Congenital Limb Malformation Panel

Congenital limb malformation refers to both gross reduction defects and more subtle alterations in the number, length, and anatomy of the legs, arms, and digits. The prevalence is ~ 1 in 500 to 1 in 1,000 live births (Wilkie. 2003. PubMed ID: 12587917). Congenital limb malformation includes many conditions such as: preaxial/postaxial polydactyly of the foot/hand (Burger et al. 2017. PubMed ID: 28946786), brachydactyly, and limb hypoplasia-reduction (Bonafe et al. 2015. PubMed ID: 26394607).

This panel includes 72 genes associated with a variety of genetic congenital limb malformations (Wilkie. 2003. PubMed ID: 12587917; Bonafe et al. 2015. PubMed ID: 26394607). Genetic limb malformations are genetically heterogenous and can be inherited in an autosomal dominant (AD), autosomal recessive (AR), and X-linked (XL) manner.

This panel offers testing for the following and many other conditions: Brachydactyly, Ectrodactyly, Polydactyly, Syndactyly, Symphalangism, Townes-Brocks branchiootorenal-like syndrome, Duane-radial ray syndrome, Fanconi anemia, Pallister-Hall syndrome, Split-hand/foot malformation, some subtypes of Meckel syndrome, Holt-Oram syndrome, Robinow syndrome, Liebenberg syndrome, TP63-related conditions, Liebenberg syndrome, Keutel Syndrome, Smith McCort Dysplasia, Yunis-Varon Syndrome, Camptomelic Dysplasia, and Feingold syndrome 1.

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 Anomalies. Among them, 13/199 cases had a copy number variation on 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 performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 99.5% 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).

Some genes have multiple copies in the haploid genome. In these cases, we may only analyze a portion of these genes.

Other genes without full coverage include, but may not be limited to: CEP290, CHSY1, DOCK6, FMN1, LRP4, NIPBL, NOTCH1, FANCD2, SALL1, SALL4, SHH, SF3B4, FBXW4, SHH, SOX9, RPGRIP1L, and RBM8A. A full list of regions not covered by NGS or Sanger sequencing is available upon request.

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).