A registry of achondroplasia: a 6-year experience from the Czechia and Slovak Republic
Abstract Background Achondroplasia (ACH) is one of the most prevalent genetic forms of short-limbed skeletal dysplasia, caused by gain-of-function mutations in the receptor tyrosine kinase FGFR3. In August 2021, the C-type natriuretic peptide (CNP) analog vosoritide was approved for the treatment of...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-06-01
|
| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-022-02374-x |
| _version_ | 1818236856870895616 |
|---|---|
| author | Martin Pesl Hana Verescakova Linda Skutkova Jana Strenkova Pavel Krejci |
| author_facet | Martin Pesl Hana Verescakova Linda Skutkova Jana Strenkova Pavel Krejci |
| author_sort | Martin Pesl |
| collection | DOAJ |
| description | Abstract Background Achondroplasia (ACH) is one of the most prevalent genetic forms of short-limbed skeletal dysplasia, caused by gain-of-function mutations in the receptor tyrosine kinase FGFR3. In August 2021, the C-type natriuretic peptide (CNP) analog vosoritide was approved for the treatment of ACH. A total of six other inhibitors of FGFR3 signaling are currently undergoing clinical evaluation for ACH. This progress creates an opportunity for children with ACH, who may gain early access to the treatment by entering clinical trials before the closure of their epiphyseal growth plates and cessation of growth. Pathophysiology associated with the ACH, however, demands a long observational period before admission to the interventional trial. Public patient registries can facilitate the process by identification of patients suitable for treatment and collecting the data necessary for the trial entry. Results In 2015, we established the prospective ACH registry in the Czechia and the Slovak Republic ( http://www.achondroplasia-registry.cz ). Patient data is collected through pediatric practitioners and other relevant specialists. After informed consent is given, the data is entered to the online TrialDB system and stored in the Oracle 9i database. The initial cohort included 51 ACH children (average age 8.5 years, range 3 months to 14 years). The frequency of selected neurological, orthopedic, or ORL diagnoses is also recorded. In 2015–2021, a total of 89 measurements of heights, weights, and other parameters were collected. The individual average growth rate was calculated and showed values without exception in the lower decile for the appropriate age. Evidence of paternal age effect was found, with 58.7% of ACH fathers older than the general average paternal age and 43.5% of fathers older by two or more years. One ACH patient had orthopedic limb extension and one patient received growth hormone therapy. Low blood pressure or renal impairment were not found in any patient. Conclusion The registry collected the clinical information of 51 pediatric ACH patients during its 6 years of existence, corresponding to ~ 60% of ACH patients living in the Czechia and Slovak Republic. The registry continues to collect ACH patient data with annual frequency to monitor the growth and other parameters in preparation for future therapy. |
| first_indexed | 2024-12-12T12:16:31Z |
| format | Article |
| id | doaj.art-a866550359a44a28a60a8e769699d833 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-12T12:16:31Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-a866550359a44a28a60a8e769699d8332022-12-22T00:24:46ZengBMCOrphanet Journal of Rare Diseases1750-11722022-06-011711710.1186/s13023-022-02374-xA registry of achondroplasia: a 6-year experience from the Czechia and Slovak RepublicMartin Pesl0Hana Verescakova1Linda Skutkova2Jana Strenkova3Pavel Krejci4Department of Biology, Faculty of Medicine, Masaryk UniversityDepartment of Biology, Faculty of Medicine, Masaryk UniversityDepartment of Pediatrics, University Hospital BrnoInstitute of Biostatistics and Analyses, Masaryk UniversityDepartment of Biology, Faculty of Medicine, Masaryk UniversityAbstract Background Achondroplasia (ACH) is one of the most prevalent genetic forms of short-limbed skeletal dysplasia, caused by gain-of-function mutations in the receptor tyrosine kinase FGFR3. In August 2021, the C-type natriuretic peptide (CNP) analog vosoritide was approved for the treatment of ACH. A total of six other inhibitors of FGFR3 signaling are currently undergoing clinical evaluation for ACH. This progress creates an opportunity for children with ACH, who may gain early access to the treatment by entering clinical trials before the closure of their epiphyseal growth plates and cessation of growth. Pathophysiology associated with the ACH, however, demands a long observational period before admission to the interventional trial. Public patient registries can facilitate the process by identification of patients suitable for treatment and collecting the data necessary for the trial entry. Results In 2015, we established the prospective ACH registry in the Czechia and the Slovak Republic ( http://www.achondroplasia-registry.cz ). Patient data is collected through pediatric practitioners and other relevant specialists. After informed consent is given, the data is entered to the online TrialDB system and stored in the Oracle 9i database. The initial cohort included 51 ACH children (average age 8.5 years, range 3 months to 14 years). The frequency of selected neurological, orthopedic, or ORL diagnoses is also recorded. In 2015–2021, a total of 89 measurements of heights, weights, and other parameters were collected. The individual average growth rate was calculated and showed values without exception in the lower decile for the appropriate age. Evidence of paternal age effect was found, with 58.7% of ACH fathers older than the general average paternal age and 43.5% of fathers older by two or more years. One ACH patient had orthopedic limb extension and one patient received growth hormone therapy. Low blood pressure or renal impairment were not found in any patient. Conclusion The registry collected the clinical information of 51 pediatric ACH patients during its 6 years of existence, corresponding to ~ 60% of ACH patients living in the Czechia and Slovak Republic. The registry continues to collect ACH patient data with annual frequency to monitor the growth and other parameters in preparation for future therapy.https://doi.org/10.1186/s13023-022-02374-xSkeletal dysplasiaAchondroplasiaFGFR3TreatmentRegistryReACH |
| spellingShingle | Martin Pesl Hana Verescakova Linda Skutkova Jana Strenkova Pavel Krejci A registry of achondroplasia: a 6-year experience from the Czechia and Slovak Republic Orphanet Journal of Rare Diseases Skeletal dysplasia Achondroplasia FGFR3 Treatment Registry ReACH |
| title | A registry of achondroplasia: a 6-year experience from the Czechia and Slovak Republic |
| title_full | A registry of achondroplasia: a 6-year experience from the Czechia and Slovak Republic |
| title_fullStr | A registry of achondroplasia: a 6-year experience from the Czechia and Slovak Republic |
| title_full_unstemmed | A registry of achondroplasia: a 6-year experience from the Czechia and Slovak Republic |
| title_short | A registry of achondroplasia: a 6-year experience from the Czechia and Slovak Republic |
| title_sort | registry of achondroplasia a 6 year experience from the czechia and slovak republic |
| topic | Skeletal dysplasia Achondroplasia FGFR3 Treatment Registry ReACH |
| url | https://doi.org/10.1186/s13023-022-02374-x |
| work_keys_str_mv | AT martinpesl aregistryofachondroplasiaa6yearexperiencefromtheczechiaandslovakrepublic AT hanaverescakova aregistryofachondroplasiaa6yearexperiencefromtheczechiaandslovakrepublic AT lindaskutkova aregistryofachondroplasiaa6yearexperiencefromtheczechiaandslovakrepublic AT janastrenkova aregistryofachondroplasiaa6yearexperiencefromtheczechiaandslovakrepublic AT pavelkrejci aregistryofachondroplasiaa6yearexperiencefromtheczechiaandslovakrepublic AT martinpesl registryofachondroplasiaa6yearexperiencefromtheczechiaandslovakrepublic AT hanaverescakova registryofachondroplasiaa6yearexperiencefromtheczechiaandslovakrepublic AT lindaskutkova registryofachondroplasiaa6yearexperiencefromtheczechiaandslovakrepublic AT janastrenkova registryofachondroplasiaa6yearexperiencefromtheczechiaandslovakrepublic AT pavelkrejci registryofachondroplasiaa6yearexperiencefromtheczechiaandslovakrepublic |