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.

The effects of paternal age on offspring are not yet well understood and are studied far less extensively than the effects of maternal age. Fathers contribute proportionally more DNA mutations to their offspring via their germ cells than the mother, with the paternal age governing how many mutations are passed on. This is because, as humans age, male germ cells acquire mutations at a much faster rate than female germ cells.

Around a 5% increase in the incidence of ventricular septal defects, atrial septal defects, and patent ductus arteriosus in offspring has been found to be correlated with advanced paternal age. Advanced paternal age has also been linked to increased risk of achondroplasia and Apert syndrome. Offspring born to fathers under the age of 20 show increased risk of being affected by patent ductus arteriosus, ventricular septal defects, and the tetralogy of Fallot. It is hypothesized that this may be due to environmental exposures or lifestyle choices.

Research has found that there is a correlation between advanced paternal age and risk of birth defects such as limb anomalies, syndromes involving multiple systems, and Down's syndrome. Recent studies have concluded that 5-9% of Down's syndrome cases are due to paternal effects, but these findings are controversial.

There is concrete evidence that advanced paternal age is associated with the increased likelihood that a mother will suffer from a miscarriage or that fetal death will occur.

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.

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.

Treatment is symptomatic, often addressing indicators associated with peripheral pulmonary artery stenosis. Laryngotracheal calcification resulting in dyspnea and forceful breathing can be treated with bronchodilators including the short and long-acting β2-agonists, and various anticholinergics. Prognosis is good, yet life expectancy depends on the severity and extent of diffuse pulmonary and arterial calcification.

Möbius syndrome results from the underdevelopment of the VI and VII cranial nerves. The VI cranial nerve controls lateral eye movement, and the VII cranial nerve controls facial expression.

The causes of Möbius syndrome are poorly understood. Möbius syndrome is thought to result from a vascular disruption (temporary loss of bloodflow) in the brain during prenatal development. There could be many reasons that a vascular disruption leading to Möbius syndrome might occur. Most cases do not appear to be genetic. However, genetic links have been found in a few families. Some maternal trauma may result in impaired or interrupted blood flow (ischemia) or lack of oxygen (hypoxia) to a developing fetus. Some cases are associated with reciprocal translocation between chromosomes or maternal illness. In the majority of cases of Möbius syndrome in which autosomal dominant inheritance is suspected, sixth and seventh cranial nerve paralysis (palsy) occurs without associated limb abnormalities.

The use of drugs and a traumatic pregnancy may also be linked to the development of Möbius syndrome. The use of the drugs misoprostol or thalidomide by women during pregnancy has been linked to the development of Möbius syndrome in some cases. Misoprostol is used to induce abortions in Brazil and Argentina as well as in the United States. Misoprostol abortions are successful 90% of the time, meaning that 10% of the time the pregnancy continues. Studies show that the use of misoprostal during pregnancy increases the risk of developing Möbius syndrome by a factor of 30. While this is a dramatic increase in risk, the incidence of Möbius syndrome without misoprostal use is estimated at one in 50000 to 100000 births (making the incidence of Möbius syndrome with misoprostol use, less than one in 1000 births). The use of cocaine (which also has vascular effects) has been implicated in Möbius syndrome.

Some researchers have suggested that the underlying problem of this disorder could be congenital hypoplasia or agenesis of the cranial nerve nuclei. Certain symptoms associated with Möbius syndrome may be caused by incomplete development of facial nerves, other cranial nerves, and other parts of the central nervous system.

The prognosis of this developmental disorder is highly based on the underlying disorder. Cerebellar hypoplasia may be progressive or static in nature. Some cerebellar hypoplasia resulting from congenital brain abnormalities/malformations are not progressive. Progressive cerebellar hypoplasia is known for having poor prognosis, but in cases where this disorder is static, prognosis is better.

Larsen syndrome (LS) is a congenital disorder discovered in 1950 by Larsen and associates when they observed dislocation of the large joints and face anomalies in six of their patients. Patients with Larsen syndrome normally present with a variety of symptoms, including congenital anterior dislocation of the knees, dislocation of the hips and elbows, flattened facial appearance, prominent foreheads, and depressed nasal bridges. Larsen syndrome can also cause a variety of cardiovascular and orthopedic abnormalities. This rare disorder is caused by a genetic defect in the gene encoding filamin B, a cytoplasmic protein that is important in regulating the structure and activity of the cytoskeleton. The gene that influences the emergence of Larsen syndrome is found in chromosome region, 3p21.1-14.1, a region containing human type VII collagen gene. Larsen syndrome has recently been described as a mesenchyme disorder that affects the connective tissue of an individual. Autosomal dominant and recessive forms of the disorder have been reported, although most cases are autosomal dominant. Reports have found that in Western societies, Larsen syndrome can be found in one in every 100,000 births, but this is most likely an underestimate because the disorder is frequently unrecognized or misdiagnosed.

Filamins are cytoplasmic proteins that regulate the structure and activity of the cytoskeleton. These proteins serve as scaffolds on which intracellular signaling and protein trafficking are organized. Filamin B has been found to be expressed in human growth plate chondrocytes, which are especially important in vertebrae segmentation and skeleton morphogenesis. Genetic analysis of patients with Larsen syndrome has found the syndrome is caused by missense mutations in the gene that codes for filamin B. These mutations cause an accelerated rate of apoptosis in the epiphyseal growth plates of individuals with the mutation. The defects can cause short stature and other symptoms associated with Larsen syndrome.

After the last primary tooth is lost, usually around the age of twelve, final orthodontic treatment can be initiated. A patient that has not been able to close or swallow well probably will have an open bite, deficient lower-jaw growth, a narrow archform with crowded teeth, and upper anterior flaring of teeth. Orthognathic (jaw) surgery may be indicated. This should be completed in most situations before the smile surgery where the gracilis muscle is grafted to the face.

Genetic links to 13q12.2 and 1p22 have been suggested.

Keutel syndrome (KS) is a rare autosomal recessive genetic disorder characterized by abnormal diffuse cartilage calcification, hypoplasia of the mid-face, peripheral pulmonary stenosis, hearing loss, short distal phalanges (tips) of the fingers and mild mental retardation. Individuals with KS often present with peripheral pulmonary stenosis, brachytelephalangism, sloping forehead, midface hypoplasia, and receding chin. It is associated with abnormalities in the gene coding for matrix gla protein (MGP). Being an autosomal recessive disorder, it may be inherited from two unaffected, abnormal MGP-carrying parents. Thus, people who inherit two affected MGP genes will likely inherit KS.

It was first identified in 1972 as a novel rare genetic disorder sharing similar symptoms with chondrodysplasia punctata. Multiple forms of chondrodysplasia punctata share symptoms consistent with KS including abnormal cartilage calcification, forceful respiration, brachytelephalangism, hypotonia, psychomotor delay, and conductive deafness, yet peripheral pulmonary stenosis remains unique to KS.

No chromosomal abnormalities are reported in affected individuals, suggesting that familial consanguinity relates to the autosomal recessive mode of inheritance. Also, despite largely abnormal calcification of regions including the larynx, tracheobronchial tree, nose, pinna (anatomy), and epiglottis, patients exhibit normal serum calcium and phosphate levels.

A genetic disorder called “Brickers-Adams-Edwards syndrome” or “X-linked hydrocephalus” has been discovered that leads to aqueductal stenosis. This disease is transmitted from mother to son. This disorder is caused by a point mutation in the gene for neural cell adhesion. Most males born with this have severe hydrocephalus, adducted thumbs, spastic motions, and intellectual problems. Females with this defect may have adducted thumbs or subnormal intelligence.

Bacterial meningitis can also result in gliotic blockage of the aqueduct. In utero infection or infection during infancy could both result in glial cell build up to make an obstruction.

Ectrodactyly–ectodermal dysplasia–cleft syndrome, or EEC, and also referred to as EEC syndrome (also known as "Split hand–split foot–ectodermal dysplasia–cleft syndrome") is a rare form of ectodermal dysplasia, an autosomal dominant disorder inherited as an genetic trait. EEC is characterized by the triad of ectrodactyly, ectodermal dysplasia, and facial clefts. Other features noted in association with EEC include vesicoureteral reflux, recurrent urinary tract infections, obstruction of the nasolacrimal duct, decreased pigmentation of the hair and skin, missing or abnormal teeth, enamel hypoplasia, absent punctae in the lower eyelids, photophobia, occasional cognitive impairment and kidney anomalies, and conductive hearing loss.

3C syndrome is very rare, occurring in less than 1 birth per million. Because of consanguinity due to a founder effect, it is much more common in a remote First Nations village in Manitoba, where 1 in 9 people carries the recessive gene.

Individuals affected by certain ED syndromes cannot perspire. Their sweat glands may function abnormally or may not have developed at all because of inactive proteins in the sweat glands. Without normal sweat production, the body cannot regulate temperature properly. Therefore, overheating is a common problem, especially during hot weather. Access to cool environments is important.

Myhre syndrome is a rare genetic disorder inherited in an autosomal dominant fashion. It is caused by mutation in SMAD4 gene.

Several studies have examined salivary flow rate in individuals and found parotid and submandibular salivary flow ranging from 5 to 15 times lower than average. This is consistent with the salivary glands being of ectodermal origin, although some findings have suggested that there is also mesodermal input.

This condition is a consequence of mutations in the PEX7 gene, GNPAT gene (which is located on chromosome 1) and AGPS gene, the condition is acquired in a autosomal recessive manner.

3C syndrome, also known as CCC dysplasia, Craniocerebellocardiac dysplasia or Ritscher–Schinzel syndrome, is a rare condition, whose symptoms include heart defects, cerebellar hypoplasia, and cranial dysmorphism. It was first described in the medical literature in 1987 by Ritscher and Schinzel, for whom the disorder is sometimes named.

Modeling EEC syndrome in vitro has been achieved by reprogramming EEC fibroblasts carrying mutations R304W and R204W into induced pluripotent stem cell (iPSC) lines. EEC-iPSC recapitulated defective epidermal and corneal fates. This model further identified PRIMA-1MET, a small compound that was identified as a compound targeting and reactivating p53 mutants based on a cell-based screening for rescuing the apoptotic activity of p53, as efficient to rescue R304W mutation defect. Of interest, similar effect had been observed on keratinocytes derived from the same patients. PRIMA-1MET could become an effective therapeutic tool for EEC patients.

Further genetic research is necessary to identify and rule out other possible loci contributing to EEC syndrome, though it seems certain that disruption of the p63 gene is involved to some extent. In addition, genetic research with an emphasis on genetic syndrome differentiation should prove to be very useful in distinguishing between syndromes that present with very similar clinical findings. There is much debate in current literature regarding clinical markers for syndromic diagnoses. Genetic findings could have great implications in clinical diagnosis and treatment of not only EEC, but also many other related syndromes.

Oculofaciocardiodental syndrome is a rare X linked genetic disorder.

Individuals with Nager syndrome typically have the malformations of the auricle, external auditory canal, and middle ear, including the ossicles. These malformations were found in 80% of individuals with Nager syndrome. Inner ear malformations, however, are not typically seen in this population. Middle ear disease is common among individuals with Nager syndrome. Chronic otitis media and Eustachian tube deformity can result in conductive hearing loss. For this reason, early detection and treatment for middle ear disease is crucial in this population. Sensorineural hearing loss is not a typical characteristic of Nager syndrome; however, a subset of individuals present with a mixed hearing loss, due to a progressive sensorineural component combined with the typical conductive hearing loss (Herrman "et al.", 2005).

There is no standard course of treatment for cerebellar hypoplasia. Treatment depends upon the underlying disorder and the severity of symptoms. Generally, treatment is symptomatic and supportive. Balance rehabilitation techniques may benefit those experiencing difficulty with balance. Treatment is based on the underlying disorder and the symptom severity. Therapies include physical, occuptational, speech/language, visual, psych/ behavioral meds, special education.

Nasodigitoacoustic syndrome, also called Keipert syndrome, is a rare congenital syndrome first described by J.A. Keipert and colleagues in 1973. The syndrome is characterized by a mishaped nose, broad thumbs and halluces (the big toes), brachydactyly, sensorineural hearing loss, facial features such as hypertelorism (unusually wide-set eyes), and developmental delay. It is believed to be inherited in an X-linked recessive manner, which means a genetic mutation causing the disorder is located on the X chromosome, and while two copies of the mutated gene must be inherited for a female to be born with the disorder, just one copy is sufficient to cause a male to be born with the disorder. Nasodigitoacoustic syndrome is likely caused by a mutated gene located on the X chromosome between positions Xq22.2–q28. The incidence of the syndrome has not been determined, but it is considered to affect less than 200,000 people in the United States, and no greater than 1 per 2,000 in Europe. It is similar to Keutel, Muenke, Rubinstein and Teunissen-Cremers syndrome.

Hearing loss with craniofacial syndromes is a common occurrence. Many of these multianomaly disorders involve structural malformations of the outer or middle ear, making a significant hearing loss highly likely.