Short rib-polydactyly syndrome, type III (SRPS)

Short rib-polydactyly syndrome, type III and asphyxiating thoracic dystrophy 2 and 3

Short rib-polydactyly syndrome, type III (SRPS, type III; MIM 263510) and asphyxiating thoracic dystrophy 2 and 3 (ATD2; MIM 611263 and ATD3; MIM 613091) are autosomal recessive osteochondrodysplasias that display similar clinical, radiological and histological features.  All of these disorders are characterized by short ribs with a narrow thorax, short long bones and polydactyly.  The short-rib polydactyly syndromes and ATD are among the most common autosomal recessive osteochondrodysplasias.

SRPS, type III, or Verma-Naumoff syndrome, is considered to be more severe than ATD and is characterized by a severely narrow thorax and neonatal asphyxia.  SRPS, type III may also be characterized by a distinct corticomedullary demarcation of the long bones, metaphyseal spikes, ambiguous genitalia, cystic renal disease, and various cranial, gastrointestinal and brain abnormalities.

Although ATD2 and ATD3 are typically fatal during the first year of life, some patients have survived to adulthood.  Additional findings in patients with ATD2/ATD3 may include trident shaped acetabular roofs, retinal degeneration, cystic renal disease and occasional liver involvement.  The ATD phenotype is genetically heterogenous as ATD1 (MIM 208500) has been linked to a locus at 15q13.

Mutations in the dynein, cytoplasmic 2, heavy chain 1 gene (DYNC2H1) have been described in some cases of SRPS, type III and ATD3.  The DYNC2H1 gene 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.  Mutations in the intraflagellar transport 80 homolog (Chlamydomonas) gene (IFT80) have been described in patients with ATD2.  The IFT80 gene codes for an intraflagellar transport protein involved in anterograde intraflagellar transport.