Clinical and genetic studies on 12 preaxial polydactyly families and refinement of the localisation of the gene responsible to a 1.9 cM region on chromosome 7q36.

Polydactyly is the most frequently observed congenital hand malformation with a prevalence between 5 and 19 per 10000 live births. It can occur as an isolated disorder, in association with other hand/foot malformations, or as a part of a syndrome, and is usually inherited as an autosomal dominant trait. According to its anatomical location, polydactyly can be generally subdivided into pre- and postaxial forms. Recently, a gene responsible for preaxial polydactyly types II and III, as well as complex polysyndactyly, has been localised to chromosome 7q36. In order to facilitate the search for the underlying genetic defect, we ascertained 12 additional families of different ethnic origin affected with preaxial polydactyly. Eleven of the kindreds investigated could be linked to chromosome 7q36, enabling us to refine the critical region for the preaxial polydactyly gene to a region of 1.9 cM. Our findings also indicate that radial and tibial dysplasia/aplasia can be associated with preaxial polydactyly on chromosome 7q36. Combining our results with other studies suggests that all non-syndromic preaxial polydactylies associated with triphalangism of the thumb are caused by a single genetic locus, but that there is genetic heterogeneity for preaxial polydactyly associated with duplications of biphalangeal thumbs. Comparison of the phenotypic and genetic findings of different forms of preaxial polydactyly is an important step in analysing and understanding the aetiology and pathogenesis of these limb malformations.

Psychomotor development in children with triphalangeal thumbs. A preliminary study.

In order to explore the influence of an isolated congenital hand malformation on psychomotor development, we performed an exploratory, observational study on 18 children with triphalangeal thumbs. The investigative procedure consisted of a hand function examination, a semi-structured interview with the mother about the development of the child, the so-called "Hand test", and the "Child Behaviour Check List". Our observations suggest specific developmental difficulties in fine motor skills and language development, but the children showed no signs of behavioural psychopathology.

Genetics of limb development and congenital hand malformations.

The vertebrate limb bud develops along three different axes: proximodistal, anteroposterior, and dorsoventral. Several genetic factors responsible for control of each of the three limb axes have been identified. The genes involved interact in complex feedback loops to achieve proper arrangement and differentiation of tissues. Most of the available information on limb development and patterning has come from studies carried out in the lower vertebrates. In recent years, an increasing number of studies have been unraveling the genetic basis of human hand malformation phenotypes. At present, genes responsible for preaxial polydactyly, split hand/split foot malformation, and brachydactyly type C have been localized, and the gene responsible for synpolydactyly has been identified. In this paper, we present an overview of the genetic factors involved in limb development, followed by summarized discoveries in the genetics of human congenital hand malformations.

The role of metacarpophalangeal pattern (MCPP) profile analysis in the treatment of triphalangeal thumbs. Description of a method and a case report.

The metacarpophalangeal pattern (MCPP) profile analysis is a method of comparing the length of each of the 19 tubular bones of the hand on the X-ray with the standard length in the normal population according to age and sex. An MCPP plot is a graphic illustration of the MCPP analysis. It is not the exact height of the curve on the MCPP plot which is most important, but the profile which occurs because of the individual lengthening or shortening of the bones. This pattern profile appears to be specific for several congenital malformation syndromes. We have recently used MCPP analysis in planning surgery for triphalangeal thumbs. The percentage of excessive or reduced length of each individual bone of the hand can be read from the MCPP plot and is helpful in calculating a more accurate length for the newly created thumb. MCPP analysis can be used as a diagnostic tool in a number of congenital hand malformations, but may also be helpful in planning surgical treatment of congenital hand malformations when abnormal bone length is involved.