Rapp-Hodgkin syndrome (RHS) is a rare condition that combines the features of ectodermal dysplasia with some form of palatal abnormality. Protheragen develops preclinical studies using molecular pathology and therapeutic innovation focusing on TP63 pathology on RHS.
Introduction to Rapp-Hodgkin Syndrome
Rapp-Hodgkin syndrome is an autosomal dominant hereditary condition resulting from a heterozygous TP63 mutation with a global prevalence of around: 1/500000. Ectodermal dysplasia, orofacial clefts such as cleft palate, and urogenital defects constitute some of the RHS phenomena. Unlike LMS features, RHS shows marked presence of craniofacial defects but no limb anomalies.
Pathogenesis of Rapp-Hodgkin Syndrome
- TP63 Dysregulation: Dysregulated endocrinologist caused by mutations in TP63 result in loss of p63 dependent maintenance and morphogenesis of epidermal stem cells. This results in inadequate and palatal sculpting, immature hair follicles, and, and inadequate palatal structure formations.
- Ectodermal Defects: Alopecia, dystrophic nails, and hyperhidrosis all provide evidence for insufficient p63. Aberrant signaling via FGF, Notch, in addition to loss of cleft palate paves the way for even further deformation on the palate.
- Secondary Complications: Due to flawed mucosal barriers chronic infections, and dental agenesis along with psychosocial craniofacial distortions all serve embellishments for these common comorbid conditions.
Fig.1 TP63 mutations identified inTap63‐α. (Hori
et al., 2023)
Therapeutics Development for Rapp-Hodgkin Syndrome
The development of therapeutic strategies for RHS is primarily centered on symptom management. There are opportunities for therapies that are more targeted and gene-based, but such prospects are at the early stages of investigation. As research progresses on the role of the TP63 gene in these syndromes, specific therapeutic approaches may become feasible.
Table.1 Therapies for Rapp-Hodgkin Syndrome.
| Therapeutic Strategy |
Target / Intervention |
Key Findings / Rationale |
Development Stage |
| Targeted Therapies |
Modulation of TP63 pathway |
Correcting/compensating for dysfunctional TP63 protein. Highly theoretical. |
Preclinical |
| Addressing downstream signaling pathways affected by TP63 dysfunction |
Targeting disrupted pathways (e.g., cell proliferation, differentiation). |
Preclinical |
| Gene Therapy |
Delivery of a functional TP63 gene or gene editing to correct the mutation |
Addresses the underlying genetic defect; potential for disease modification/cure. |
Preclinical |
| Small Molecule Approaches |
Identifying compounds that can rescue or bypass the effects of the TP63 mutation |
Improves mutant TP63 function or activates compensatory pathways. |
Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen provides the complete service of developing therapies for rare skin diseases such as Rapp-Hodgkin syndrome. Our specialists, including scientists, dermatologists, and geneticists, formulate therapeutic and disease model to support all research project phases.
Therapeutic Development Platforms for Rapp-Hodgkin Syndrome
Disease Model Development for Rapp-Hodgkin Syndrome
Protheragen also possesses custom 2D cell models and 3D skin models that mimic RHS etiology—in which p63 signaling perturbations, craniofacial morphogenesis aberrations, and ectodermal barrier breaches occur—along with animal models exhibiting key Rapp-Hodgkin syndrome features, making them ideal for therapeutic testing.
- Patient-Derived TP63-Mutant Keratinocytes
- TP63 Haploinsufficiency Models
- RHS Epidermal-Mucosal Organoid
- TP63-Mutant Reconstructed Human Epidermis
- Conditional Epithelial Tp63 Knockout Mice
- Humanized TP63 R304Q Knock-In Mice
- Tp63+/- Zebrafish Model
- Tp63ΔSAM/ΔSAM Homozygous Mouse Model
Protheragen specializes in preclinical research services. Using integrated discovery platforms, we accelerate therapeutic development for rare cutaneous disorders like Rapp-Hodgkin syndrome. Our innovative proprietary disease models alongside drug safety evaluation to DMPK services facilitate the progression from target validation to IND enabling studies seamlessly. If you are interested in our services, please feel free to contact us.
References
- Hori, A., et al. "A Novel Tp63 Variant in a Patient with Ankyloblepharon-Ectodermal Defect-Cleft Lip/Palate Syndrome and Rapp-Hodgkin Syndrome-Like Ectodermal Dysplasia." Hum Genome Var 9.1 (2022): 17.
- Marialva, J., et al. "Peri-Operative Management of a Patient with an Ectodermal Dysplasia (Rapp-Hodgkin) Syndrome." Anaesth Rep 11.1 (2023): e12210.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
