Preaxial polydactyly of the foot

Abstract

Background and purpose - Preaxial polydactyly of the foot is a rare malformation and clinicians are often unfamiliar with the associated malformations and syndromes. In order to give guidelines for diagnostics and referral to a clinical geneticist, we provide an overview of the presentation using a literature review and our own patient population. Patients and methods - The literature review was based on the Human Phenotype Ontology (HPO) project. From the HPO dataset, all phenotypes describing preaxial polydactyly were obtained and related diseases were identified and selected. An overview was generated in a heatmap, in which the phenotypic contribution of 12 anatomical groups to each disease is displayed. Clinical cases were obtained from our hospital database and were reviewed in terms of phenotype, genotype, heredity, and diagnosed syndromes. Results - From the HPO dataset, 21 diseases were related to preaxial polydactyly of the foot. The anatomical groups with the highest phenotypic contribution were lower limb, upper limb, and craniofacial. From our clinical database, we included 76 patients with 9 different diseases, of which 27 had a GLI3 mutation. Lower limb malformations (n = 55), upper limb malformations (n = 59), and craniofacial malformations (n = 32) were most frequently observed. Malformations in other anatomical groups were observed in 27 patients. Interpretation - Preaxial polydactyly of the foot often presents with other upper and lower limb malformations. In patients with isolated preaxial polydactyly of the foot, referral to a clinical geneticist is not mandatory. In patients with additional malformations, consultation with a clinical geneticist is recommended. When additional limb malformations are present, analysis of GLI3 is most feasible.

Figure 1.

Heatmap showing the contribution of each anatomical group per disease related to preaxial polydactyly of the foot. The contribution of each anatomical group per disease is expressed by a red color gradient. No contribution = white; maximal contribution = red. The group of preaxial polydactyly consists of preaxial polydactyly type 1, preaxial polydactyly type 2, and preaxial polydactyly type 4. These subtypes are considered as independent disease entities, but are combined in one column because contribution of each anatomical group is similar in every type.

Figure 2.

Example of preaxial polydactyly of the foot and some related phenotypes. A and B. Preaxial polydactyly of the foot. C. Typical hand malformation in Greig syndrome: Preaxial and postaxial polydactyly of the hand. D. Typical malformation in orofacial-digital syndrome: Tongue malformation indicated by the arrow. E. Typical craniofacial malformations in craniofrontonasal dysplasia syndrome: craniosynostosis, hypertelorism, and facial asymmetry.