Short-rib thoracic dysplasia 2 with or without polydactyly (SRTD2; MIM 611263), SRTD3 (MIM 613091), SRTD4 (MIM 613819), SRTD5 (MIM 614376), SRTD6 (MIM 263520), SRTD7 (MIM 614091) and SRTD8 (MIM 615503) display similar clinical, radiological and histological features.  All of these disorders are ciliopathies characterized by short ribs with a narrow thorax, short long bones and a trident appearance of the acetabular roof with or without polydactyly.  Extra skeletal findings may include anomalies of the brain, eye, genitalia, heart, intestines, kidney, liver, and pancreas. SRTDs are among the most common autosomal recessive osteochondrodysplasias.

SRTD2 is caused by mutations in the IFT80 gene, which codes for intraflagellar transport protein 80 homolog.  IFT80 is a component of the intraflagellar transport complex B, which is essential for the development and maintenance of motile and sensory cilia.  

SRTD3 is caused by mutations in the cytoplasmic dynein 2 heavy chain 1 gene (DYNC2H1), which codes for a component of the cytoplasmic dynein complex.  Specifically, it codes for the “motor” responsible for retrograde intraflagellar transport from the cilia tip to basal body.

SRTD4 is caused by mutations in the tetratricopeptide repeat protein 21B gene (TTC21B).  This gene encodes an axonemal protein required for the retrograde intraflagellar transport. 

SRTD5 is caused by mutations in the WDR19 gene, which codes for WD repeat-containing protein 19.  It is involved in retrograde ciliary transport. 

SRTD6 is caused by mutations in the NEK1 gene.  A digenic diallelic mode of inheritance has also been proposed because of the identification of heterozygous mutations in the NEK1 and DYNC2H1 genes. NEK1 encodes serine/threonine-protein kinase Nek1 with numerous proposed roles. It seems to have a critical role in cell-cycle associated ciliogenesis, DNA double strand repair and neuronal development.

SRTD7 is caused by mutations in the WDR35 gene, which encodes WD repeat-containing protein 35.  Mutations result in the abrogation or interruption of retrograde transport.

SRTD8 is caused by mutations in the WDR60 gene, which codes for the WD repeat-containing protein 60. The function of WDR60 is poorly characterized but fibroblast derived from an affected individual displayed a defect in ciliogenesis.