Polydactyly and Syndactyly Panel

Congenital polydactyly (also known as hyperdactyly or hexadactyly) is defined as extra fingers or toes. It is one of the most common limb birth defects with an estimated incidence of one in 700–1,000 live births (Umair et al. 2018. PubMed ID: 30459804; Malik. 2014. PubMed ID: 24020795; Ahmed et al. 2017. PubMed ID: 29263957). It is mainly a failure in the control of digit number at cellular and developmental levels (Malik. 2014. PubMed ID: 24020795). It may manifest isolated (non-syndromic) or as part of many syndromic conditions. Polydactyly can be further divided as preaxial (radial), central (axial), and postaxial (ulnar) (Umair et al. 2018. PubMed ID: 30459804; Malik. 2014. PubMed ID: 24020795).

Congenital syndactyly is defined as joined fingers or toes by soft tissue or by bone. Syndactyly has an estimated incidence of 1 in 2,000 to 3,000 live births. This condition is caused by failed separation during embryonic development (Ahmed et al. 2017. PubMed ID: 29263957; Tonkin. 2009. PubMed ID: 19380059). It may manifest as an isolated (non-syndromic) case or as part of more than 300 syndromic conditions. Syndactyly can present as unilateral/bilateral, finger/toe; complete or partial (Malik. 2012. PubMed ID: 22333904; Deng and Tan. 2015. PubMed ID: 26069458; Tonkin. 2009. PubMed ID: 19380059).

Molecular genetic testing is advantageous to establish an accurate diagnosis for individuals with a variety of syndactyly and polydactyly conditions. Co-features of many of these conditions may require medical attention.

This panel combines genes associated with a variety of genetic syndactyly and polydactyly disorders that have been identified through literature, OMIM, and HGMD searches. The patterns of inheritance can be autosomal dominant (AD), autosomal recessive (AR) or X-linked (XL) (Al-Qattan. 2019. PubMed ID: 31637260; Umair et al. 2018. PubMed ID: 30459804; Malik. 2014. PubMed ID: 24020795). Examples include Split-hand/foot malformation (also known as ectrodactyly), FGFR2-related conditions (Apert syndrome, LADD syndrome, and Saethre-Chotzen syndrome), HOXD13-related Syndactyly/polydactyly, Robinow syndrome, TP63-related conditions, Lenz-Majewski hyperostotic dwarfism, Temtamy preaxial brachydactyly syndrome, Squalene synthase deficiency, Filippi syndrome, Roberts syndrome, Metacarpal 4-5 fusion, Bartsocas-Pappas syndrome, Cenani-Lenz syndactyly syndrome, GLI3-related conditions, GLI1-related polydactyly, DHCR7-related Smith-Lemli-Opitz syndrome, and Acrocallosal syndrome.

See individual gene test descriptions for information on molecular biology of gene products, and spectra of pathogenic variants.

In one study, pathogenic variants were found in 18% (36/199) of patients with a genetic etiology of congenital upper limb defects. Among them, 13/199 cases had a copy number variation at the chromosomal level, and 23/199 cases were found to have a pathogenic variant involving a single nucleotide substitution, or small deletion/insertion (Carli et al. 2013. PubMed ID: 24343878).

This test is able to detect both large copy number variation (large deletions and insertions) (CNV) as well as smaller sequence variants (SNVs) with high analytical sensitivity.

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 97.4% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).