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.

Some people may have some mental slowness, but children with this condition often have good social skills. Some males may have problems with fertility.

Males are twice as likely as females to have this characteristic, and it tends to run in families. In its non-symptomatic form, it is more common among Asians and Native Americans than among other populations, and in some families there is a tendency to inherit the condition unilaterally, that is, on one hand only.

The presence of a single transverse palmar crease can be, but is not always, a symptom associated with abnormal medical conditions, such as fetal alcohol syndrome, or with genetic chromosomal abnormalities, including Down Syndrome (chromosome 21), cri du chat syndrome (chromosome 5), Klinefelter syndrome, Wolf-Hirschhorn Syndrome, Noonan syndrome (chromosome 12), Patau syndrome (chromosome 13), IDIC 15/Dup15q (chromosome 15), Edward's syndrome (chromosome 18), and Aarskog-Scott syndrome (X-linked recessive), or autosomal recessive disorder, such as Leaukocyte adhesion deficiency-2 (LAD2). A unilateral single palmar crease was also reported in a case of chromosome 9 mutation causing Nevoid basal cell carcinoma syndrome and Robinow syndrome. It is also sometimes found on the hand of the affected side of patients with Poland Syndrome, and craniosynostosis.

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.

It remains unconfirmed whether composer Sergei Rachmaninoff's abnormally large reach on a piano was a result of arachnodactyly due to Marfan syndrome, as the pianist exhibited no other signs of the disease.

More than 80% of children with Patau syndrome die within the first year of life. Children with the mosaic variation are usually affected to a lesser extent. In a retrospective Canadian study of 174 children with trisomy 13, median survival time was 12.5 days. One and ten year survival was 19.8% and 12.9% respectively.

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

Mutations in the FGD1 gene are the only known genetic cause of Aarskog-Scott syndrome. The FGD1 gene provides instructions for making a protein that turns on (activates) another protein called Cdc42, which transmits signals that are important for various aspects of development before and after birth.

Mutations in the FGD1 gene lead to the production of an abnormally functioning protein. These mutations disrupt Cdc42 signaling, leading to the wide variety of abnormalities that occur in people with Aarskog-Scott syndrome.

Only about 20 percent of people with this disorder have identifiable mutations in the FGD1 gene. The cause of Aarskog-Scott syndrome in other affected individuals is unknown.

This feature can occur on its own, with no underlying health problems. However, it can also be associated with certain medical conditions. Examples include Marfan syndrome, Ehlers-Danlos syndrome, Loeys–Dietz syndrome, congenital contractural arachnodactyly, and homocystinuria.

Arachnodactyly has been linked to mutations in both fibrillin-1 and fibrillin-2 genes.

Omphalocele has been described in two patients with Apert syndrome by Herman T.E. et al. (USA, 2010) and by Ercoli G. et al. (Argentina, 2014). An omphalocele is a birth defect in which an intestine or other abdominal organs are outside of the body of an infant because of a hole in the bellybutton area. However, the association between omphalocele and Apert syndrome is not confirmed yet, so additional studies are necessary.

Minor degrees of curvature are common. Reports of incidence vary between 1% and 19.5%.

Smith–Fineman–Myers syndrome (SFMS1), congenital disorder that causes birth defects. This syndrome was named after 3 men, Richard D. Smith, Robert M. Fineman and Gart G. Myers who discovered it around 1980.

Clinodactyly is an autosomal dominant trait that has variable expressiveness and incomplete penetrance.

Clinodactyly can be passed through inheritance and presents as either an isolated anomaly or a component manifestation of a genetic syndrome. Many syndromes are associated with clinodactyly, including Down Syndrome, Turner syndrome, Aarskog syndrome, Carpenter syndrome, Seckel syndrome, Cornelia de Lange syndrome, orofaciodigital syndrome 1, 13q deletion syndrome, XXYY syndrome and Silver–Russell syndrome.

When identified prenatally, for example during obstetric ultrasonography, it may be an indication for intrauterine sampling for fetal chromosome analysis as it is statistically correlated with increased risk of chromosome aberration in the fetus.

SFMS is an X-linked disease by chromosome Xq13. X-linked diseases map to the human X chromosome because this syndrome is an X chromosome linked females who have two chromosomes are not affected but because males only have one X chromosome, they are more likely to be affected and show the full clinical symptoms. This disease only requires one copy of the abnormal X-linked gene to display the syndrome. Since females have two X chromosomes, the effect of one X chromosome is recessive and the second chromosome masks the affected chromosome.

Affected fathers can never pass this X-linked disease to their sons but affected fathers can pass the X-linked gene to their daughters who has a 50% chance to pass this disease-causing gene to each of her children. Since females who inherit this gene do not show symptoms, they are called carriers. Each of the female's carrier's son has a 50% chance to display the symptoms but none of the female carrier's daughters would display any symptoms.

Some patients with SFMS have been founded to have a mutation of the gene in the ATRX on the X chromosome, also known as the Xq13 location. ATRX is a gene disease that is associated with other forms of X-linked mental retardation like Alpha-thalassemia/mental retardation syndrome, Carpenter syndrome, Juberg-Marsidi syndrome, and soastic paraplegia. It is possible that patients with SFMS have Alpha-thalassemia/mental retardation syndrome without the affected hemoglobin H that leads to Alphathalassemia/ mental retardation syndrome in the traditionally recognized disease.

Patau syndrome is the result of trisomy 13, meaning each cell in the body has three copies of chromosome 13 instead of the usual two. A small percentage of cases occur when only some of the body's cells have an extra copy; such cases are called mosaic Patau.

Patau syndrome can also occur when part of chromosome 13 becomes attached to another chromosome (translocated) before or at conception in a Robertsonian translocation. Affected people have two copies of chromosome 13, plus extra material from chromosome 13 attached to another chromosome. With a translocation, the person has a partial trisomy for chromosome 13 and often the physical signs of the syndrome differ from the typical Patau syndrome.

Most cases of Patau syndrome are not inherited, but occur as random events during the formation of reproductive cells (eggs and sperm). An error in cell division called non-disjunction can result in reproductive cells with an abnormal number of chromosomes. For example, an egg or sperm cell may gain an extra copy of the chromosome. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have an extra chromosome 13 in each of the body's cells. Mosaic Patau syndrome is also not inherited. It occurs as a random error during cell division early in fetal development.

Patau syndrome due to a translocation can be inherited. An unaffected person can carry a rearrangement of genetic material between chromosome 13 and another chromosome. This rearrangement is called a balanced translocation because there is no extra material from chromosome 13. Although they do not have signs of Patau syndrome, people who carry this type of balanced translocation are at an increased risk of having children with the condition.

In humans, a single transverse palmar crease is a single crease that extends across the palm of the hand, formed by the fusion of the two palmar creases (known in palmistry as the "heart line" and the "head line") and is found in people with Down Syndrome. It is also found in 1.5% of the general population in at least one hand.

Because it resembles the usual condition of non-human simians, it is also known as a simian crease or simian line, although these terms have widely fallen out of favor due to their pejorative connotation.

Acrocephalosyndactylia (or acrocephalosyndactyly) is the common presentation of craniosynostosis and syndactyly.

It has several different types:

- type 1 - Apert syndrome

- type 2 - Crouzon syndrome

- type 3 - Saethre-Chotzen syndrome

- type 5 - Pfeiffer syndrome

A related term, "acrocephalopolysyndactyly" (ACPS), refers to the inclusion of polydactyly to the presentation. It also has multiple types:

- type 1 - Noack syndrome; now classified with Pfeiffer syndrome

- type 2 - Carpenter syndrome

- type 3 - Sakati-Nyhan-Tisdale syndrome

- type 4 - Goodman syndrome; now classified with Carpenter syndrome

- type 5 - Pfeiffer syndrome

It has been suggested that the distinction between "acrocephalosyndactyly" versus "acrocephalopolysyndactyly" should be abandoned.

Acrocephalosyndactyly may be an autosomal dominant disorder. Males and females are affected equally; however research is yet to determine an exact cause. Nonetheless, almost all cases are sporadic, signifying fresh mutations or environmental insult to the genome. The offspring of a parent with Apert syndrome has a 50% chance of inheriting the condition. In 1995, A.O.M. Wilkie published a paper showing evidence that acrocephalosyndactyly is caused by a defect on the fibroblast growth factor receptor 2 gene, on chromosome 10.

Apert syndrome is an autosomal dominant disorder; approximately two-thirds of the cases are due to a C to G mutation at the position 755 in the FGFR2 gene, which causes a Ser to Trp change in the protein. This is a male-specific mutation hotspot: in a study of 57 cases, the mutation always occurred on the paternally derived allele. On the basis of the observed birth prevalence of the disease (1 in 70,000), the apparent rate of C to G mutations at this site is about .00005, which is 200- to 800-fold higher than the usual rate for mutations at CG dinucleotides. Moreover, the incidence rises sharply with the age of the father. Goriely et al. (2003) analyzed the allelic distribution of mutations in sperm samples from men of different ages and concluded that the simplest explanation for the data is that the C to G mutation gives the cell an advantage in the male germline.

It is still not very clear why people with Apert Syndrome have both craniosynostosis and syndactyly. There has been one study that suggests it has something to do with the expression of three isoforms of FGFR2, the gene with the point mutations that causes the syndrome in 98% of the patients.

KGFR, keratinocyte growth factor receptor, is an isoform active in the metaphysis and interphalangeal joints. FGFR1 is an isoform active in the diaphysis. FGFR2-Bek is active in the metaphysis, as well as the diaphysis, but also in the interdigital mesenchyme. The point mutation increases the ligand-dependent activation of FGFR2, and thus of its isoforms. This means that FGFR2 loses its specificity, causing binding of FGFs that normally do not bind to the receptor. Since FGF suppresses apoptosis, the interdigital mesenchyme is maintained. FGF also increases replication and differentiation of osteoblasts, thus early fusion of several sutures of the skull. This may explain why both symptoms are always found in Apert Syndrome.

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.

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.

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.

Very few risk factors for choanal atresia have been identified. While causes are unknown, both genetic and environmental triggers are suspected. One study suggests that chemicals that act as endocrine disrupters may put an unborn infant at risk. A 2012 epidemiological study looked at atrazine, a commonly used herbicide in the U.S., and found that women who lived in counties in Texas with the highest levels of this chemical being used to treat agricultural crops were 80 times more likely to give birth to infants with choanal atresia or stenosis compared to women who lived in the counties with the lowest levels. Another epidemiological report in 2010 found even higher associations between increased incidents of choanal atresia and exposure to second-hand-smoke, coffee consumption, high maternal zinc and B-12 intake and exposure to anti-infective urinary tract medications.

In the above brachydactyly syndromes, short digits are the most prominent of the anomalies, but in many other syndromes (Down syndrome, Rubinstein-Taybi syndrome, etc.), brachydactyly is a minor feature compared to the other anomalies or problems comprising the syndrome.