Polydactyly 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  1.6–10.7/1,000 or 0.3–3.6/1000 (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 polydactyly (axial), and postaxial (ulnar) polydactyly (Umair et al. 2018. PubMed ID: 30459804; Malik. 2014. PubMed ID: 24020795).

Molecular genetic testing is advantageous to establish an accurate diagnosis for individuals with a variety of polydactyly conditions.

This panel includes genes associated with polydactyly 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) (Umair et al. 2018. PubMed ID: 30459804; Malik. 2014. PubMed ID: 24020795).

This panel tests for many congenital non-syndromic and syndromic related polydactyly conditions such as GLI3-related conditions, GLI1-related polydactyly,  HOXD13-related polydactyly, Joubert syndrome, Orofaciodigital syndrome, DHCR7-related Smith-Lemli-Opitz syndrome, Short-rib thoracic dysplasia 3 with or without polydactyly, LADD 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 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 98.5% 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).