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.

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

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.

There are approximately three hundred known cases of Carpenter Syndrome in the United States. Only 1 in 1 million live births will result in an infant affected by Carpenter Syndrome (RN, 2007).

Carpenter Syndrome is an autosomal recessive disease which means both parents must have the faulty genes in order to pass the disease onto their children. Even if both parents possess the faulty gene there is still only a twenty five percent chance that they will produce a child affected by the syndrome. Their children who do not have the disease will still be carriers and possess the ability to pass the disease onto their offspring if their spouse is also a carrier of the particular gene.

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).

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.

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.

Malformations of the upper extremities can occur In the third to seventh embryonic week. In some cases the TPT is hereditary. In these cases, there is a mutation on chromosome 7q36. If the TPT is hereditary, it is mostly inherited as an autosomal dominant trait, non-opposable and bilateral. The sporadic cases are mostly opposable and unilateral.

Triphalangeal thumb can occur in syndromes but it can also be isolated. The triphalangeal thumb can appear in combination with other malformations or syndromes.

Syndromes include:

- Holt-Oram syndrome

- Aase syndrome

- Blackfan-Diamond syndrome

- Townes-Brocks syndrome

Malformations include:

- Radial polydactyly

- Syndactyly

- Claw-like hand or foot

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.

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.

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

Synpolydactyly is a joint presentation of syndactyly (fusion of digits) and polydactyly (production of supernumerary digits). This is often a result of a mutation in the HOX D13 gene.

Types include:

Three main support groups of this syndrome are the ASGA in Australia, The Association for Children with Genetic Disorders in Poland, and the Association of People of Genetic Disorders in Greece.

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.

Congenital limb deformities are congenital musculoskeletal disorders which primarily affect the upper and lower limbs.

An example is polydactyly.

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 Wassel classification is used to categorise radial polydactyly, based upon the most proximal level of skeletal duplication.

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.

Dysmelia can refer to

- missing (aplasia) limbs: amelia, oligodactyly, congenital amputation e.g. Tibial or Radial aplasia

- malformation of limbs: shortening (micromelia, rhizomelia or mesomelia), ectrodactyly, phocomelia, meromelia, syndactyly, brachydactyly, club foot

- too many limbs: polymelia, polydactyly, polysyndactyly

- others: Tetraamelia, hemimelia, Symbrachydactyly

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.

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.

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 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.