Materiały źródłowe

• #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.

• #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.

• #3 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.

• #4 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/

  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.

• #5 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.

• #6 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.

• #7 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.

• #8 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.

• #9 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.

• #10 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.

• #11 Genetic etiology of cleft lip and cleft palate

  https://www.aimspress.com/article/doi/10.3934/molsci.2020016?viewType=HTML

  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.

• #12 Genetic etiology of cleft lip and cleft palate

  https://www.aimspress.com/article/10.3934/molsci.2020016

  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.

• #13 Cleft Palate – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563128/

  Cleft palate arises from abnormal development of the palate or surrounding structures during gestation. […] Significant heterogeneity exists in the molecular pathways associated with the development of CL/P and CPO. […] A clear familial association between CL/P and CPO is present, as clefts in parents and siblings also increase the risk that a subsequent child will be affected. […] Cleft lip and palate, one of the most common congenital craniofacial abnormalities, is characterized by failure of normal fusion of the palate and lip during development, resulting in a clinically evident discontinuity of the lip or palate at birth. […] CL/P and CPO are found in over 200 different congenital syndromes. […] The pathways associated with the formation of the lip and palate include the sonic hedgehog pathway (SHH and SPRY2 genes), which interacts closely with the bone morphogenic pathway (BMP4 and BMP2 genes), fibroblast growth factor pathways (FGF10 and FGF7 genes), and transforming growth factor-beta (TGF) receptors and ligands.

• #14 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.

• #15 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.

• #16 Cleft Lip and Palate Clinic Conditions We Treat | Texas Children’s

  https://www.texaschildrens.org/departments/cleft-lip-and-palate-clinic/conditions-we-treat

  Cleft lip and palate is the result of abnormal fusion of the facial structures during pregnancy. Patients are diagnosed at birth by the presence of a gap or crack of the lip and/or palate. The range of severity for this defect can be quite wide. Cleft lip and/or palate occurs in approximately 1 in 1000 births. […] Smoking during pregnancy and fetal exposure to phenytoin (a drug used to treat seizures) can cause cleft lip and palate. Children of Asian descent have a higher incidence of cleft lip and palate. […] A family history of cleft lip and/or palate is also a risk factor for the condition. If the parent or sibling has a cleft lip and palate, the risk that your next child will have the disorder is 4%. If two siblings have cleft lip and palate, the risk of a subsequent child increases to 9%. If the parent and a child have cleft lip and palate, then the risk of the next child having the disorder goes to 17%. For isolated cleft palate, the risk of subsequent pregnancies with the disorder is 2% with one affected child and 6% if the parent had a cleft palate.

• #17 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.

• #18 Cleft Palate – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563128/

  A child of an affected parent has a 3% to 4% risk of CL/P and about 6% of CPO. […] Approximately 50% of CPO cases are associated with other congenital anomalies, more frequent than CL/P, which is associated with a congenital syndrome in about 15% of cases. […] The most commonly discussed are CHARGE (coloboma, heart defects, atresia choanae, growth retardation, genital abnormalities, and ear abnormalities) syndrome and velocardiofacial or DiGeorge syndrome (22q11.2 deletion). […] A clear environmental impact on the development of CL/P and CPO has been shown. […] Risk factors for malformation include smoking, diabetes, gestational diabetes, and teratogen exposure (eg, valproic acid, phenytoin, retinoic acid, dioxin, and thalidomide).

• #19 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.

• #20 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 other—for 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 location—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. […] Zucchero et al reported that variants of IRF6 may be responsible for 12% of nonsyndromic cleft lip and palate, suggesting that this gene would play a substantial role in the causation of orofacial clefts. […] The identification of factors that contribute to the etiology of nonsyndromic CL/P is important for prevention, treatment planning, and education.

• #21 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 other—for 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 location—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. […] Zucchero et al reported that variants of IRF6 may be responsible for 12% of nonsyndromic cleft lip and palate, suggesting that this gene would play a substantial role in the causation of orofacial clefts. […] The identification of factors that contribute to the etiology of nonsyndromic CL/P is important for prevention, treatment planning, and education.

• #22 Cleft Palate – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563128/

  Cleft palate arises from abnormal development of the palate or surrounding structures during gestation. […] Significant heterogeneity exists in the molecular pathways associated with the development of CL/P and CPO. […] A clear familial association between CL/P and CPO is present, as clefts in parents and siblings also increase the risk that a subsequent child will be affected. […] Cleft lip and palate, one of the most common congenital craniofacial abnormalities, is characterized by failure of normal fusion of the palate and lip during development, resulting in a clinically evident discontinuity of the lip or palate at birth. […] CL/P and CPO are found in over 200 different congenital syndromes. […] The pathways associated with the formation of the lip and palate include the sonic hedgehog pathway (SHH and SPRY2 genes), which interacts closely with the bone morphogenic pathway (BMP4 and BMP2 genes), fibroblast growth factor pathways (FGF10 and FGF7 genes), and transforming growth factor-beta (TGF) receptors and ligands.

• #23 Cleft Palate – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563128/

  Cleft palate arises from abnormal development of the palate or surrounding structures during gestation. […] Significant heterogeneity exists in the molecular pathways associated with the development of CL/P and CPO. […] A clear familial association between CL/P and CPO is present, as clefts in parents and siblings also increase the risk that a subsequent child will be affected. […] Cleft lip and palate, one of the most common congenital craniofacial abnormalities, is characterized by failure of normal fusion of the palate and lip during development, resulting in a clinically evident discontinuity of the lip or palate at birth. […] CL/P and CPO are found in over 200 different congenital syndromes. […] The pathways associated with the formation of the lip and palate include the sonic hedgehog pathway (SHH and SPRY2 genes), which interacts closely with the bone morphogenic pathway (BMP4 and BMP2 genes), fibroblast growth factor pathways (FGF10 and FGF7 genes), and transforming growth factor-beta (TGF) receptors and ligands.

• #24 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. […] Maternal hypoxia due to smoking by pregnant women may also lead to cleft lip. In 6.1% of cases, children were found to born with cleft lip and palate with women smoking during pregnancy. One important point to note here is that cleft lip and palate occur in very early pregnancy, so, stopping smoking after diagnosis of pregnancy may not reduce the incidence of these clefts. Alcohol intake during pregnancy has also been attributed to cleft lip and palate as alcohol influences the development of cranial neural crest cells. But degree of influence of alcohol on neural crest cells is unknown and requires further research. There is evidence of causing cleft lip and palate in children of women who received anti-hypertensive treatment during pregnancy. Various other factors causing cleft lip and palate include pesticide exposure, maternal diet, retinoid intake, anticonvulsant drugs like nitrate compounds, organic solvents, parental exposure to lead, alcohol, cigarette use and intake of psychoactive drugs such as cocaine, crack cocaine and heroin.

• #25 Cleft lip and cleft palate – Wikipedia

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

  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. […] 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 lysine demethylase, and is involved in epigenetic regulation. […] Cleft lip and other congenital abnormalities have also been linked to maternal hypoxia caused by maternal smoking, with the estimated attributable fraction of orofacial clefts due to smoking in early pregnancy being 6.1%.

• #26 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.

• #27 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.

• #28 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.

• #29 Cleft Palate – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563128/

  A child of an affected parent has a 3% to 4% risk of CL/P and about 6% of CPO. […] Approximately 50% of CPO cases are associated with other congenital anomalies, more frequent than CL/P, which is associated with a congenital syndrome in about 15% of cases. […] The most commonly discussed are CHARGE (coloboma, heart defects, atresia choanae, growth retardation, genital abnormalities, and ear abnormalities) syndrome and velocardiofacial or DiGeorge syndrome (22q11.2 deletion). […] A clear environmental impact on the development of CL/P and CPO has been shown. […] Risk factors for malformation include smoking, diabetes, gestational diabetes, and teratogen exposure (eg, valproic acid, phenytoin, retinoic acid, dioxin, and thalidomide).

• #30 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.

• #31

  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.

• #32 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/

  Just like most sisters, Tristyn and Raigyn Snyder will share toys, clothes and friends throughout their lives. They also share something unique: a genetic condition called Van der Woude syndrome. […] When Cindy Snyder was 12 weeks pregnant with Tristyn, a prenatal ultrasound showed that the baby had a bilateral cleft lip and palate. […] Van der Woude syndrome is the most common single-cause of cleft lip and palate. Individuals with VWS may have a cleft lip with or without a cleft palate, a submucous cleft palate, lip pits along the lower lip, or any combination of these features. […] “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. […] The Snyders were prepared when Raigyn was born with a bilateral cleft lip and palate.

• #33 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.

• #34 Cleft Palate – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563128/

  A child of an affected parent has a 3% to 4% risk of CL/P and about 6% of CPO. […] Approximately 50% of CPO cases are associated with other congenital anomalies, more frequent than CL/P, which is associated with a congenital syndrome in about 15% of cases. […] The most commonly discussed are CHARGE (coloboma, heart defects, atresia choanae, growth retardation, genital abnormalities, and ear abnormalities) syndrome and velocardiofacial or DiGeorge syndrome (22q11.2 deletion). […] A clear environmental impact on the development of CL/P and CPO has been shown. […] Risk factors for malformation include smoking, diabetes, gestational diabetes, and teratogen exposure (eg, valproic acid, phenytoin, retinoic acid, dioxin, and thalidomide).

• #35 Cleft Palate – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563128/

  A child of an affected parent has a 3% to 4% risk of CL/P and about 6% of CPO. […] Approximately 50% of CPO cases are associated with other congenital anomalies, more frequent than CL/P, which is associated with a congenital syndrome in about 15% of cases. […] The most commonly discussed are CHARGE (coloboma, heart defects, atresia choanae, growth retardation, genital abnormalities, and ear abnormalities) syndrome and velocardiofacial or DiGeorge syndrome (22q11.2 deletion). […] A clear environmental impact on the development of CL/P and CPO has been shown. […] Risk factors for malformation include smoking, diabetes, gestational diabetes, and teratogen exposure (eg, valproic acid, phenytoin, retinoic acid, dioxin, and thalidomide).

• #36 Cleft Lip and Cleft Palate – Seattle Children’s

  https://www.seattlechildrens.org/conditions/cleft-lip-palate/

  Cleft lip and cleft palate happen when part of the lip or roof of the mouth (palate) does not form properly. This leaves a gap (cleft). These birth defects happen in early pregnancy. […] Most (60%) cleft lips and palates are not linked with anything that happens during or after pregnancy. A few of the exceptions are: Exposure to the drug phenytoin (Dilantin) during pregnancy: makes cleft lip 10 times more likely. Smoking while pregnant: makes cleft lip 2 times more likely. Use of alcohol, antiseizure medicine or vitamin A (retinoic acid): linked with birth defects that include cleft lip and palate. […] Genetic syndromes that cause clefting. Clefting is sometimes part of a syndrome caused by changes in genes. Children with these syndromes also have other medical problems. More than 40% of children who have cleft palate but without cleft lip have conditions such as van der Woude syndrome, 22q11.2-related disorders, Robin sequence, Stickler syndrome and Treacher Collins syndrome. […] There is a greater chance of having a child with clefting if a parent or sibling has one. Your doctor or counselors at our Craniofacial Genetics Clinic can talk with you about the chance for your family.

• #37 Cleft lip and cleft palate – Wikipedia

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

  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. […] 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 lysine demethylase, and is involved in epigenetic regulation. […] Cleft lip and other congenital abnormalities have also been linked to maternal hypoxia caused by maternal smoking, with the estimated attributable fraction of orofacial clefts due to smoking in early pregnancy being 6.1%.

• #38 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. […] Maternal hypoxia due to smoking by pregnant women may also lead to cleft lip. In 6.1% of cases, children were found to born with cleft lip and palate with women smoking during pregnancy. One important point to note here is that cleft lip and palate occur in very early pregnancy, so, stopping smoking after diagnosis of pregnancy may not reduce the incidence of these clefts. Alcohol intake during pregnancy has also been attributed to cleft lip and palate as alcohol influences the development of cranial neural crest cells. But degree of influence of alcohol on neural crest cells is unknown and requires further research. There is evidence of causing cleft lip and palate in children of women who received anti-hypertensive treatment during pregnancy. Various other factors causing cleft lip and palate include pesticide exposure, maternal diet, retinoid intake, anticonvulsant drugs like nitrate compounds, organic solvents, parental exposure to lead, alcohol, cigarette use and intake of psychoactive drugs such as cocaine, crack cocaine and heroin.

• #39 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. […] Maternal hypoxia due to smoking by pregnant women may also lead to cleft lip. In 6.1% of cases, children were found to born with cleft lip and palate with women smoking during pregnancy. One important point to note here is that cleft lip and palate occur in very early pregnancy, so, stopping smoking after diagnosis of pregnancy may not reduce the incidence of these clefts. Alcohol intake during pregnancy has also been attributed to cleft lip and palate as alcohol influences the development of cranial neural crest cells. But degree of influence of alcohol on neural crest cells is unknown and requires further research. There is evidence of causing cleft lip and palate in children of women who received anti-hypertensive treatment during pregnancy. Various other factors causing cleft lip and palate include pesticide exposure, maternal diet, retinoid intake, anticonvulsant drugs like nitrate compounds, organic solvents, parental exposure to lead, alcohol, cigarette use and intake of psychoactive drugs such as cocaine, crack cocaine and heroin.

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

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

  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.

• #41 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. […] Maternal hypoxia due to smoking by pregnant women may also lead to cleft lip. In 6.1% of cases, children were found to born with cleft lip and palate with women smoking during pregnancy. One important point to note here is that cleft lip and palate occur in very early pregnancy, so, stopping smoking after diagnosis of pregnancy may not reduce the incidence of these clefts. Alcohol intake during pregnancy has also been attributed to cleft lip and palate as alcohol influences the development of cranial neural crest cells. But degree of influence of alcohol on neural crest cells is unknown and requires further research. There is evidence of causing cleft lip and palate in children of women who received anti-hypertensive treatment during pregnancy. Various other factors causing cleft lip and palate include pesticide exposure, maternal diet, retinoid intake, anticonvulsant drugs like nitrate compounds, organic solvents, parental exposure to lead, alcohol, cigarette use and intake of psychoactive drugs such as cocaine, crack cocaine and heroin.

• #42 Cleft Lip and Palate: Causes, Symptoms, Diagnosis, Treatment

  https://www.webmd.com/oral-health/cleft-lip-cleft-palate

  Another potential cause may be related to a medication a mother may have taken during pregnancy. Some drugs that may cause cleft lip and cleft palate include anti-seizure/anticonvulsant drugs, acne drugs containing Accutane, and methotrexate, a drug commonly used for treating cancer, arthritis, and psoriasis. […] Cleft lip and cleft palate may also occur as a result of exposure to viruses or chemicals while the fetus is developing in the womb. […] In other situations, cleft lip and cleft palate may be part of another medical condition.

• #43 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.

• #44 The Causes of Cleft Lip and/or Palate – myFace

  https://www.myface.org/craniofacial-conditions/cleft-lip-and-or-palate/causes/

  The exact cause of cleft lip and palate is unknown, but nonsyndromic cases of cleft lip/palate may be due to either genetic or environmental factors. […] Over 30 gene mutations have been identified as being linked to cleft lip and palate, and parents with a family history of clefts have a higher risk of having a child with a cleft: […] There are also many environmental factors that have been associated with increased risk of cleft lip and palate, including: […] Exposure to various drugs (anti-seizure medications, ondansetron, diazepam, nitrofurantoin, corticosteroids, methotrexate) during pregnancy […] Maternal tobacco or alcohol use […] Maternal folate deficiency during pregnancy […] Maternal obesity […] Amniotic band sequence […] Maternal diabetes.

• #45 Cleft Palate – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563128/

  A child of an affected parent has a 3% to 4% risk of CL/P and about 6% of CPO. […] Approximately 50% of CPO cases are associated with other congenital anomalies, more frequent than CL/P, which is associated with a congenital syndrome in about 15% of cases. […] The most commonly discussed are CHARGE (coloboma, heart defects, atresia choanae, growth retardation, genital abnormalities, and ear abnormalities) syndrome and velocardiofacial or DiGeorge syndrome (22q11.2 deletion). […] A clear environmental impact on the development of CL/P and CPO has been shown. […] Risk factors for malformation include smoking, diabetes, gestational diabetes, and teratogen exposure (eg, valproic acid, phenytoin, retinoic acid, dioxin, and thalidomide).

• #46 Unraveling the Heartfelt Causes of Cleft Lip and Palate

  https://www.smbalaji.com/causes-of-cleft-lip-and-palate/

  Deficiencies in folic acid, iron, iodine, and zinc during pregnancy have also been associated with cleft lip and palate. […] Exposure to viruses, infectious diseases, harmful chemicals, vapors, pesticides, gunpowder fumes, nuclear radiation, X-rays, gamma rays, or dangerous reagents in industrial workplaces can all increase the risk of cleft lip and palate.

• #47 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.

• #48 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.

• #49 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. […] The failure of development of the upper lip and palate occurs early in pregnancy, between the fifth and ninth weeks. […] 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.

• #50

  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.

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

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

  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.

• #52 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.

• #53 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 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. […] 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.

• #54 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. […] 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.

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

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

  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.

• #56 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.

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

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

  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 arent readily apparent. Genetic testing can help determine if a childs cleft is part of an underlying condition.

• #58 Cleft Lip and Cleft Palate: Causes, Treatment Plans & Surgical Repair | Nationwide Children’s Hospital

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

  Cleft lip and/or palate is the most common birth defect in the United States, affecting one of every 700 babies born. That 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. 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. […] Although cleft lip with or without cleft palate can occur in any race, there is a higher incidence in people of Asian, Native American or Hispanic descent. There is a lower incidence in African-American individuals.

• #59 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. When a child has a cleft but neither biological parent does, theres a 2- to 8-percent chance that biological siblings of the child will also have clefts. When a parent and a biological child both have clefts, the chances are even greater that the parents future children will have clefts.

• #60 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Causes-of-cleft-lip-and-palate.aspx

  Environmental causes include poor early pregnancy health and exposure to various toxins during pregnancy. Exposure to alcohol and tobacco are linked to risk of babies born with cleft lip and/or palate. […] Deficiency of B vitamins and folic acid in maternal diet is another commonly associated cause of cleft lip and palate in the new born. […] Parents who are older than usual at the time of birth of their baby are at higher risk of having children with cleft lip and or palate. […] A viral infection during pregnancy may also be associated with cleft lip and palate. Mothers who are obese have a higher chance of their child being born with a cleft.

• #61 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.

• #62 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 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. […] 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.

• #63 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.

• #64 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

  Various genes have been identified with mutations that can cause clefts, showing a connection between the type of mutation and the resulting phenotype. […] Most research points to a blend of genetic and environmental factors behind cleft formation, with multiple genes identified for non-syndromic cleft lip and palate. […] Stress elevates maternal and fetal cortisol levels, known for their teratogenic effects, by downregulating the enzyme 11-beta-hydroxysteroid dehydrogenase type 2 (11beta HSD2), crucial for regulating the placental barrier. […] 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. […] 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.

• #65 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.

• #66 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 other—for 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 location—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. […] Zucchero et al reported that variants of IRF6 may be responsible for 12% of nonsyndromic cleft lip and palate, suggesting that this gene would play a substantial role in the causation of orofacial clefts. […] The identification of factors that contribute to the etiology of nonsyndromic CL/P is important for prevention, treatment planning, and education.

• #67 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.

• #68 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 6. […] 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 bilateral cleft lip and palate, there is a premaxillary protrusion that is typically seen as a paranasal echogenic mass. The premaxillary protrusion results from instability of the facial structures during embryologic development, which produces uninhibited growth of the vomer and premaxillary bones and soft tissues.

• #69 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/

  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.

• #70 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 6. […] 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 bilateral cleft lip and palate, there is a premaxillary protrusion that is typically seen as a paranasal echogenic mass. The premaxillary protrusion results from instability of the facial structures during embryologic development, which produces uninhibited growth of the vomer and premaxillary bones and soft tissues.

• #71 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.

• #72 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.

• #73 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.

• #74 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.

• #75 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 other—for 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 location—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. […] Zucchero et al reported that variants of IRF6 may be responsible for 12% of nonsyndromic cleft lip and palate, suggesting that this gene would play a substantial role in the causation of orofacial clefts. […] The identification of factors that contribute to the etiology of nonsyndromic CL/P is important for prevention, treatment planning, and education.

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