The reported incidence of constriction ring syndrome varies from 1/1200 and 1/15000 live births. The prevalence is equally in male and female.

Fetomaternal factors like prematurity, maternal illnes, low birth weight and maternal drug exposure are predisposing factors for the constriction ring syndrome.

No positive relationship between CRS and genetic inheritance has been reported.

Hand-foot-genital syndrome is inherited in an autosomal dominant manner. The proportion of cases caused by de novo mutations is unknown because of the small number of individuals described. If a parent of the proband is affected, the risk to the siblings is 50%. When the parents are clinically unaffected, the risk to the sibs of a proband appears to be low. Each child of an individual with HFGS has a 50% chance of inheriting the mutation. Prenatal testing may be available through laboratories offering custom prenatal testing for families in which the disease-causing mutation has been identified in an affected family member.

Patients with abnormal cardiac and kidney function may be more at risk for hemolytic uremic syndrome

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.

There has been a great deal of research to understand the cause of PHACE Syndrome. The abnormalities associated with this syndrome are thought to be due to errors that occur very early during development. Unfortunately, why the errors occur, or the exact cause is still unknown. PHACE has a shared biology of other vascular anomalies. There may be a genetic component involved and studies are underway to investigate this idea. No familial cases have been identified to date. Research is ongoing to find the cause of all vascular anomalies including PHACE Syndrome.

The incidence of VACTERL association is estimated to be approximately 1 in 10,000 to 1 in 40,000 live-born infants. It is seen more frequently in infants born to diabetic mothers. While most cases are sporadic, there are clearly families who present with multiple involved members.

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.

In some cases, the defect is linked to mutations of the EMX2, SIX3, and Collagen, type IV, alpha 1 genes. Because having a sibling with schizencephaly has been statistically shown to increase risk of the disorder, it is possible that there is a heritable genetic component to the disease.

The syndromes associated with central polydactyly are:

Bardet–Biedl syndrome,

Meckel syndrome,

Pallister–Hall syndrome,

Legius syndrome,

Holt–Oram syndrome,

Also, central polydactyly can be associated with syndactyly and cleft hand.

Other syndromes including polydactyly include acrocallosal syndrome, basal cell nevus syndrome, Biemond syndrome, ectrodactyly-ectodermal dysplasias-cleft lip/palate syndrome, mirror hand deformity, Mohr syndrome, oral-facial-digital syndrome, Rubinstein-Taybi syndrome, short rib polydactyly, and VATER association.

It can also occur with a triphalangeal thumb.

Type VII of radial polydactyly is associated with several syndromes:

Holt–Oram syndrome, Fanconi anemia (aplastic anemia by the age of 6), Townes–Brocks syndrome, and Greig cephalopolysyndactyly (also known to occur with ulnar polydactyly).

Ectrodactyly can be caused by various changes to 7q. When 7q is altered by a deletion or a translocation ectrodactyly can sometimes be associated with hearing loss. Ectrodactyly, or Split hand/split foot malformation (SHFM) type 1 is the only form of split hand/ malformation associated with sensorineural hearing loss.

Because the cause of facial clefts still is unclear, it is difficult to say what may prevent children being born with facial clefts. It seems that folic acid contributes to lowering the risk of a child being born with a facial cleft.

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.

A large number of human gene defects can cause ectrodactyly. The most common mode of inheritance is autosomal dominant with reduced penetrance, while autosomal recessive and X-linked forms occur more rarely. Ectrodactyly can also be caused by a duplication on 10q24. Detailed studies of a number of mouse models for ectrodactyly have also revealed that a failure to maintain median apical ectodermal ridge (AER) signalling can be the main pathogenic mechanism in triggering this abnormality.

A number of factors make the identification of the genetic defects underlying human ectrodactyly a complicated process: the limited number of families linked to each split hand/foot malformation (SHFM) locus, the large number of morphogens involved in limb development, the complex interactions between these morphogens, the involvement of modifier genes, and the presumed involvement of multiple gene or long-range regulatory elements in some cases of ectrodactyly. In the clinical setting these genetic characteristics can become problematic and making predictions of carrier status and severity of the disease impossible to predict.

In 2011, a novel mutation in DLX5 was found to be involved in SHFM.

Ectrodactyly is frequently seen with other congenital anomalies. Syndromes in which ectrodactyly is associated with other abnormalities can occur when two or more genes are affected by a chromosomal rearrangement. Disorders associated with ectrodactyly include Ectrodactyly-Ectodermal Dysplasia-Clefting (EEC) syndrome, which is closely correlated to the ADULT syndrome and Limb-mammary (LMS) syndrome, Ectrodactyly-Cleft Palate (ECP) syndrome, Ectrodactyly-Ectodermal Dysplasia-Macular Dystrophy syndrome, Ectrodactyly-Fibular Aplasia/Hypoplasia (EFA) syndrome, and Ectrodactyly-Polydactyly. More than 50 syndromes and associations involving ectrodactyly are distinguished in the London Dysmorphology Database.

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.

OAFNS is a combination of FND and oculo-auriculo-vertebral spectrum (OAVS).

The diagnosis of OAVS is based on the following facial characteristics: microtia (underdeveloped external ear), preauricular tags, facial asymmetry, mandibular hypoplasia and epibulbar lipodermoids (benign tumor of the eye which consists of adipose and fibrous tissue).

There still remains discussion about the classification and the minimal amount of characteristics. When someone presents with FND and the characteristics of OAVS, the diagnosis OAFNS may be made.

As the incidence of OAFNS is unknown, there are probably a lot of children with mild phenotypes that aren’t being diagnosed as being OAFNS.

The cause of OAFNS is unknown, but there are some theories about the genesis. Autosomal recessive inheritance is suggested because of a case with two affected siblings and a case with consanguineous parents. However, another study shows that it is more plausible that OAFNS is sporadic.

It is known that maternal diabetes plays a role in developing malformations of craniofacial structures and in OAVS. Therefore, it is suggested as a cause of OAFNS. Folate deficiency is also suggested as possible mechanism.

Low-dose CT protocols should be considered in diagnosing children with OAFNS.

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.

Diagnosis is based on physical examination including radiographs of the hands and feet and imaging studies of the kidneys, bladder, and female reproductive tract. HOXA13 is the only gene known to be associated with HFGS. Approximately 60% of mutations are polyalanine expansions. Molecular genetic testing is clinically available.

A low socioeconomic status in a deprived neighborhood may include exposure to “environmental stressors and risk factors.” Socioeconomic inequalities are commonly measured by the Cartairs-Morris score, Index of Multiple Deprivation, Townsend deprivation index, and the Jarman score. The Jarman score, for example, considers “unemployment, overcrowding, single parents, under-fives, elderly living alone, ethnicity, low social class and residential mobility.” In Vos’ meta-analysis these indices are used to view the effect of low SES neighborhoods on maternal health. In the meta-analysis, data from individual studies were collected from 1985 up until 2008. Vos concludes that a correlation exists between prenatal adversities and deprived neighborhoods. Other studies have shown that low SES is closely associated with the development of the fetus in utero and growth retardation. Studies also suggest that children born in low SES families are “likely to be born prematurely, at low birth weight, or with asphyxia, a birth defect, a disability, fetal alcohol syndrome, or AIDS.” Bradley and Corwyn also suggest that congenital disorders arise from the mother’s lack of nutrition, a poor lifestyle, maternal substance abuse and “living in a neighborhood that contains hazards affecting fetal development (toxic waste dumps).” In a meta-analysis that viewed how inequalities influenced maternal health, it was suggested that deprived neighborhoods often promoted behaviors such as smoking, drug and alcohol use. After controlling for socioeconomic factors and ethnicity, several individual studies demonstrated an association with outcomes such as perinatal mortality and preterm birth.

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.

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.

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.

There are three different theories to the cause of the constriction ring syndrome.

The first is the intrinsic theory, which was proposed by Streeter in 1930, implicates an anomaly in germ plasm resulting in the defects. This theory is reinforced by the clinical presentation of the constriction rings with other internal visceral and systematic anomalies. Because of these other anomalies the names “Constriction Ring Syndrome”, “Constriction Band Syndrome” and “Streeter Bands” are given to this defect/disease.

The second theory postulates the involvement of an intrauterine disruption during pregnancy followed by a cascade of events involving amniotic rupture. When spontaneous rupture of the amnion occurs early in the second trimester, the separation of amnion from chorion produces many small, thin strands that can become entangled within digits and toes.

The names “Amniotic Band Syndrome”, “Amniotic Disruption Complex", "Amniochorionic Mesoblastic Fibrous Strings", are based on this theory.

The third theory postulates the involvement of intrauterine trauma. Intrauterine trauma could be something like amniocentesis, or something like an fetal surgery. An intrauterine trauma could result in hemorrhage leading to acrosyndactyly. One study also showed the presence of bands as confirmed by sonography after fetal surgery.

Because of these different theories, there are many names for this syndrome. For a long time people believed the second theory about the amniotic rupture and strands. In the research cases not every child had a real (amniotic) strand. It could be that there has to be another explanation for the development of these anomalies.

The condition is also known by various other names:

- Lateral facial dysplasia

- First and second branchial arch syndrome

- Oral-mandibular-auricular syndrome

- Otomandibular dysostosis

- Craniofacial microsomia

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).