caused by: […] A gene defect inherited from one or both parents prevents the lips and mouth from joining during development in the womb. […] A genetic syndrome is a disease that has more than one symptom or defect. It can be caused by a single gene or many genes. Cleft lip or palate are found in more than 400 syndromes, including Waardenburg, Pierre Robin, and Down syndromes. Approximately 30 percent of cleft defects are associated with a genetic syndrome. […] A mothers poor health in early pregnancy, or if she drinks alcohol, smokes cigarettes, or takes certain anti-epileptic medications may increase the risk for cleft lip or palate.

• #1 Cleft of lip and palate: A review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7491837/

  Cleft of lip and palate are most common serial congenital anomalies to affect the orofacial region. It can occur isolated or together in various combination and/or along with other congenital deformities particularly congenital heart diseases. Clefts arises during the fourth developmental stage. Exactly where they appears is determined by locations at which fusion of various facial processes failed to occur, this in turn is influenced by the time in embryologic life when some interference with development occurred. In the developed world, most scientists believe that clefts occur due to a combination of genetic and environmental factors (e.g., maternal illness, drugs, malnutrition). Overall incidence of cleft lip and palate is approximately 1 in 600 to 800 live births (1.42 in 1000) and isolated cleft palate occurs approximately in 1 in 2000 live births. The potential problems of the condition include social handicaps such as impaired suckling and resultant failure to thrive, speech impediment, deafness, malocclusion, gross facial deformity and severe psychological problems. The etiology of cleft lip and palate is complex and thought to involve genetic influences with variable interactions from environmental factors. The etiological factors of cleft lip and palate can be grouped as under: Non-genetic: this includes various environmental (teratogenic) risk factors which may cause CL/P. Genetic cause includes: Syndromic: Here cleft is associated with other malformation. Usually it is due to a single gene (monogenic or Mendelian) disorder. Non-syndromic: Here the cleft is mostly an isolated feature and occurs in the vast majority of individuals having a cleft lip or palate (up to 70% cases). In this form, a cleft is neither a recognized pattern of malformation nor a known cause for the disorder can be identified. Various environmental factors includes: Smoking: The relationship between maternal smoking and CLP is not strong, but it is significant. Several studies have consistently yielded a relative risk of about 1.31.5. Alcohol use: Heavy maternal drinking, apart from causing fetal alcohol syndrome, also increases the risk of CLP. Others: Environmental factor includes maternal diseases, stress during pregnancy chemical exposure. Genetic factor: Various epidemiological observation have laid the foundation of role of genetics in etiology of cleft lip and palate. Many studies have shown that monozygotic twins (60%) have considerable higher concordance rate than dizygotic twins and siblings (5-10%). Syndromic form of cleft lip and palate: It accounts for more than 400 known syndromes and many of them follows classic Mendelian inheritance pattern. Non-syndromic form of cleft lip and palate: It accounts for 70% of CL/P cases and 50% of all CPO cases.

• #1 Pediatric Cleft Lip and Palate: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/995535-overview

  In general, any factor that could prevent the processes from reaching each otherfor instance, by slowing down migration or multiplication of neural crest cells, by stopping tissue growth and development for a time, or by killing some cells that are already in that locationwould cause a cleft to persist. […] There has been considerable interest in identifying genes that contribute to the etiology of orofacial clefting. […] The first candidate gene was transforming growth factor- (TGFA), which showed an association with nonsyndromic CLP in a White population. […] Other candidate genes that were described as being associated with nonsyndromic CLP included D4S192, RARA, MTHFR, RFC1, GABRB3, PVRL1, and IRF6. […] The identification of factors that contribute to the etiology of nonsyndromic CL/P is important for prevention, treatment planning, and education.

• #1 Causes of Cleft Lip & Palate – Department of Pediatrics

  https://med.virginia.edu/pediatrics/clinical-and-patient-services/patient-tutorials/cleft-lip-palate/causes-of-cleft-lip-palate/

  In general, the risks of giving birth to a child with a cleft palate are highest when both parents have clefts themselves. If only one parent has a cleft palate, the risk of having a baby with a cleft palate is 1 in 20 (5%). If a set of parents, neither of whom have a cleft, gives birth to a child with a cleft, the chances of them giving birth to a second child with a cleft palate is between 2 to 4 percent. […] Women older than 35 must be counseled regarding the maternal age risk factors because older women are more likely to give birth to a child with a birth defect. Also, families with a history of cleft palates should seek genetic counseling to determine their relative risks for giving birth to a child with a cleft palate.

• #1 Causes of Cleft Lip and Cleft Palate | Stanford Health Care

  https://stanfordhealthcare.org/medical-conditions/mouth-and-jaw/cleft-lip-cleft-palate/causes.html

  The exact cause of cleft lip and cleft palate is not completely understood. Cleft lip and/or cleft palate are caused by multiple genes inherited from both parents, as well as environmental factors that scientists do not yet fully understand. […] When a combination of genes and environmental factors cause a condition, the inheritance is called „multifactorial” (many factors contribute to the cause). Because genes are involved, the chance for a cleft lip and/or cleft palate to happen again in a family is increased, depending on how many people in the family have a cleft lip and/or cleft palate. […] If parents without clefts have a baby with a cleft, the chance for them to have another baby with a cleft ranges from 2 to 8 percent. If a parent has a cleft, but no children have a cleft, the chance to have a baby with a cleft is 4 to 6 percent. If a parent and a child have a cleft, the chance is even greater for a future child to be born with a cleft. Genetic consultation is suggested.

• #1 Cleft Lip & Cleft Palate: Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/10947-cleft-lip-cleft-palate

  Some studies suggest cleft lips and cleft palates have a genetic component. If you or your partner were born with a cleft lip or palate, your chance of having a baby with a cleft is around 2% to 8%. If you’ve already had a child with a cleft lip or palate, your chances of having another child with the condition are slightly higher.

• #1 Pediatric Cleft Lip and Palate: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/995535-overview

  Most orofacial clefts, like most common congenital anomalies, are caused by an interaction between genetic and environmental factors. In those instances, genetic factors create a susceptibility for clefts. When environmental factors (ie, triggers) interact with a genetically susceptible genotype, a cleft develops during an early stage of development. […] The relative proportions of environmental and genetic factors vary with the sex of the individual affected with cleft. In CL and CP, they also vary with the severity and the unilaterality or bilaterality of the cleft anomaly. […] Thus, the classic multifactorial threshold (MFT) model of liability can be applied to CL/P. […] A cleft develops when embryonic parts called processes (which are programmed to grow, move, and join with each other to form an individual part of the embryo) do not reach each other in time and an open space (cleft) between them persists.

• #1 Cleft Lip and Palate: Causes, Diagnosis, & Treatment – BuzzRx

  https://www.buzzrx.com/blog/cleft-lip-and-palate-causes-diagnosis-treatment

  Folic acid: Expectant mothers who do not take folic acid during early pregnancy have a 4-5 times higher risk of having babies with cleft lip and palate. […] Tobacco use: Women who smoke have a higher chance of having a baby with a cleft lip and palate. […] Alcohol use: Women who drink large amounts of alcohol (on at least 3 occasions with 5 or more drinks on each occasion) during early pregnancy are three times more likely to have an infant with cleft lip and palate. […] Diabetes: Women with a diagnosis of diabetes before pregnancy are at a higher risk of giving birth to a baby with a cleft lip and cleft palate. […] Obesity: There is some evidence that obese women are at an increased risk of having infants with cleft lip and cleft palate. […] Diet: A Western diet that is high in meats and processed foods and low in fruits is associated with an almost two-fold risk of having a baby born with cleft lip or cleft palate.

• #1 Causes of Cleft Lip & Palate – Department of Pediatrics

  https://med.virginia.edu/pediatrics/clinical-and-patient-services/patient-tutorials/cleft-lip-palate/causes-of-cleft-lip-palate/

  Some families have a history of clefting. There may be a grandparent, parent, cousin, brother or sister, or another relative who has had a cleft palate. This may be passed on from generation to generation. However, only 1 out of every 5 clefts are inherited. There are many children born with cleft palates who have no family history of clefting. […] Most cleft palates seem to be caused by environmental factors that increase a mothers risk of giving birth to a child with a cleft palate. […] These factors include: exposure to German measles (Rubella) or other infections, certain medications, alcohol and drug usage, cigarette smoking, certain vitamin deficiencies, especially during early pregnancy. […] The number of children born each year with cleft palates is growing. Some doctors and scientists believe this rise is caused by the recent increase in teenage pregnancies and the unavailability of proper prenatal care to many pregnant women.

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• #1 Cleft lip and cleft palate – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/cleft-lip-and-cleft-palate/

  Cleft lip (CL) and cleft palate (CP) are the most common congenital orofacial deformities. A combination of genetic predisposition and in-utero exposure to teratogens (nicotine, alcohol, antiepileptic drugs) can arrest the fusion of the facial processes required for normal facial development. Failure of fusion of the maxillary prominence with the medial nasal prominence causes cleft lip (CL). Failure of fusion of the palatine prominences causes cleft palate (CP). […] The development of CL/CP is dependent on the interaction of environmental factors and genetic predisposition. […] Genetic predisposition: Family history: multifactorial inheritance pattern (Mendelian inheritance is rare). […] Environmental factors: exposure to teratogenic substances in utero: Nicotine and/or alcohol. […] Drugs: antiepileptics; (e.g., phenytoin, sodium valproate, carbamazepine, phenobarbital), folate antagonists (e.g., methotrexate, trimethoprim), and excessive vitamin A intake during pregnancy. […] Partial or total failure of primary palate formation leads to cleft lip. Failed formation of the secondary palate leads to cleft palate.

• #1 Cleft Lip/Cleft Palate | Birth Defects | CDC

  https://www.cdc.gov/birth-defects/about/cleft-lip-cleft-palate.html

  Cleft lip and cleft palate are birth defects that occur when a baby’s lip or mouth don’t form properly. […] The causes of orofacial clefts among most infants are unknown. Cleft lip and cleft palate are thought to be caused by a combination of genes and other factors. […] CDC research has found some factors that increase the risk of having a baby with an orofacial cleft: Smoking during pregnancy, Having diabetes before pregnancy (type 1 or 2), Use of certain epilepsy medications during pregnancy.

• #1

  https://www.nhs.uk/conditions/cleft-lip-and-palate/

  A cleft lip or palate happens when the structures that form the upper lip or palate fail to join together when a baby is developing in the womb. […] The exact reason why this happens to some babies is often unclear. It’s very unlikely to have been caused by anything you did or did not do during pregnancy. […] In a few cases, cleft lip and palate is associated with: the genes a child inherits from their parents (although most cases are a one-off), smoking in pregnancy or drinking alcohol while pregnant, obesity during pregnancy, a lack of folic acid during pregnancy, taking certain medicines in early pregnancy, such as some anti-seizure medicines. […] In some cases, a cleft lip or palate can occur as part of a condition that causes a wider range of birth defects, such as 22q11 deletion syndrome (sometimes called DiGeorge or velocardiofacial syndrome) and Pierre Robin sequence.

• #1 Characteristics of Factors Influencing the Occurrence of Cleft Lip and/or Palate: A Case Analysis and Literature Review

  https://www.mdpi.com/2227-9067/11/4/399

  Cleft lip with or without cleft palate (CL/P) stands as the most common congenital facial anomaly, stemming from multifactorial causes. […] The etiology of cleft lip and palate involves both genetic and environmental factors, with recent findings supporting different causes for its three subtypes: cleft lip, cleft palate, and combined cleft lip and palate. […] Scientific and epidemiological research highlights the significant impact of environmental risk factors, including smoking, alcohol consumption, malnutrition during pregnancy, viral infections, teratogenic drugs, folate deficiency, and body mass, on the development of these congenital anomalies. […] The study investigated the influence of genetics, socio-economic status, and environmental factors on the incidence of bilateral cleft palates in children, uncovering significant associations. Notably, maternal stress during pregnancy emerged as a critical risk factor, increasing the likelihood of bilateral clefts by 9.4 times. […] The research underscores the complex interplay of factors contributing to the risk of cleft lip and palate, encompassing genetics, environmental influences, and lifestyle choices.

• #1 What Causes Cleft Lip?

  https://www.pcrf.net/information-you-should-know/what-causes-cleft-lip.html

  Cleft lip is a congenital birth defect that occurs when the tissues of the upper lip fail to properly fuse together during prenatal development. This results in a separation or „cleft” in the lip. A cleft can range from a small notch to a large opening that extends into the nose. […] The exact causes of cleft lip are not fully understood, but it is believed that a combination of genetic and environmental factors play a role. One of the most significant risk factors for cleft lip is a family history of the condition. Children born to parents who have a history of cleft lip are more likely to be born with the condition themselves. […] Other factors that have been associated with an increased risk of cleft lip include exposure to certain environmental toxins during pregnancy, such as tobacco or alcohol. Maternal illness including certain viral infections can also increase the risk of cleft lip, as can certain genetic disorders, like Down syndrome.

• #1 Cleft Lip and Cleft Palate: Incidence, Etiology and Development | IntechOpen

  https://www.intechopen.com/chapters/89204

  Environmental factors in isolation or interacting with genetic factors produce cleft lip and cleft palate. Example of environmental factors along with genetic factors causing the cleft lip and cleft palate is mutation in the gene PHF8. Investigators found that PHF8 encodes for a histone lysine demethylase and this gene regulates epigeneticity and is catalytic in action. But catalytic activity of PHF8 gene depends on the level of oxygen, i.e. less is oxygen more is catalytic activity. Increased incidence of cleft lip and palate has been observed in mice exposed to hypoxia (less of oxygen) during early pregnancy. So, it can be interpreted that environmental factors (hypoxia) in conjunction with genetic factors (PHF8 gene) cause cleft lip and cleft palate.

• #1 CHOP Study Finds Poverty Affects Risk of Cleft Lip and Cleft Palate | Children’s Hospital of Philadelphia

  https://www.chop.edu/news/chop-study-finds-poverty-affects-risk-cleft-lip-and-cleft-palate

  Indicators of lower socioeconomic status, such as lower maternal educational attainment and lack of prenatal care, are associated with an increased risk of cleft lip with or without cleft palate, according to a new study by researchers at Childrens Hospital of Philadelphia (CHOP). […] The researchers also found that most risk factors for cleft lip with or without cleft palate do not overlap with those for cleft palate only, supporting the hypothesis that cleft lip is more strongly linked with environmental factors, whereas cleft palate only is more strongly linked with genetic factors. […] The researchers found that both lower maternal education and lack of prenatal care were linked to an increased incidence of cleft lip with or without cleft palate. […] They also found that receiving WIC assistance was associated with an increase in the risk of cleft palate only, which could reflect eligibility criteria for WIC assistance.

• #1 Cleft Lip and Palate: Causes, Types, Treatment

  https://www.gillettechildrens.org/conditions-care/cleft-lip-and-palate

  Cleft lip (a separation in the upper lip) and cleft palate (a split in the roof of the mouth) are the most common types of conditions that affect the skull and face. Each year, the conditions affect one in every 700 babies born in the United States, according to Cleftline. […] Although no one knows exactly what causes clefts, some medical specialists believe that family history and environmental factors (such as medications or vitamin deficiencies) play roles. […] The likelihood of having a child who has a cleft increases slightly if a mother is older than 35 years old while she is pregnant. Either parent can pass on the gene or genes that cause clefts. Biological children of a parent who has a cleft have a 4- to 6-percent chance of also having clefts. […] Clefts occur more often among the Asian population and among certain groups of Native Americans. They occur less frequently among African Americans. More males have cleft lip or cleft lip with cleft palate; however, more females have cleft palate alone. […] Up to 13 percent of babies who have clefts have additional congenital conditions, some of which aren’t readily apparent. Genetic testing can help determine if a child’s cleft is part of an underlying condition.

• #1 Cleft lip and palate: Epidemiology and etiology

  https://www.oatext.com/cleft-lip-and-palate-epidemiology-and-etiology.php

  Cleft lip and palate are considered as one of the most common birth defects that result in medical, psychological, and social problems in affected individuals and their families. They have a complex etiology in which both genetic and environmental factors play a role. Risk factors such as vitamin deficiency, especially folic acid deficiency, and maternal smoking, alcohol consumption, drug use, and chemical exposure have been associated with cleft lip and palate development. […] The multifactorial inheritance model, which involves the interaction of genetic and environmental factors, is a good example for the epidemiological findings of nsCL/P. […] Cleft lip and palate is a multifactorial disease; it is caused by the interaction of genetic factors and environmental factors such as maternal smoking, alcohol consumption, inadequate nutritional intake of folic acid and vitamins B6 and B12, and chemical exposure during pregnancy.

• #1 Cleft Lip & Cleft Palate: Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/10947-cleft-lip-cleft-palate

  Cleft lip and cleft palate are separations in the upper lip and mouth that occur while a fetus develops in the uterus. A cleft lip and cleft palate are openings in a baby’s upper lip or roof of their mouth (palate). They’re congenital abnormalities (birth defects) that form while a fetus develops in the uterus. Cleft lips and cleft palates happen when tissues of the upper lip and roof of the mouth don’t join together properly during fetal development. […] In most cases, there’s no known cause of cleft lip or cleft palate, and parents can’t prevent it. Most scientists believe a combination of genetic (inherited) and environmental (related to the natural world) factors cause clefts. There seems to be a greater chance of a newborn having a cleft if a sibling, parent or other relative has one.

• #1 Cleft Lip & Palate Association

  https://www.clapa.com/what-is-cleft-lip-palate/what-causes-a-cleft/

  There is no single cause of cleft lip and/or palate. Research tells us it’s often caused by a combination of different genetic and environmental factors, but because of the huge number of factors involved it can be very difficult to narrow these down. […] Most of the time, a cleft is caused by genetic and environmental factors coming together in a way which can’t be predicted or prevented. […] Around 15% of clefts are caused by syndromes, where one or more symptoms occur all together. […] An isolated cleft palate (where the lip is not affected) is believed to have a different cause to cleft lip and palate. […] There are a huge number of factors that affect how likely someone is to have a cleft, including race, sex, and many different environmental factors that are almost impossible to predict without a careful look at an individual’s genetic history and circumstances.

• #1 Cleft Lip & Palate Association

  https://www.clapa.com/what-is-cleft-lip-palate/related-conditions-and-syndromes/

  Cleft lip and/or palate are listed as symptoms of over 400 various conditions and syndromes, although some are extremely rare. This means the cleft itself is caused by the condition or syndrome. […] It is estimated that around 15-30% of people born with a cleft are affected by one of these conditions or syndromes. Having a cleft alone does not mean that an individual has one of these conditions. Most people born with a cleft are ‘non-syndromic’ or ‘asyndromic’, meaning it isn’t linked to any wider issues. […] For most of these conditions, cleft palate (not cleft lip) is listed as a symptom. It is very difficult to detect a cleft palate before birth, but statistically just over half of people with a cleft lip will also have a cleft palate. Expectant parents with a diagnosis of cleft lip may, therefore, be told their child could have another condition. The chances of any of these will be different for each set of parents. As with a cleft lip and palate, sometimes there will be a clear genetic link and sometimes it will happen as a one-off in families.

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• #1 Cleft lip and palate: Epidemiology and etiology

  https://www.oatext.com/cleft-lip-and-palate-epidemiology-and-etiology.php

  Cleft lip and palate are considered as one of the most common birth defects that result in medical, psychological, and social problems in affected individuals and their families. It has a complex etiology in which both genetic and environmental factors play a role. Risk factors such as vitamin deficiency, especially folic acid deficiency, and maternal smoking, alcohol consumption, drug use, and chemical exposure have been associated with cleft lip and palate development. […] Identifying the factors contributing to cleft lip and palate etiology is important for preventing their development and for taking necessary measures. […] Cleft lip and palate are hereditary diseases in which environmental and genetic factors together play a role, leading to different clinical outcomes. […] Epidemiological studies and observational reports have shown that folic acid supplements taken by the mother before pregnancy have a protective effect in reducing the incidence of cleft lip and palate, whereas smoking and alcohol consumption before pregnancy increase the risk of cleft lip and palate formation.

• #1 Genetic etiology of cleft lip and cleft palate

  https://www.aimspress.com/article/id/5694

  Genetic studies in humans have demonstrated that Cleft lip with or without cleft palate (CL/P) have a diverse genetic background and probably environmental factors influencing these malformations. CL/P is one of the most common congenital birth defects in the craniofacial region with complex etiology involving multiple genetic factors, environmental factors and gene-environment interaction. […] The article describes the brief introduction of CL/P, epidemiology and general concepts, etiological factors, and the genes implicated in the etiology of nonsyndromic CL/P (NSCL/P) as suggested by different human genetic studies, animal models, and other expression studies.

• #2 Cleft Lip & Cleft Palate: Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/10947-cleft-lip-cleft-palate

  Cleft lip and cleft palate are separations in the upper lip and mouth that occur while a fetus develops in the uterus. A cleft lip and cleft palate are openings in a baby’s upper lip or roof of their mouth (palate). They’re congenital abnormalities (birth defects) that form while a fetus develops in the uterus. Cleft lips and cleft palates happen when tissues of the upper lip and roof of the mouth don’t join together properly during fetal development. […] In most cases, there’s no known cause of cleft lip or cleft palate, and parents can’t prevent it. Most scientists believe a combination of genetic (inherited) and environmental (related to the natural world) factors cause clefts. There seems to be a greater chance of a newborn having a cleft if a sibling, parent or other relative has one.

• #2 Cleft and/or cleft palate | Craniofacial Anomalies | UC Davis Children’s Hospital

  https://health.ucdavis.edu/children/patient-education/cleft-craniofacial-anomalies/cleft

  A cleft lip occurs when the lip did not quite close during the development before birth and needs to be surgically closed. […] A cleft palate is when there is an opening or cleft in the roof of the mouth due to the palate not closing during development before birth. […] Most of the time the cause of an isolated cleft lip and/or palate is not known. It is known that the risk of having a cleft is increased in babies of mothers who take certain seizure medications, are diabetic or who drink an excess of alcohol. Otherwise, it is probably caused by a combination of genes passed down from the mother and the father. There may also be some non-genetic factors that are not yet known. […] Early in our development we all have clefts. Our faces are spread out, but as we develop the face comes together and finally seals itself. The lips form between 4 and 6 weeks of pregnancy and the palate forms between 6 and 12 weeks of pregnancy. In babies born with a cleft the sealing did not quite finish.

• #2 Pediatric Cleft Lip and Palate: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/995535-overview

  Most orofacial clefts, like most common congenital anomalies, are caused by an interaction between genetic and environmental factors. In those instances, genetic factors create a susceptibility for clefts. When environmental factors (ie, triggers) interact with a genetically susceptible genotype, a cleft develops during an early stage of development. […] The relative proportions of environmental and genetic factors vary with the sex of the individual affected with cleft. In CL and CP, they also vary with the severity and the unilaterality or bilaterality of the cleft anomaly. […] Thus, the classic multifactorial threshold (MFT) model of liability can be applied to CL/P. […] A cleft develops when embryonic parts called processes (which are programmed to grow, move, and join with each other to form an individual part of the embryo) do not reach each other in time and an open space (cleft) between them persists.

• #2 Cleft Lip and Cleft Palate: Incidence, Etiology and Development | IntechOpen

  https://www.intechopen.com/chapters/89204

  Cleft lip and palate are birth defects or congenital in nature occurring during development. The cause is unknown but risk factors attributing to this facial anomaly are smoking, diabetes, obesity, increased age of mother and certain drugs used during pregnancy. Cleft lip and palate are considered to be polygenic and multifactorial in origin with involvement of many genetic and environmental factors. Literature reports that the cleft lip and palate are due to involvement of genetic factors in 20 to 50% of cases and in rest of the cases, these facial anomalies are reported to be caused by environmental factors or a combination of gene and environmental factors. Few authors are of the view that people with polygenic/multifactorial inheritance are born without cleft lip and cleft palate but umpteen number of genetic and environmental factors are said attributed to cleft lip and palate.

• #2 Cleft Lip & Palate Association

  https://www.clapa.com/what-is-cleft-lip-palate/related-conditions-and-syndromes/

  Cleft lip and/or palate are listed as symptoms of over 400 various conditions and syndromes, although some are extremely rare. This means the cleft itself is caused by the condition or syndrome. […] It is estimated that around 15-30% of people born with a cleft are affected by one of these conditions or syndromes. Having a cleft alone does not mean that an individual has one of these conditions. Most people born with a cleft are ‘non-syndromic’ or ‘asyndromic’, meaning it isn’t linked to any wider issues. […] For most of these conditions, cleft palate (not cleft lip) is listed as a symptom. It is very difficult to detect a cleft palate before birth, but statistically just over half of people with a cleft lip will also have a cleft palate. Expectant parents with a diagnosis of cleft lip may, therefore, be told their child could have another condition. The chances of any of these will be different for each set of parents. As with a cleft lip and palate, sometimes there will be a clear genetic link and sometimes it will happen as a one-off in families.

• #2 Genetic Syndrome Causes Cleft Lip, Palate in Sisters – CHOC – Children’s health hub

  https://health.choc.org/genetic-syndrome-causes-cleft-lip-palate-in-sisters/

  Van der Woude syndrome is the most common single-cause of cleft lip and palate. […] „If a child’s mother or father has Van der Woude syndrome, each child would have a 50 percent chance of also having the condition,” according to Dr. Neda Zadeh, a CHOC genetic specialist. […] „VWS can present differently in each person. For instance, a mom may have had lip pits, but her child could have a cleft palate and no evidence of lip pits.”

• #2 Cleft Lip and Cleft Palate: Incidence, Etiology and Development | IntechOpen

  https://www.intechopen.com/chapters/89204

  Environmental factors in isolation or interacting with genetic factors produce cleft lip and cleft palate. Example of environmental factors along with genetic factors causing the cleft lip and cleft palate is mutation in the gene PHF8. Investigators found that PHF8 encodes for a histone lysine demethylase and this gene regulates epigeneticity and is catalytic in action. But catalytic activity of PHF8 gene depends on the level of oxygen, i.e. less is oxygen more is catalytic activity. Increased incidence of cleft lip and palate has been observed in mice exposed to hypoxia (less of oxygen) during early pregnancy. So, it can be interpreted that environmental factors (hypoxia) in conjunction with genetic factors (PHF8 gene) cause cleft lip and cleft palate.

• #2 Cleft Lip & Palate Association

  https://www.clapa.com/what-is-cleft-lip-palate/what-causes-a-cleft/

  If there is one parent with a cleft, the likelihood of a child having a cleft is between 2-8%, although in some cases depending on the cause of the parent’s cleft it can be as high as 50%. […] It is important to remember that a cleft may be caused by another condition or syndrome which has not been diagnosed, in which case the chances of inheriting the cleft will be very different. […] Where there is no family history and the cleft was not caused by a syndrome or condition, the likelihood of having a child with a cleft is around 0.14%, or 1/700.

• #2 Orofacial Clefts: Genetics of Cleft Lip and Palate

  https://www.mdpi.com/2073-4425/14/8/1603

  The evidence of underlying genetic factors influencing the risk of developing oral cleft was supported by twin studies. An orofacial cleft population-based cohort study has shown that the relative recurrence risk for CL was 32, and CP was found to be 65 times higher among first-degree relatives. […] Environmental factors are also known to play a crucial role in nonsyndromic cleft lip and palate pathogenesis through interactions with different genes in susceptible individuals. For example, several studies have shown that the association is significant between maternal smoking and nonsyndromic orofacial clefts, which is also applicable to passive smoking. However, this association is not strong, as studies have shown that the risk for orofacial clefts secondary to smoking during pregnancy is minor, with an odds ratio of around 1.3 for CLP.

• #2 Pediatric Cleft Lip and Palate: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/877970-overview

  Most orofacial clefts, like most common congenital anomalies, are caused by an interaction between genetic and environmental factors. […] The relative proportions of environmental and genetic factors vary with the sex of the individual affected with cleft. […] Thus, the classic multifactorial threshold (MFT) model of liability can be applied to CL/P. […] A cleft develops when embryonic parts called processes do not reach each other in time and an open space (cleft) between them persists. […] In general, any factor that could prevent the processes from reaching each other would cause a cleft to persist. […] There has been considerable interest in identifying genes that contribute to the etiology of orofacial clefting. […] The first candidate gene was transforming growth factor- (TGFA), which showed an association with nonsyndromic CLP in a White population. […] Other candidate genes that were described as being associated with nonsyndromic CLP included D4S192, RARA, MTHFR, RFC1, GABRB3, PVRL1, and IRF6. […] The identification of factors that contribute to the etiology of nonsyndromic CL/P is important for prevention, treatment planning, and education.

• #2 Cleft Lip and Palate: Causes, Treatment, and Outlook

  https://patient.info/ears-nose-throat-mouth/cleft-lip-and-palate-leaflet

  Cleft lip and palate are facial abnormalities which can affect babies at birth. […] The exact cause is not known. It is thought to involve a mixture of genetic and environmental factors affecting the baby in the womb (uterus). 'Genetic’ means that the condition is passed on through families through their genes. […] There is some evidence that women diagnosed with diabetes before pregnancy may have an increased risk of having a baby with a cleft lip with or without a cleft palate. […] There is some evidence that babies born to women with obesity may have increased risk of CLP palate. […] Some types of medicines, if taken during early pregnancy, are known to increase the risk. These include some epilepsy medicines such as phenytoin, isotretinoin, and sodium valproate. […] Smoking around the time of conception and in the first ten weeks seems to increase the risk. […] Alcohol use in the first twelve weeks of pregnancy, particularly if you are binge drinking, also increases the risk. […] The failure of development of the upper lip and palate occurs early in pregnancy, between the fifth and ninth weeks.

• #2 Cleft lip and cleft palate – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/cleft-lip-and-cleft-palate/

  Cleft lip (CL) and cleft palate (CP) are the most common congenital orofacial deformities. A combination of genetic predisposition and in-utero exposure to teratogens (nicotine, alcohol, antiepileptic drugs) can arrest the fusion of the facial processes required for normal facial development. Failure of fusion of the maxillary prominence with the medial nasal prominence causes cleft lip (CL). Failure of fusion of the palatine prominences causes cleft palate (CP). […] The development of CL/CP is dependent on the interaction of environmental factors and genetic predisposition. […] Genetic predisposition: Family history: multifactorial inheritance pattern (Mendelian inheritance is rare). […] Environmental factors: exposure to teratogenic substances in utero: Nicotine and/or alcohol. […] Drugs: antiepileptics; (e.g., phenytoin, sodium valproate, carbamazepine, phenobarbital), folate antagonists (e.g., methotrexate, trimethoprim), and excessive vitamin A intake during pregnancy. […] Partial or total failure of primary palate formation leads to cleft lip. Failed formation of the secondary palate leads to cleft palate.

• #2 Cleft Lip and Palate: Causes, Diagnosis, & Treatment – BuzzRx

  https://www.buzzrx.com/blog/cleft-lip-and-palate-causes-diagnosis-treatment

  The exact cause of cleft lip and cleft palate is unknown, but it is believed to be a mix of genetic and environmental factors, including medications and the mothers environment during pregnancy. […] The exact cause of cleft lip and cleft palate is unknown. It is believed to be a mix of genetic and environmental factors, including certain medications and the mothers environment during the pregnancy, such as vitamin deficiency and tobacco or substance use. […] Some of the known risk factors for cleft lip and cleft palate include: Family history: Cleft lip and cleft palate affect babies more often if there is a family history of cleft and craniofacial conditions. […] Certain medicines: Women who take certain anti-seizure medicines, such as valproic acid and topiramate, during the first trimester are at an increased risk of having a baby with a cleft palate and cleft lip. Other medications that can increase the risk of this congenital disorder include Accutane, an acne medication, and methotrexate, a medication used for cancer and other autoimmune diseases such as rheumatoid arthritis or psoriasis.

• #2 Causes and Solutions of Cleft Palates – Sedaros Oral Surgery

  https://www.sedarosoralsurgery.com/blog/causes-solutions-cleft-palates/

  Two developmental defects that occur during the first trimester of pregnancy are the cleft palate and the cleft lip: These oral and facial malformations are frequently referred to as clefting. […] Clefting occurs when there is an inadequate amount of tissue in the lip and/or mouth area, and the tissue that does exist neglects to come together properly (fuse). Each year, one in 700 babies are born with some form of clefting. […] In the majority of cases, the cause of clefting is unknown; however, scientists do believe that a combination of environmental and genetic factors play a role in causing these malformations. […] Clefting may also occur when the developing fetus is exposed to chemicals, viruses and/or medications. […] Some of the medications believed to cause clefting include: acne medications that contain Accutane; medications like Topamax that are used to treat migraine headaches; anticonvulsant/anti-Seizure medications; as well as methotrexate, which is a medication frequently used to treat psoriasis, arthritis and cancer.

• #2 Cleft Lip and Cleft Palate Causes, Signs and Screening at OHSU

  https://www.ohsu.edu/doernbecher/cleft-lip-and-cleft-palate

  Cleft lip and cleft palate are common birth defects, and the most common medical issue affecting the head and neck. Each year in the United States, about 2,650 babies are born with a cleft palate and about 4,440 babies are born with a cleft lip, according to the Centers for Disease Control. […] Heredity plays a role in cleft lip and cleft palate. You have a higher risk of having a baby with a cleft if you already had a baby with a cleft or if you or your partner has a cleft. […] Cleft lip and cleft palate are usually not linked to environmental factors. But researchers continue to study behaviors that may affect a baby’s development in early pregnancy. […] According to the CDC, these factors may increase the risk of cleft lip or cleft palate. […] Parents who smoke during pregnancy have a higher risk of having a baby with a cleft. […] Parents with diabetes diagnosed before pregnancy (not gestational diabetes) have a higher risk of having a baby with a cleft. […] Parents who use certain medicines to treat epilepsy, such as topiramate or valproic acid, during the first trimester have a higher risk of having a baby with a cleft.

• #2 CHOP Study Finds Poverty Affects Risk of Cleft Lip and Cleft Palate | Children’s Hospital of Philadelphia

  https://www.chop.edu/news/chop-study-finds-poverty-affects-risk-cleft-lip-and-cleft-palate

  The study also confirmed known environmental risk factors for orofacial clefts, such as maternal smoking, maternal obesity, and gestational diabetes. […] Future studies are needed to elucidate the mechanisms underlying the relationship between socioeconomic status and risks of cleft lip with or without cleft palate and cleft palate only in order to improve and implement public health policies aimed at reducing the burden of clefts and its disproportionate impact on the socioeconomically disadvantaged populations.

• #2 Cleft Lip and Cleft Palate | familydoctor.org

  https://familydoctor.org/condition/cleft-lip-cleft-palate/

  Cleft lip and cleft palate are defects that occur early in pregnancy. A baby’s facial features develop in the first trimester (3 months). The lips form first, followed by the mouth and palate. Clefts occur if the tissues and cells don’t form right. Cleft lip and cleft palate can occur by themselves. They also can be part of another condition or syndrome. […] No one knows exactly what causes clefts. Doctors believe it’s due to factors from genetics or the environment. There are certain things that could increase your risk of having a baby with a cleft. These include: Having a family history of cleft lip or palate. Using tobacco, drugs, or alcohol during pregnancy. Not getting enough nutrients during pregnancy, such as folic acid. Having diabetes before pregnancy. Taking certain medicines, such as some for epilepsy, during pregnancy. Obesity during pregnancy. Having certain infections during pregnancy, such as rubella (German measles).

• #2 Cleft lip and palate: Epidemiology and etiology

  https://www.oatext.com/cleft-lip-and-palate-epidemiology-and-etiology.php

  Cleft lip and palate are considered as one of the most common birth defects that result in medical, psychological, and social problems in affected individuals and their families. It has a complex etiology in which both genetic and environmental factors play a role. Risk factors such as vitamin deficiency, especially folic acid deficiency, and maternal smoking, alcohol consumption, drug use, and chemical exposure have been associated with cleft lip and palate development. […] Identifying the factors contributing to cleft lip and palate etiology is important for preventing their development and for taking necessary measures. […] Cleft lip and palate are hereditary diseases in which environmental and genetic factors together play a role, leading to different clinical outcomes. […] Epidemiological studies and observational reports have shown that folic acid supplements taken by the mother before pregnancy have a protective effect in reducing the incidence of cleft lip and palate, whereas smoking and alcohol consumption before pregnancy increase the risk of cleft lip and palate formation.

• #2 Cleft Lip and Palate in Children | Phoenix Children’s Hospital

  https://phoenixchildrens.org/specialties-conditions/cleft-lip-and-palate-children

  Cleft lip and cleft palate happen when a baby develops in the mother’s uterus. Researchers don’t know the exact cause of cleft lip and palate. It can be caused by genes passed on from parents, as well as environmental factors. Environmental factors include taking certain medicines during pregnancy, smoking or drinking alcohol during pregnancy, infections, and getting too little vitamin B and folic acid during pregnancy. Parents who have cleft lip, cleft palate, or both, or who have other kids with the problem are at an increased risk of having babies with the defect. […] Genes and the environment are involved, but the cause is not completely understood.

• #2 Cleft Lip and Palate: What it Is and How to Prevent It –

  https://www.carnegieimaging.com/blog/cleft-lip-and-palate-what-it-is-and-how-to-prevent-it/

  What is Cleft Lip and Cleft Palate? A cleft lip or cleft palate happens when your baby’s upper lip and mouth doesn’t form completely. This results in an opening and is present at birth. Oral clefts (or orofacial clefts) occur in about 1 in 1,000 babies in the United States, meaning it’s a relatively common birth defect. It often happens early in pregnancy, or between 4 and 9 weeks of gestation, and male babies are more likely to have a cleft lip (with or without a cleft palate) than female babies, but female babies are more likely to have a cleft palate without a cleft lip. […] What causes oral clefts? It’s not well understood what causes oral clefts, although there are some things that seem to increase the risk. This usually includes genetic and environmental factors. These include: A family history of oral clefts. Oral clefts can be more common in families of Asian, Hispanic, and Native American descent, Substance use during pregnancy, Nutrient deficiency, specifically of folic acid, Having diabetes before pregnancy, Use of certain anti-seizure medications, Obesity during pregnancy, Certain infections like rubella.

• #2 What to know about cleft lip and palate

  https://www.babycenter.com/health/conditions/cleft-lip-and-palate_40008530

  Cleft lip and cleft palate are among the most common birth defects worldwide. In about 15 to 30 percent of cases, a cleft lip or palate appears as part of another medical condition. […] Genetics. Cleft palate tends to run in families. And cleft lip or palate appears in more than 200 different syndromes with known genetic causes. […] Some studies show that clefts are more common among Asian and Hispanic people, and less common among Black people. […] If you have a family history of cleft lip or palate, your doctor may advise genetic counseling to get a better understanding of your risks. […] Studies have shown that people born with clefts have higher rates of mental illness and higher rates of certain cancers, which could be related to the genetic cause of the cleft.

• #2 Cleft Lip and Palate: Causes, Diagnosis and Treatment

  https://www.nationwidechildrens.org/family-resources-education/700childrens/2016/11/cleft-lip-and-palate-causes-diagnosis-and-treatment

  Cleft lip and/or palate is the most common birth defect in the United States, affecting one of every 700 babies born, which means, on average, 16 babies are born every day in this country with a cleft. […] Clefts of the lip and/or palate occur early in pregnancy, during the first trimester, as a result of the failure of the separate parts of the lip and palate to come together during development. […] A variety of factors can increase the risk of a baby being born with a cleft lip or palate. Prenatal exposure to alcohol, cigarettes, and other medications and drugs increases the risk, but in most instances, there is no single explanation. Instead, a combination of many factors is the usual cause. In some cases, clefts occur as part of a genetic syndrome that often includes other birth defects. […] In most cases, cleft lip with or without cleft palate as well as isolated cleft palate occur alone and are believed to be due to multifactorial causation. This means that a variety of both genetic and non-genetic factors work together to result in a cleft.

• #2 Etiology, prenatal diagnosis, obstetric management, and recurrence of cleft lip and/or palate – UpToDate

  https://www.uptodate.com/contents/etiology-prenatal-diagnosis-obstetric-management-and-recurrence-of-cleft-lip-and-or-palate

  Etiology, prenatal diagnosis, obstetric management, and recurrence of cleft lip and/or palate […] Nonsyndromic cases […] Genetic factors […] Environmental factors […] Syndromic cases […] The oral cleft is the most common congenital craniofacial anomaly. The three main types are cleft lip alone, cleft palate alone, and cleft lip with cleft palate. Cleft lip with or without a cleft palate (CL/P) and cleft palate alone (CP) differ with respect to embryology, etiology, candidate genes, associated abnormalities, and recurrence risk.

• #2 What Causes Cleft Lips and Palates? – Dell Children’s Craniofacial Team of Texas

  https://craniofacialteamtexas.com/cleft-lip-and-cleft-palate/what-causes-cleft-lips-and-palates/

  “What Causes Cleft Lips and Palates?” is one of the most common questions we hear from parents of children with cleft lips and palates, and why this happened to their child, and whether something could be done differently to prevent clefting in other children. Although it has been extensively studied, we do not know exactly what causes cleft lips and palates. […] We do not know exactly what causes cleft lips and palates. […] The causes of nonsyndromic orofacial clefts are thought to be multifactorial, which means that a combination of genetic and environmental factors contributes to development of the cleft. The majority of cleft patients have no identifiable cause. The strongest risk factor for development of a cleft is family history. Other risk factors include maternal smoking, consumption of large amounts of alcohol during the first trimester of pregnancy, certain medications taken during the first trimester, and maternal diabetes mellitus (but not gestational diabetes). There has been shown to be a decreased risk of cleft lip and palate with the use of prenatal vitamins and folic acid.

• #2 Genetic etiology of cleft lip and cleft palate

  https://www.aimspress.com/article/id/5694

  Genetic studies in humans have demonstrated that Cleft lip with or without cleft palate (CL/P) have a diverse genetic background and probably environmental factors influencing these malformations. CL/P is one of the most common congenital birth defects in the craniofacial region with complex etiology involving multiple genetic factors, environmental factors and gene-environment interaction. […] The article describes the brief introduction of CL/P, epidemiology and general concepts, etiological factors, and the genes implicated in the etiology of nonsyndromic CL/P (NSCL/P) as suggested by different human genetic studies, animal models, and other expression studies.

• #2 Cleft lip and cleft palate – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/cleft-palate/diagnosis-treatment/drc-20370990

  Most cases of cleft lip and cleft palate are seen right away at birth, so special tests aren’t needed. […] Cleft lip and cleft palate are often seen on ultrasound before a baby is born. […] If cleft lip or cleft palate is found before birth, your healthcare professional will often recommend that you meet with a genetic counselor. […] But the cause of cleft lip and cleft palate most often isn’t known. […] The goals of treatment for cleft lip and cleft palate are to make it easier for a child to eat, speak and hear and achieve a typical look for the face. […] Treatment involves surgery to repair cleft lip and cleft palate and therapies to make any related conditions better. […] Surgery to correct a cleft lip and cleft palate is based on your child’s situation. […] Some children with more-severe clefts of the lip and palate may need orthodontic treatment before surgery to bring the edges of the cleft closer.

• #2 Cleft Lip and Cleft Palate

  https://dph.illinois.gov/topics-services/prevention-wellness/oral-health/fast-facts-oral-health/cleft-lip-and-cleft-palate.html

  Cleft lip/palate occurs when a babys lip or mouth do not form properly during pregnancy. It is the fourth most common birth defect and occurs in 1 in every 1,600 babies in the United States. […] The causes of clefts among most infants are unknown, but some are believed to be due to changes in their genes, or a combination of other factors, like things the mother comes in contact within her environment or what the mother eats or drinks. Recent research studies have also found some factors increase the chance of having a baby with a cleft, such as: smoking, diabetes, use of medications during pregnancy. […] Regular prenatal care can help reduce the risks of birth defects.

• #2 Orofacial Clefts: Genetics of Cleft Lip and Palate

  https://www.mdpi.com/2073-4425/14/8/1603

  Despite the growth in our understanding of the genetic etiology of syndromic orofacial clefts by the identification of many monogenic syndromes, which has been assisted by the rapid advance in genomics and genetics technology, the progress in our understanding of the genetic etiology of nonsyndromic orofacial clefting remains relatively slow in comparison to the syndromic type. This could be explained by the genetic heterogenicity of nonsyndromic orofacial clefts, the contribution of environmental factors and gene–environment interaction, and its deviation from the Mendelian inheritance, as most of the cases seems to be sporadic, despite the compelling evidence of a genetic component collected from twin studies.

• #3 Cleft of lip and palate: A review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7491837/

  Cleft of lip and palate are most common serial congenital anomalies to affect the orofacial region. It can occur isolated or together in various combination and/or along with other congenital deformities particularly congenital heart diseases. Clefts arises during the fourth developmental stage. Exactly where they appears is determined by locations at which fusion of various facial processes failed to occur, this in turn is influenced by the time in embryologic life when some interference with development occurred. In the developed world, most scientists believe that clefts occur due to a combination of genetic and environmental factors (e.g., maternal illness, drugs, malnutrition). Overall incidence of cleft lip and palate is approximately 1 in 600 to 800 live births (1.42 in 1000) and isolated cleft palate occurs approximately in 1 in 2000 live births. The potential problems of the condition include social handicaps such as impaired suckling and resultant failure to thrive, speech impediment, deafness, malocclusion, gross facial deformity and severe psychological problems. The etiology of cleft lip and palate is complex and thought to involve genetic influences with variable interactions from environmental factors. The etiological factors of cleft lip and palate can be grouped as under: Non-genetic: this includes various environmental (teratogenic) risk factors which may cause CL/P. Genetic cause includes: Syndromic: Here cleft is associated with other malformation. Usually it is due to a single gene (monogenic or Mendelian) disorder. Non-syndromic: Here the cleft is mostly an isolated feature and occurs in the vast majority of individuals having a cleft lip or palate (up to 70% cases). In this form, a cleft is neither a recognized pattern of malformation nor a known cause for the disorder can be identified. Various environmental factors includes: Smoking: The relationship between maternal smoking and CLP is not strong, but it is significant. Several studies have consistently yielded a relative risk of about 1.31.5. Alcohol use: Heavy maternal drinking, apart from causing fetal alcohol syndrome, also increases the risk of CLP. Others: Environmental factor includes maternal diseases, stress during pregnancy chemical exposure. Genetic factor: Various epidemiological observation have laid the foundation of role of genetics in etiology of cleft lip and palate. Many studies have shown that monozygotic twins (60%) have considerable higher concordance rate than dizygotic twins and siblings (5-10%). Syndromic form of cleft lip and palate: It accounts for more than 400 known syndromes and many of them follows classic Mendelian inheritance pattern. Non-syndromic form of cleft lip and palate: It accounts for 70% of CL/P cases and 50% of all CPO cases.

• #3 What Causes Cleft Lips and Palates? – Dell Children’s Craniofacial Team of Texas

  https://craniofacialteamtexas.com/cleft-lip-and-cleft-palate/what-causes-cleft-lips-and-palates/

  The risk of a future child being born with a cleft lip or palate also depends on whether the cleft is associated with a syndrome. Patients with syndromic clefts may have a known risk of clefting for siblings or children. […] For patients with sporadic, or nonsyndromic clefts, there is a small risk for recurrence, or for the cleft to occur in future siblings or children. […] By the time of the first ultrasound in which the fetus’ facial structures can be identified, clefting of the lip or palate will already have occurred. Development of the facial structures and form occurs between the 4th and 8th weeks of gestation. […] Failure of this process results in a cleft lip. […] Failure of fusion results in a cleft palate.

• #3 Cleft Lip and Cleft Palate – ENT Health

  https://www.enthealth.org/conditions/cleft-palate/

  No one knows exactly what causes clefts, but most believe they are caused by one or more of three main factors: (1) an inherited characteristic (gene) from one or both parents; (2) poor early pregnancy health or exposure to toxins such as alcohol or cocaine; and/or (3) genetic syndromes. A syndrome is an abnormality in genes or chromosomes that result in multiple malformations in a recognizable pattern occurring together. […] Cleft lip/palate is a part of more than 400 syndromes including Waardenburg, Pierre Robin, and Down syndromes. Approximately 30 percent of cleft deformities are associated with a syndrome, so a thorough medical evaluation and genetic counseling is recommended for cleft patients.

• #3

  https://www.cleftprevention.org/learn/articles/etiology-causes-of-cleft-lip-and-palate/

  Murray JC. Gene/environment causes of cleft lip and/or palate. Clin Genet 2002: 61: 248256. […] Saleem K, Zaib T, Sun W, Fu S. Assessment of candidate genes and genetic heterogeneity in human nonsyndromic orofacial clefts specifically non syndromic cleft lip with or without palate. Heliyon 5 (2019) e03019 […] Hur JS, Costanzo CJ, Baek SH, Tolar M, Mortazavi M, Tolarova MM. Association of RFC1 A80G Gene Polymorphism with Nonsyndromic Cleft Lip and Palate in Hispanics from Venezuela and Guatemala. Journal of Korean Cleft Lip Palate Association. 2021;24(1):1-9 […] Aljabeiti AS, Salahuddin R, Tolar M, Tolarova MM. Association of TGF3 variants with Nonsyndromic Cleft Lip and Palate in Guatemalan Population. J Den Craniofac Res Vol.2:No.1:9, 2017

• #3 Cleft Palate and Cleft Lip Difference, Causes, Treatment

  https://www.medicinenet.com/cleft_palate_and_cleft_lip/article.htm

  The large majority of infants experiencing cleft lip or cleft palate do not have a genetic predisposition or obvious risk factors. During pregnancy, some issues may increase the likelihood of producing a newborn with cleft lip and/or cleft palate. These may include the following: Certain medications to help prevent maternal seizures or migraine headaches (for example, topiramate [Topamax]), Certain medications that are used as cancer chemotherapy (including methotrexate [Rheumatrex, Trexall]), Smoking cigarettes (no information yet regarding e-cigarettes), Alcohol consumption, Lack of folic acid supplementation before conception and throughout the pregnancy.

• #3 Orofacial Clefts: Genetics of Cleft Lip and Palate

  https://www.mdpi.com/2073-4425/14/8/1603

  Despite the growth in our understanding of the genetic etiology of syndromic orofacial clefts by the identification of many monogenic syndromes, which has been assisted by the rapid advance in genomics and genetics technology, the progress in our understanding of the genetic etiology of nonsyndromic orofacial clefting remains relatively slow in comparison to the syndromic type. This could be explained by the genetic heterogenicity of nonsyndromic orofacial clefts, the contribution of environmental factors and gene–environment interaction, and its deviation from the Mendelian inheritance, as most of the cases seems to be sporadic, despite the compelling evidence of a genetic component collected from twin studies.

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