CHILD syndrome: A modified pathogenesis-targeted therapeutic approach

Am J Med Genet A. 2018 Mar;176(3):733-738. doi: 10.1002/ajmg.a.38619. Epub 2018 Feb 2.


Congenital Hemidysplasia with Ichthyosiform nevus and Limb Defects (CHILD syndrome) is a rare X-linked dominant genodermatosis caused by mutations in the NAD(P) dependent steroid dehydrogenase-like protein gene. Its defect leads to accumulation of toxic metabolic intermediates upstream from the pathway block and to the deficiency of bulk cholesterol, probably leading to altered keratinocyte membrane function, resulting in the phenotype seen in CHILD syndrome. Symptomatic treatment using emollients and retinoids to reduce scaling has long been used until recently, whereby new therapeutic means based on the pathogenesis-targeted therapy have been developed. We subsequently chose to use the same pathogenesis-based therapy using a 2% cholesterol and 2% lovastatin cream with or without glycolic acid in two of our patients. Improvement in CHILD skin lesions was seen as early as 4 weeks after initiation. The addition of glycolic acid helped improve the penetrance of the cholesterol and lovastatin cream into the thick waxy scales. Our study confirms the efficacy of the pathogenesis-targeted therapy and introduces the possibility of modifying its formula by adding glycolic acid in order to improve the treatment.

Keywords: NSDHL; cholesterol; glycolic acid; statin.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxysteroid Dehydrogenases / genetics
  • Abnormalities, Multiple / diagnosis*
  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / therapy
  • Biopsy
  • Child
  • Cholesterol / administration & dosage
  • Female
  • Genetic Diseases, X-Linked / diagnosis*
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Diseases, X-Linked / therapy
  • Humans
  • Ichthyosiform Erythroderma, Congenital / diagnosis*
  • Ichthyosiform Erythroderma, Congenital / genetics*
  • Ichthyosiform Erythroderma, Congenital / therapy
  • Limb Deformities, Congenital / diagnosis*
  • Limb Deformities, Congenital / genetics*
  • Limb Deformities, Congenital / therapy
  • Lovastatin / administration & dosage
  • Mutation
  • Phenotype
  • Skin / pathology
  • Treatment Outcome


  • Cholesterol
  • Lovastatin
  • 3-Hydroxysteroid Dehydrogenases
  • Nsdhl protein, human

Supplementary concepts

  • Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects