Short-rib thoracic dysplasia with or without polydactyly

SRTD is an umbrella term for several formerly distinct syndromes that share overlapping genetic origins. Common conditions that fall under this group include Jeune Syndrome (aka asphyxiating thoracic dystrophy), short-rib polydactyly syndrome (SRPS), Ellis-van Creveld Syndrome (EVC), and Mainzer-Saldino syndrome.

The SRTD skeletal phenotype comprises abnormally short ribs, a narrow thorax, shortened tubular bones in the arms and legs, and potential postaxial polydactyly (extra digits). Respiratory insufficiency is due to a severely restricted thoracic cage, often leading to life-threatening breathing problems, which can be fatal in the neonatal period. Multisystem features are common and include renal involvement (cystic dysplasia, nephronophthisis, and progressive kidney disease, particularly in IFT140– and WDR19-related forms), congenital hepatic fibrosis with biliary involvement, retinal dystrophy in the Mainzer-Saldino variant, and craniofacial or ectodermal features overlapping with cranioectodermal dysplasia. Inter- and intra-familial variability in age of onset, severity, and organ involvement is marked, with prenatal-onset severe forms contrasting with milder phenotypes diagnosed in childhood or adolescence.

The estimated prevalence for SRTD as an overall group is approximately 1 in 100,000 to 1 in 130,000 live births.

More than 30 genes have been associated with short-rib thoracic dysplasia, the most frequently implicated being DYNC2H1, IFT140, WDR19, WDR34, and WDR60. The condition is caused by biallelic germline pathogenic variants in genes encoding components of the primary-cilium intraflagellar transport machinery, disrupting ciliogenesis as well as Hedgehog and Wnt signalling required for skeletal and visceral development.

Diagnosis is established primarily by molecular genetic testing. The condition is typically suggested by characteristic prenatal or postnatal skeletal radiographic findings: a narrow bell-shaped thorax with short horizontal ribs, a trident acetabular roof, handlebar clavicles, and variable postaxial polydactyly.