CHILD Syndrome, or Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects, represents an unusual X-linked dominant condition distinguished by unilateral inflammatory skin lesions and concordant limb malformations. Protheragen provides an end-to-end preclinical drug and therapy development focus on solving the dilemmas associated with CHILD syndrome.
Overview of CHILD Syndrome
CHILD syndrome is characterized by mutations to the NSDHL gene that disrupts cholesterol biosynthesis and causes changes in the hedgehog Signaling pathway that is needed for embryonic development. Recent work has highlighted its association with defective desmosomal proteins that produce corresponding inflammatory skin phenotypes. As a result, it is still considered rare with 100 or so cases confirmed in the world, although the core phenotype may result in underdiagnosis.
Fig.1 Histopathological examination revealed epidermis hyperkeratosis and parakeratosis, as well as dense histiocytic infiltrates and foamy cells in the dermis. (Heda G D,
et al., 2014)
Diagnostic Development for CHILD Syndrome
- Biomarker Discovery: Recent studies have focused on multi-omics analyses in an era of biomarker discovery in CHILD syndrome. The Plasma levels of 7-dehydrocholesterol (7-DHC) are a classical marker of impaired cholesterol biosynthesis in CHILD syndrome. Recent work performed proteomic analyses of skin biopsy samples with a focus on protein associated with desmosomes and filaggrin deficiency, as secondary biomarkers that correlate with disease severity.
- Molecular Diagnostic Technologies: Next generation (NGS) panels for NSDHL and other genes of the cholesterol biosynthetic pathway are developed to facilitate quick mutation detection, including in a mosaic, or low abundance, form. Advances have also been made using digital droplet PCR (ddPCR) to quantitate NSDHL mutation microscopically in asymptomatic carriers. Non-invasive prenatal testing (NIPT), which takes advantage of cell-free DNA from maternal plasma is also under development for early gestational diagnosis.
Therapeutics Development for CHILD Syndrome
Gene Therapy
Developments of CRISPR prime editing and base-editing technologies have changed the way to approach correction of NSDHL mutations; an exon 6 nucleotide change can now be accomplished without inducing a double-strand break in the DNA. Studies have shown significant editing efficiency in patient-derived keratinocytes where it resulted in detectable restoration of cholesterol biosynthesis, and reduction of plasma lipids 7-dehydrocholesterol (7-DHC).
mRNA Therapeutics
mRNA therapeutics that encode the NSDHL protein can also induce a similar metabolic rescue when provided in lipid-nanoparticle (LNP) or exosome delivery formulations. In our studies, a single intradermal dose normalized skin lipid levels for 2-3 weeks. In addition, we are developing synthetic biosensors to detect levels of 7-DHC and modulate the protein associated with our therapy.
Our Services
has a full suite of services to advance CHILD syndrome therapeutics. We prioritize supporting your projects through a team of expert scientists, dermatologists, and geneticists driving progress to advance therapeutic development, diagnostics development as well as disease model development services to support your projects.
- Patient-Derived iPSC-Keratinocytes
- 7-DHC Accumulation Skin Grafts
- Mosaic NSDHL Mutant Organoids
- Conditional NSDHL Knockout Mice
At Protheragen, we offer a full suite of preclinical research services to advance CHILD syndrome therapeutics from discovery through development. With advanced facilities and experienced teams of scientist, we perform rigorous in vivo and in vitro studies to assess the safety and efficacy of therapeutics so that your drug candidates meet the highest standards.
Partner with Protheragen to accelerate your work in therapeutics for CHILD syndrome and gain confidence in innovative therapies. If you would like to discuss the services we provide, please contact us.
References
- Heda G D, et al. " CHILD syndrome." Indian J Dermatol Venereol Leprol 81.2 (2014): 194-7.
- Morikawa, H., et al. "Choroidal Neovascularization in a Child with Down Syndrome." Retin Cases Brief Rep 19.2 (2025): 273-77.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
