Preaxial polydactyly of the foot

Abstract

Background and purposePreaxial 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 methodsThe 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.ResultsFrom 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.InterpretationPreaxial 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.

Two Cases of Preaxial Polydactyly of the Foot: Important Implications for Plastic Surgeons

“…Nearly half of all patients with preaxial polydactyly of the foot have multiple congenital anomalies, which can range from benign differences like syndactyly or macrocephaly to severe malformations, such as craniosynostosis, corpus callosum agenesis, or renal agenesis. 2 , 3 , 7 Burger and colleagues identified 21 distinct disease entities associated with preaxial polydactyly of the foot and proposed 3 main groups based on phenotype. 7 …”

“… 2 , 3 , 7 Burger and colleagues identified 21 distinct disease entities associated with preaxial polydactyly of the foot and proposed 3 main groups based on phenotype. 7 …”

“…Patients in the first group have isolated preaxial polydactyly and do not merit genetic testing due to the high frequency of sporadic cases. 7 , 8 The second group, which includes our patient from Case 1, consists of patients with preaxial polydactyly plus additional limb malformations. These patients are often found to have mutations in the GLI3 gene, which codes for a downstream mediator of the Sonic hedgehog (Shh) cell signaling pathway.…”

Clinical Genetics of Polydactyly: An Updated Review

“…Heptadactyly or hexadactyly is also a type of thumb polydactyly in which triplication of thumb occurs, resulting in seven digits ( Zuidam et al, 2008 ). Familial PPD type 1 only shows autosomal dominant inheritance pattern with reduced penetrance ( Castilla et al, 1973 : Orioli and Castilla, 1999 ; Burger et al, 2018 ). Preaxial type 1 polydactyly is caused by sequence variants in the sonic hedgehog (SHH) enhancer, called zone of polarizing activity (ZPA) regulatory sequence ( ZRS ) ( Lettice et al, 2002 ; Wieczorek et al, 2010 ; Perez-Lopez et al, 2018 ).…”

“…In polysyndactyly (MIM 174700) the thumb is duplicated mildly, the distal phalanxes show radial deviation or with a broad and bifid thumb. Syndactyly of third and fourth fingers is rarely present ( Temtamy and McKusick, 1978 ; Burger et al, 2018 ). In the feet, the first toe shows polydactyly, and the first metacarpal is tibially deviated and short.…”