Polydactylism Polydactyly Is a Relatively

Polydactylism

Polydactyly is a relatively common condition in which extra digits on the foot or hand develop during growth of the fetus. This essay presents a discussion of the organs and cells which are affected, along with a discussion of the genetic basis of the condition. Finally, there is a brief discussion of the treatments which are available for the condition.

Specific Organs and Systems Affected

Polydactylism is a condition which results in duplicated digits on the hand or foot (Turra et al., 2007). These range from being small pieces of soft tissue to being fully formed in appearance (NationMaster, 2005). It is noted that in around 80% to 90% of cases involve the peripheral digits, although it is possible that all digits may be affected. Due to the development patterns of polydactylism the classification of the disorder is based on digits affected, as the condition starts peripherally and then spreads to the centre (Borisch et al., 1995). Postaxial polydactyly is that in which it is the fifth digit of the hands or feet which is duplicated. Furthermore, there are two different phenotypes of this form of polydactyly which have been described: type a and type B. In type a, the extra digit is well formed, and in some cases may appear almost whole. In contrast, type B is characterized instead by a rudimentary extra digit (Zhao et al., 2002). A study by Watson and Hennrikus (1997) suggested that in type B polydactyly it may be relatively common to find bilateral polydactyly of the hands. Their study found that 76% of those having duplicated fingers had them on both hands to some extent.

It is possible that polydactylism may occur in isolation or that it may occur as only one element of a more complex condition. For example polydactylism may occur as one element of Bardet-Biedl syndrome. This is an autosomal recessive condition which is also characterized by obesity, mental retardation, short stature and a number of other physical manifestations (Palmer, 2006). This is one of numerous different conditions which may include some form of polydactylism as a characteristic symptom.

Specific Cells Affected

Relatively early work into the cellular developmental process involved in development of polydactylism showed that it is caused by a defect in the cell death process in the embryo. In particular, Scott et al. (1977) found that when the lifespan of ectodermal cells was prolonged this led to an increase in the inductive activity of the underlying mesoderm. It was this increased activity which then created the excess tissue which resulted in the extra digits. This therefore was suggestive of an underlying fault in the cell death process which resulted in prevention of death of these ectodermal cells.

Work by Klein and colleagues (1981) with rat models examined the effect of giving pregnant rats high doses of aspirin. On observation it was found that this created a unique pattern of preaxial mesodermal cell death in hindlimb buds. This pattern involved a delay of the normal cell death which occurred in preaxial apical ectodermal ridge. In addition, there was also a complete absence of cell death in a specific zone of physiological necrosis within the preaxial mesoderm, the same area which is believed to be critical in preaxial digit formation.

More recent work has shown that the identity and number of digits is determined in the embryo by patterning along the antero-posterior axis of the developing limb (Tickle, 2006). This is controlled by a zone of polarizing activity (ZPA), the cells of which produce a signaling molecule sonic hedgehog (SHH) to control the patterning process. It is therefore the mechanism which regulates Shh gene expression which is implicated in polydactylism, specifically preaxial polydactylism. There is a cis-acting regulatory element which has been identified as driving Shh expression, and it is this which has been suggested to be the primary location of mutations in the condition (Hill, 2007). Maas and Fallon (2005) also found that the ectopic expression of Shh in the anterior region of the developing limb in contrast to only the normal posterior expression was associated with polydactyly. This study also discussed the discovery of an enhancer of the Shh gene expression which is found around 1 Mb upstream from the Shh transcription initiation site. This regulatory element is known as ZRS. Despite this being a long-range effector, it is thought that this may also play a role in polydactyly development. Work by Gurnett and colleagues (2007) found that point mutations in ZRS were present in those with triphalangeal thumb, which is further evidence that genetic defects in this part of the cell may be a causative factor in polydactyly.

Genetics

There is some debate over the precise incidence of polydactylism, although it estimated that the condition has an incidence of around 2 children in every 1000, although this is known to vary by population (NationMaster, 2005). It is possible that polydactylism may be a result of hereditary causes in some cases. Preaxial polydactyl in particular has been shown to have a number of different genetic causes (Hill, 2007). One of the most common is that which maps to the human chromosome 7q36, and this is known to occur in one in around 2000 births. In this instance it is a t (5,7)(q11,q36) translocation which has been shown to be crucial in creating the polydactyl phenotype (Lettice et al., 2002). Work by Maas and Fallon (2005) also supported the concept that the genetic basis for preaxial polydactyly is likely to be due to a single base pair change.

A study by Kuru and colleagues (2006) in Turkey investigated a family in which polydactylism of both hands and feet had been identified some years ago. The study found that over time there was an increase in offspring who were homozygous for the condition. These homozygous offspring still displayed clinical polysyndactylism in which digits were underdeveloped, unshaped and fused. The study also found that from both clinical and surgical perspectives the deformations of offspring were different to those of their parents. Although this homozygous polydactylism is considered a separate strain of polysyndactyly it demonstrates that it is possible that the condition may not be a recessive trait.

Studies have also been conducted into the genetic basis of postaxial polysyndactyly. A screening study of 11,161 newborns in America suggests that postaxial polydactyly, particularly type B polydactyly, may be more common than preaxial polydactyly. This study found an incidence of one in 531 births, and of these cases, 86% had a family history of the condition (Watson & Henrikus, 1997). Zhao and colleagues (2002) found that in some cases of postaxial polysyndactyly in the Chinese population, the condition was caused by mutations in the GLI3 gene, and some cases were also associated with a second locus on chromosome 13.

Another study by Boeing et al. (2001) in Brazil also found that family history was a predictive factor in congenital malformation. In addition to this, the study also suggested that ethnicity may play a role in increasing risk. Researchers found that those with African ancestry were at increased risk of developing polydactylism. This echoes earlier work which also suggested that there was an excess of a mild form of polydactylism in black populations (Kalter, 2003).

Aside from hereditary causes, it is also possible that environmental effects could cause the genetic defects in the fetus. Various studies into animal models have identified a number of environmental elements which may create teratogenic effects such as those seen in polydactylism. One example is the study by Saito and colleagues (2006) which found that strong magnetic fields may lead to the development of polydactylism in exposed fetuses among other deformities. Other examples of environmental effects which have received significant attention in relation to congenital birth defects such as polydactyly are maternal habits such as smoking and alcohol consumption. West and colleagues (1981) conducted a study into the impact of dosing maternal rats with ethanol and found that this resulted in the occurrence of polydactyly in offspring.

Therapies or Treatments