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.

The cause of frontorhiny is a mutation in the ALX3 gene. ALX3 is essential for normal facial development. Different mutations can occur in the ALX3 gene, but they all lead to the same effect: severe or complete loss of protein functionality. The ALX3 mutation never occurs in a person without frontorhiny.

Environmental factors refer for example to maternal smoking and the maternal exposure to amine-containing drugs. Several research groups have found evidence that these environmental factors are responsible for an increase in the risk of craniosynostosis, likely through effects on fibroblast growth factor receptor genes.

On the other hand, a recent evaluation of valproic acid (an anti-epilepticum), which has been implicated as a causative agent, has shown no association with craniosynostosis.

Certain medication (like amine-containing drugs) can increase the risk of craniosynostosis when taken during pregnancy, these are so-called teratogenic factors.

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.

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.

The exact cause of the condition is unknown. In some cases, close family members may share this condition. In other cases, no other related persons have this condition. The scientific name for the condition is syndactyly, although this term covers both webbed fingers and webbed toes. Syndactyly occurs when apoptosis or programmed cell death during gestation is absent or incomplete. Webbed toes occur most commonly in the following circumstances:

- Syndactyly or Familial Syndactyly

- Down syndrome

It is also associated with a number of rare conditions, notably:

- Aarskog–Scott syndrome

- Acrocallosal syndrome

- Apert's syndrome

- Bardet-Biedl syndrome

- Carpenter syndrome

- Cornelia de Lange syndrome

- Edwards syndrome

- Jackson–Weiss syndrome

- Fetal hydantoin syndrome

- Miller syndrome

- Pfeiffer syndrome

- Smith-Lemli-Opitz syndrome

- Timothy syndrome

- Ectodermal Dysplasia

- Klippel-Feil Syndrome

SCS is the most common craniosynostosis syndrome and affects 1 in every 25,000 to 50,000 individuals. It occurs in all racial and ethnic groups, and affects males and females equally. If a parent carries a copy of the SCS gene mutation, then there is a 50% chance their child will also carry a copy of the gene mutation, in which case, the child may or may not show signs of SCS. There is also a 50% chance their child will have two working copies of the gene, and would therefore, not have SCS. If both parents carry a single copy of the SCS gene mutation, then there is a 25% chance their child will have two gene mutation copies (so child would develop severe SCS), a 25% chance their child would have two normal copies of the gene (so would be completely normal), and a 50% chance their child would carry one gene mutation copy and 1 normal copy (so child may or may not display SCS). In rare situations, two normal parents can have a child with SCS due to a "de novo" mutation. The exact cause of the "de novo" mutation is unknown, but it doesn't seem to be related to anything that the parents did or didn't do during the pregnancy. SCS due to a "de novo" mutation is so rare that the proportion of past cases is unknown.

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.

Biomechanical factors include fetal head constraint during pregnancy. It has been found by Jacob et al. that constraint inside the womb is associated with decreased expression of Indian Hedgehog protein and noggin. These last two are both important factors influencing bone development.

Prenatal diagnosis of Saethre-Chotzen Syndrome in high risk pregnancies is doable, but very uncommon and rarely performed. Furthermore, this is only possible if the mutation causing the disease has already been identified within the family genome. There are a few different techniques in which prenatal testing can be carried out. Prenatal testing is usually performed around 15–18 weeks, using amniocentesis to extract DNA from the fetus's cells. Prenatal testing can also be performed during weeks 10-12 using chorionic villus sampling (CVS) to extract DNA from the fetus. Recently, there has been an increased interest in utilizing ultrasound equipment in order to detect fetal skull abnormalities due to immature fusion of the cranial sutures.

Symbrachydactyly is a congenital abnormality, characterized by limb anomalies consisting of brachydactyly, cutaneous syndactyly and global hypoplasia of the hand or foot. In many cases, bones will be missing from the fingers and some fingers or toes may be missing altogether. The ends of the hand may have "nubbins"—small stumps where the finger would have developed, which may have tiny residual nails.

Symbrachydactyly has been reported to appear without other combined limb anomalies and usually in one arm in 1 in 30,000 births to 1 in 40,000 births.

The cause of symbrachydactyly is unknown. One possible cause might be an interruption of the blood supply to the developing arm at four to six weeks of pregnancy. There is no link to anything the mother did or did not do during pregnancy. There is also no increased risk of having another child with the same condition or that the child will pass the condition on to his or her children.

In most cases, children born with symbrachydactyly are able to adapt to their physical limitations and experience a fully functional life with no treatment. Most children with this condition can use their hands well enough to do all the usual things children do. Possible treatment includes surgery or a routine of regularly stretching the fingers.

According to the National Human Genome Research Institute, Poland syndrome affects males three times as often as females and affects the right side of the body twice as often as the left. The incidence is estimated to range from one in 7,000 to one in 100,000 live births.

Webbed toes in humans are a purely cosmetic condition. This condition does not impair the ability to perform any activity, including walking, running, or swimming. Depending on the severity and structure of the webbing, there can be some minor consequences.

People with more severe webbed toes may have a slight disadvantage for activities that benefit from prehensile toes, due to the toes being unable to split or move laterally. Although not scientifically proven, some believe that this condition can possibly allow for a slight advantage, specifically, in athletics. Considering your big toe is a main source for balance, having your second and third toe webbed could virtually be seen as having two big toes. Thus, allowing for better balance in athletics such as running or dance.

Psychological stress may arise from the fear of negative reactions to this condition from people who do not have webbed toes, particularly in severe cases where the nails are stuck visibly close together. Many people with webbed toes can physically feel the toes touching under the fused skin, which can cause psychological discomfort. This is due to the nerves of each toe fully developing and independent muscles working. In other cases where the toes are partially webbed, the webbing holds the separate tips of the toes against one another and prevents the muscles from spreading the toes apart, causing the toes and sometimes nails to press together.

However a disadvantage would be a difficulty in wearing flip-flops or other such footwear in warm countries. People with webbed toes may be unable to wear Toe socks or Vibram FiveFingers shoes. Difficulty navigating rough terrain barefoot, such as rocks at a beach is also common. In some cases the toes grow at different lengths causing the toes to buckle or bend and many people with severe webbed toes experience cramping in these toes due to the muscles and ligaments being strained.

Children with Pfeiffer syndrome types 2 and 3 "have a higher risk for neurodevelopmental disorders and a reduced life expectancy" than children with Pfeiffer syndrome type 1, but if treated, favorable outcomes are possible. In severe cases, respiratory and neurological complications often lead to early death.

The cause of Poland syndrome is unknown. However, an interruption of the embryonic blood supply to the arteries that lie under the collarbone (subclavian arteries) at about the 46th day of embryonic development is the prevailing theory.

The subclavian arteries normally supply blood to embryonic tissues that give rise to the chest wall and hand. Variations in the site and extent of the disruption may explain the range of signs and symptoms that occur in Poland syndrome. Abnormality of an embryonic structure called the apical ectodermal ridge, which helps direct early limb development, may also be involved in this disorder.

Muenke syndrome is caused by a specific gene mutation in the FGFR3 gene. The mutation arises randomly; there is no full understanding for what causes this mutation. This mutation causes the FGFR3 protein to be overly active; it interferes with normal bone growth, and allows skull bones to fuse prematurely. There is no connection between anything mother did (or did not do) to activate the syndrome. If neither of the parents have Muenke syndrome, chances of having another child with the syndrome are minimal.

This condition is inherited in an autosomal dominant pattern. This means if a parent has Muenke syndrome, every newborn has a 50% chance of inheriting the syndrome.

The cause of fibular hemimelia is unclear. Purportedly, there have been some incidents of genetic distribution in a family; however, this does not account for all cases. Maternal viral infections, embryonic trauma, teratogenic environmental exposures or vascular dysgenesis (failure of the embryo to form a satisfactory blood supply) between four and seven weeks gestation are considered possible causes.

In an experimental mouse model, change in the expression of a homeobox gene led to similar, but bilateral, fibular defects.

Muenke syndrome, also known as FGFR3-related craniosynostosis, is a human specific condition characterized by the premature closure of certain bones of the skull during development, which affects the shape of the head and face. First described by Maximilian Muenke, the syndrome occurs in about 1 in 30,000 newborns. This condition accounts for an estimated 8 percent of all cases of craniosynostosis.

Five types of syndactyly have been identified in humans. The corresponding loci associated with these types and their common phenotypical expression are as follows:

- "type I": 2q34-q36; webbing occurs between middle and ring fingers and/or second and third toes.

- "type II": 2q31; also involves long and ring fingers, but has a sixth finger merged in between.

- "type III": 6q21-q23; small finger is merged into the ring finger.

- "type IV": 7q36; involves all fingers and/or toes.

- "type V": 2q31-q32; similar to type I, but the metacarpals and metatarsals may also be fused.

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.

Brachymetatarsia is found to occur more frequently in women than men.

Syndactyly (from Greek συν- meaning "together" and δακτυλος meaning "finger") is a condition wherein two or more digits are fused together. It occurs normally in some mammals, such as the siamang and diprotodontia, but is an unusual condition in humans.

Most children with symbrachydactyly have excellent function in daily activities. Due to the length of their arm, they do not qualify for most artificial limbs. However, some adaptive prosthetics and equipment for sports and leisure activities may be helpful when the child is older. Children who demonstrate some functional movement in their remaining fingers and within the palm are evaluated for possible surgery such as toe transfers.

The key problem is the early fusion of the skull, which can be corrected by a series of surgical procedures, often within the first three months after birth. Later surgeries are necessary to correct respiratory and facial deformities.

Dysmelia can be caused by

- inheritance of abnormal genes, e.g. polydactyly, ectrodactyly or brachydactyly, symptoms of deformed limbs then often occur in combination with other symptoms (syndromes)

- external causes during pregnancy (thus not inherited), e.g. via amniotic band syndrome

- teratogenic drugs (e.g. thalidomide, which causes phocomelia) or environmental chemicals

- ionizing radiation (nuclear weapons, radioiodine, radiation therapy)

- infections

- metabolic imbalance