Radiographic features of the skeleton in disorders of post-squalene cholesterol biosynthesis

Pediatr Radiol. 2015 Jul;45(7):965-76. doi: 10.1007/s00247-014-3257-9. Epub 2015 Feb 3.


Disorders of post-squalene cholesterol biosynthesis are inborn errors of metabolism characterised by multiple congenital abnormalities, including significant skeletal involvement. The most frequent and best-characterised example is the Smith-Lemli-Opitz syndrome. Nine other disorders are known, namely autosomal-recessive Antley-Bixler syndrome, Greenberg dysplasia, X-linked dominant chondrodysplasia punctata, X-linked recessive male emopamil-binding protein deficiency, CHILD syndrome, CK syndrome, sterol C4 methyloxidase-like deficiency, desmosterolosis and lathosterolosis. This study provides an overview of the radiologic features observed in these diseases. A common pattern of limb abnormalities is recognisable, including polydactyly, which is typically post-axial and rarely interdigital and can involve all four limbs, and syndactyly of the toes. Chondrodysplasia punctata is specifically associated with a subgroup of disorders of cholesterol biosynthesis (Greenberg dysplasia, CHILD syndrome, X-linked dominant chondrodysplasia punctata, male emopamil-binding protein deficiency). The possible occurrence of epiphyseal stippling in the Smith-Lemli-Opitz syndrome, initially reported, does not appear to be confirmed. Stippling is also associated with other congenital disorders such as chromosomal abnormalities, brachytelephalangic chondrodysplasia punctata (X-linked recessive chondrodysplasia punctata, disruptions of vitamin K metabolism, maternal autoimmune diseases), rhizomelic chondrodysplasia punctata (peroxisomal disorders) and lysosomal storage disorders. In the differential diagnosis of epiphyseal stippling, a moth-eaten appearance of bones, asymmetry, or presence of a common pattern of limb abnormalities indicate inborn errors of cholesterol biosynthesis. We highlight the specific differentiating radiologic features of disorders of post-squalene cholesterol biosynthesis.

Publication types

  • Review

MeSH terms

  • Adult
  • Child
  • Child, Preschool
  • Cholesterol / biosynthesis*
  • Female
  • Humans
  • Infant
  • Lipid Metabolism, Inborn Errors / complications*
  • Male
  • Musculoskeletal Abnormalities / complications*
  • Musculoskeletal Abnormalities / diagnostic imaging*
  • Musculoskeletal System / diagnostic imaging*
  • Pregnancy
  • Prenatal Diagnosis
  • Radiography
  • Young Adult


  • Cholesterol