Assisted reproductive technology (ART) is a general term referring to methods used to achieve pregnancy by artificial or partially artificial means. According to the CDC, in general, ART procedures involve surgically removing eggs from a woman's ovaries, combining them with sperm in the laboratory, and returning them to the woman's body or donating them to another woman. ART has been associated with epigenetic syndromes, specifically BWS and Angelman syndrome. Three groups have shown an increased rate of ART conception in children with BWS. A retrospective case control study from Australia found a 1 in 4000 risk of BWS in their in-vitro population, several times higher than the general population. Another study found that children conceived by in vitro fertilisation (IVF) are three to four times more likely to develop the condition. No specific type of ART has been more closely associated with BWS. The mechanism by which ART produces this effect is still under investigation.

Genetic counseling for VWS involves discussion of disease transmission in the autosomal dominant manner and possibilities for penetrance and expression in offspring. Autosomal dominance means affected parents have a 50% chance of passing on their mutated "IRF6" allele to a their child. Furthermore, if a cleft patient has lip pits, he or she has a ten times greater risk of having a child with cleft lip with or without cleft palate than a cleft patient who does not have lip pits. Types of clefting between parents and affected children are significantly associated; however, different types of clefts may occur horizontally and vertically within the same pedigree. In cases where clefting is the only symptom, a complete family history must be taken to ensure the patient does not have non-syndromic clefting.

The prevalence has been estimated at 1 in 10,000 births, but exact values are hard to know because some that have the symptoms rarely have Pierre-Robin sequence (without any other associated malformation).

Environmental influences may also cause, or interact with genetics to produce, orofacial clefting. An example of how environmental factors might be linked to genetics comes from research on mutations in the gene "PHF8" that cause cleft lip/palate (see above). It was found that PHF8 encodes for a histone lysine demethylase, and is involved in epigenetic regulation. The catalytic activity of PHF8 depends on molecular oxygen, a fact considered important with respect to reports on increased incidence of cleft lip/palate in mice that have been exposed to hypoxia early during pregnancy. In humans, fetal cleft lip and other congenital abnormalities have also been linked to maternal hypoxia, as caused by e.g. maternal smoking, maternal alcohol abuse or some forms of maternal hypertension treatment. Other environmental factors that have been studied include: seasonal causes (such as pesticide exposure); maternal diet and vitamin intake; retinoids — which are members of the vitamin A family; anticonvulsant drugs; nitrate compounds; organic solvents; parental exposure to lead; alcohol; cigarette use; and a number of other psychoactive drugs (e.g. cocaine, crack cocaine, heroin).

Current research continues to investigate the extent to which folic acid can reduce the incidence of clefting.

Beckwith–Wiedemann syndrome has an estimated incidence of one in 13,700; about 300 children with BWS are born each year in the United States. The exact incidence of BWS is unknown because of the marked variability in the syndrome's presentation and difficulties with diagnosis. The number of reported infants born with BWS is most likely low because many are born with BWS, but have clinical features that are less prominent and therefore missed. BWS has been documented in a variety of ethnic groups and occurs equally in males and females.

Children conceived through In vitro fertilization have a three to fourfold increased chance of developing Beckwith–Wiedemann syndrome. It is thought that this is due to genes being turned on or off by the IVF procedures.

Lip pits may be surgically removed either for aesthetic reasons or discomfort due to inflammation caused by bacterial infections or chronic saliva excretion, though spontaneous shrinkage of the lip pits has occurred in some rare cases. Chronic inflammation has also been reported to cause squamous-cell carcinoma. It is essential to completely remove the entire lip pit canal, as mucoid cysts can develop if mucous glands are not removed. A possible side effect of removing the lip pits is a loose lip muscle. Other conditions associated with VWS, including CL, CP, congenital heart defects, etc. are surgically corrected or otherwise treated as they would be if they were non-syndromic.

In a newborn boy thought to have Fryns syndrome, Clark and Fenner-Gonzales (1989) found mosaicism for a tandem duplication of 1q24-q31.2. They suggested that the gene for this disorder is located in that region. However, de Jong et al. (1989), Krassikoff and Sekhon (1990), and Dean et al. (1991) found possible Fryns syndrome associated with anomalies of chromosome 15, chromosome 6, chromosome 8(human)and chromosome 22, respectively. Thus, these cases may all represent mimics of the mendelian syndrome and have no significance as to the location of the gene for the recessive disorder.

By array CGH, Slavotinek et al. (2005) screened patients with DIH and additional phenotypic anomalies consistent with Fryns syndrome for cryptic chromosomal aberrations. They identified submicroscopic chromosome deletions in 3 probands who had previously been diagnosed with Fryns syndrome and had normal karyotyping with G-banded chromosome analysis. Two female infants were found to have microdeletions involving 15q26.2 (see 142340), and 1 male infant had a deletion in band 8p23.1 (see 222400).

The inheritance of Impossible syndrome is suspected to be autosomal recessive, which means the affected gene is located on an autosome, and two copies of the gene - one from each parent - are required to have an infant with the disorder.

There is still some discussion on whether FND is sporadic or genetic. The majority of FND cases are sporadic. Yet, some studies describe families with multiple members with FND. Gene mutations are likely to play an important role in the cause. Unfortunately, the genetic cause for most types of FND remains undetermined.

Frontonasal dysplasia (FND) is a congenital malformation of the midface.

For the diagnosis of FND, a patient should present at least two of the following characteristics: hypertelorism (an increased distance between the eyes), a wide nasal root, vertical midline cleft of the nose and/or upper lip, cleft of the wings of the nose, malformed nasal tip, encephalocele (an opening of the skull with protrusion of the brain) or V-shaped hair pattern on the forehead.

The cause of FND remains unknown. FND seems to be sporadic (random) and multiple environmental factors are suggested as possible causes for the syndrome. However, in some families multiple cases of FND were reported, which suggests a genetic cause of FND.

Cleft lip and palate occurs in about 1 to 2 per 1000 births in the developed world.

Rates for cleft lip with or without cleft palate and cleft palate alone varies within different ethnic groups.

The highest prevalence rates for (CL ± P) are reported for Native Americans and Asians. Africans have the lowest prevalence rates.

- Native Americans: 3.74/1000

- Japanese: 0.82/1000 to 3.36/1000

- Chinese: 1.45/1000 to 4.04/1000

- Caucasians: 1.43/1000 to 1.86/1000

- Latin Americans: 1.04/1000

- Africans: 0.18/1000 to 1.67/1000

Rate of occurrence of CPO is similar for Caucasians, Africans, North American natives, Japanese and Chinese. The trait is dominant.

It caused about 4,000 deaths globally in 2010 down from 8,400 in 1990.

Prevalence of "cleft uvula" has varied from .02% to 18.8% with the highest numbers found among Chippewa and Navajo and the lowest generally in Africans.

It is not known how this abnormality occurs in infants, but one theory is that, at some time during the stage of the formation of the bones of the fetus, the tip of the jaw (mandible) becomes 'stuck' in the point where each of the collar bones (clavicle) meet (the sternum), effectively preventing the jaw bones from growing. It is thought that, at about 12 to 14 weeks gestation, when the fetus begins to move, the movement of the head causes the jaw to "pop out' of the collar bones. From this time on, the jaw of the fetus grows as it would normally, with the result that, when born, the jaw of the baby is much smaller (micrognathia) than it would have been with normal development, although it does continue to grow at a normal rate until the child reaches maturity.

However, association with gene loci 2q24.1-33.3, 4q32-qter, 11q21-23.1, and 17q21-24.3 has been found. Recent studies have indicated that genetic dysregulation of SOX9 gene prevents the SOX9 protein from properly controlling the development of facial structures, which leads to isolated PRS. Similarly, KCNJ2 gene also has a role to play. Overlap with certain other genetic syndromes like Patau syndrome has also been found.

PRS may occur in isolation, but it is often part of an underlying disorder or syndrome. The most common is Stickler Syndrome. Other disorders causing PRS, according to Dr. Robert J. Sphrintzen Ph.D. of the Center for Craniofacial Disorders Montefiore Medical Center, are Velocardiofacial syndrome, Fetal Alcohol Syndrome and Treacher Collins Syndrome. For more disorders associated with PRS see Dr. Sphrintzen's article entitled "The Implications of the Diagnosis of Robin Sequence".

Glossoptosis is a medical condition and abnormality which involves the downward displacement or retraction of the tongue. It may cause non-fusion of the hard palate causing cleft palate.

It is one of the features of Pierre Robin sequence and Down syndrome.

Opitz G/BBB Syndrome is a rare genetic condition caused by one of two major types of mutations: MID1 mutation on the short (p) arm of the X chromosome or a mutation of the 22q11.2 gene on the 22nd chromosome. Since it is a genetic disease, it is an inherited condition. However, there is an extremely wide variability in how the disease presents itself.

In terms of prevention, several researchers strongly suggest prenatal testing for at-risk pregnancies if a MID1 mutation has been identified in a family member. Doctors can perform a fetal sex test through chromosome analysis and then screen the DNA for any mutations causing the disease. Knowing that a child may be born with Opitz G/BBB syndrome could help physicians prepare for the child’s needs and the family prepare emotionally. Furthermore, genetic counseling for young adults that are affected, are carriers or are at risk of carrying is strongly suggested, as well (Meroni, Opitz G/BBB syndrome, 2012). Current research suggests that the cause is genetic and no known environmental risk factors have been documented. The only education for prevention suggested is genetic testing for at-risk young adults when a mutation is found or suspected in a family member.

In France, Aymé, "et al." (1989) estimated the prevalence of Fryns syndrome to be 0.7 per 10,000 births based on the diagnosis of 6 cases in a series of 112,276 consecutive births (live births and perinatal deaths).

TCS occurs in about one in 50,000 births in Europe. Worldwide, it is estimated to occur in one in 10,000 to one in 50,000 births.

Impossible Syndrome, or Chondrodysplasia situs inversus imperforate anus polydactyly, is a complex combination of human congenital malformations (birth defects).

The malformations include chondrodysplasia (improper growth of bone and cartilage), situs inversus totalis (chest and abdominal organs all a mirror image of normal), cleft larynx and epiglottis, hexadactyly (six digits) on hands and feet, diaphragmatic hernia, pancreatic abnormalities, kidney abnormal on one side and absent on the other side, micropenis and ambiguous genitalia, and imperforate anus.

Only one case of Impossible Syndrome has been reported; the infant was premature and stillborn.

The condition develops in the fetus at approximately 4 weeks gestational age, when some form of vascular problem such as blood clotting leads to insufficient blood supply to the face. This can be caused by physical trauma, though there is some evidence of it being hereditary . This restricts the developmental ability of that area of the face. Currently there are no definitive reasons for the development of the condition.

The disorder can be associated with a number of psychological symptoms, anxiety, depression, social phobia, body image disorders, and patients may be subjected to discrimination, bullying and name calling especially when young. A multi-disciplinary team and parental support should include these issues.

The prognosis depends on the location and severity of the constricting bands. Every case is different and multiple bands may be entangled around the fetus.

Bands which wrap around fingers and toes can result in syndactyly or amputations of the digits. In other instances, bands can wrap around limbs causing restriction of movement resulting in clubbed feet. In more severe cases, the bands can constrict the limb causing decreased blood supply and amputation. Amniotic bands can also sometimes attach to the face or neck causing deformities such as cleft lip and palate. If the bands become wrapped around the head or umbilical cord it can be life-threatening for the fetus.

The number of cases of miscarriage that can be attributed to ABS is unknown, although it has been reported that it may be the cause of 178 in 10,000 miscarriages.

Minor physical anomalies (MPAs) are relatively minor (typically painless and, in themselves, harmless) congenital physical abnormalities consisting of features such as low-set ears, single transverse palmar crease, telecanthus, micrognathism, macrocephaly, hypotonia and furrowed tongue. While MPAs may have a genetic basis, they might also be caused by factors in the fetal environment: anoxia, bleeding, or infection. MPAs have been linked to disorders of pregnancy and are thought by some to be a marker for insults to the fetal neural development towards the end of the first trimester. Thus, in the neurodevelopmental literature, they are seen as indirect indications of inferferences with brain development.

MPAs have been studied in autism, Down syndrome, and in schizophrenia. A 2008 meta-analysis found that MPAs are significantly increased in the autistic population. A 1998 study found that 60% of its schizophrenic sample and 38% of their siblings had 6 or more MPAs (especially in the craniofacial area), while only 5% of the control group showed that many.

The most often cited MPA, high arched palate, is described in articles as a microform of a cleft palate. Cleft palates are partly attributable to hypoxia. The vaulted palate caused by nasal obstruction and consequent mouth breathing, without the lateralising effect of the tongue, can produce hypoxia at night.

Other MPAs are reported only sporadically. Capillary malformation is induced by RASA1 mutation and can be changed by hypoxia. A study in the American Journal of Psychiatry by Trixler et al.: found hemangiomas to be highly significant in schizophrenia. Exotropia is reported as having low correlation and high significance as well. It can be caused by perinatal hypoxia.

Amniotic banding affects approximately 1 in 1,200 live births. It is also believed to be the cause of 178 in 10,000 miscarriages. Up to 50% of cases have other congenital anomalies including cleft lip, cleft palate, and clubfoot deformity. Hand and finger anomalies occur in up to 80%.

Roberts syndrome is an extremely rare condition that only affects about 150 reported individuals. Although there have been only about 150 reported cases, the affected group is quite diverse and spread worldwide. Parental consanguinity (parents are closely related) is common with this genetic disorder. The frequency of Roberts syndrome carriers is unknown.

Hemifacial microsomia (HFM) is a congenital disorder that affects the development of the lower half of the face, most commonly the ears, the mouth and the mandible. It usually occurs on one side of the face, but both sides are sometimes affected. If severe, it may result in difficulties in breathing due to obstruction of the trachea—sometimes even requiring a tracheotomy. With an incidence in the range of 1:3500 to 1:4500, it is the second most common birth defect of the face, after cleft lip and cleft palate. HFM shares many similarities with Treacher Collins syndrome.

Yim–Ebbin syndrome is a congenital disorder characterized by the absence of arms, a cleft lip and palate, hydrocephalus, and an iris coloboma. It was first described by Yim and Ebbin in 1982, and later by Thomas and Donnai in 1994. In 1996, a third case was reported by Froster et al. who suggested that the three cases were related and represented a distinct syndrome. In 2000, a similar case was reported by Pierri et al.

It is also known as "amelia cleft lip palate hydrocephalus iris coloboma".