Call for collaborative clinical research

ERN BOND aims to favour research collaborations among network members to rapidly build up clinical series for rare skeletal disorders, to better delineate the clinical spectrum, natural history, and clinical management of these conditions.

A permanent call of collaborative clinical research is therefore open to clinicians working in the ambit of ERN BOND diseases. The call list will be disseminated through the monthly newsletter.

Clinical trial in adults with distal arthrogryposis type 5 - PIEZO2 gain of function variants.

Title Clinical trial in adults with distal arthrogryposis type 5 – PIEZO2 gain of function variants.
Target PIEZO2 (MIM#613629) / Distal arthrogryposis type 5 (ORPHA:1154)
Summary As national reference centre for arthrorgyposis multiplex congenita (AMC), we have established a therapeutic trial protocol for adult individuals with distal arthrogryposis type 5 (DA5), caused by hetorozygous gain-of-function variants in the PIEZO2 gene. PIEZO2 encodes a non-selective cation channel expressed in peripheral somatosensory afferent neurons of the dorsal root ganglia. Pain is a major complication and remains poorly controlled by conventional analgesic treatments.
The goal of our study is to test the efficacy in controlling pain of a repurposed antagonist of voltage-gated sodium channels. Secondary endpoints include treatment tolerance, impact of the treatment on the use of co-analgesics and quality of life.
In order to extend the number of individuals and submit to the ERDERA Clinical Trial call, we would like to reach out to other clinicians/ centres in charge of adult individuals affected by PIEZO2 related DA and potentially interested in participating.
Submission Deadline 31/12/2026
Other specific requirements  None
Contact person  DIETERICH Klaus
Institution  Department of medical genetics, CHU de Grenoble, France
Contact

KEUTEL SYNDROME: Natural history

Title KEUTEL SYNDROME: Natural history
Target ORPHA85202
Summary Keutel syndrome (KS) as a scarce autosomal recessive disorder is characterized by hearing loss, multiple peripheral pulmonary stenoses, abnormal cartilage calcification, and morphological defects including midface hypoplasia and brachytelephalangism. Our aim is to better describe the natural history, by collecting detailed clinical data
Submission Deadline 15/03/2027
Other specific requirements  None
Contact person  CORMIER-DAIRE Valerie
Institution  Genomic medicine for rare diseases, nekcer hospital, Paris
Contact

Expanding the phenotypic spectrum of biallelic GHSR variants

Title Expanding the phenotypic spectrum of biallelic GHSR variants
Target 601898, GHSR
Summary Biallelic variants in GHSR, encoding the ghrelin receptor, are extremely rare and remain poorly characterized, with only a limited number of patients reported worldwide. We have identified two patients with short stature, due to a homozygous GHSR variant (NM_198407.2.611C>A), currently followed at Necker–Enfants Malades Hospital, Paris. Both patients present with impaired growth and GH deficiency, associated with low IGF-1 levels and delayed bone age; one patient also developed obesity.
We propose a European collaboration to identify additional patients with biallelic GHSR variants. We aim to collect and analyze genomic, and detailed phenotypic data including pre- and postnatal growth, GH–IGF-1 axis abnormalities, response to GH treatment, as well as any associated feature. Please get in touch if you have any patients whom you would be interested in contributing to this collaborative study and joint publication.
Submission Deadline 01/09/2027
Other specific requirements  None
Contact person  Dr Lucile Riera-Navarro / Pr Valérie Cormier-Daire
Institution  Hôpital Necker-Enfants Malade
Contact

Maffucci syndrome and adrenal cortex tumor

Title Maffucci syndrome and adrenal cortex tumor
Target Maffucci syndrome (ORPHA:163634)
Summary Adrenal cortex tumors have been reported in some patients affected by Maffucci syndrome, although the etiopathological link between these two entities is unknown. We are collecting more cases to verify this association and to determine if a routine evaluation for involvement of the adrenal cortex should be introduced in the clinical follow up.
Submission Deadline 30/06/2025
Other specific requirements  None
Contact person  Alice Moroni
Institution  Istituto Ortopedico Rizzoli, Bologna, Italy
Contact

Rasopathies and tenosynovial giant cell tumor

Title  Rasopathies and tenosynovial giant cell tumor
Target Rasopathies (ORPHA:536391); Noonan syndrome (ORPHA:648); Tenosynovial giant cell tumor (ORPHA:66627)
Summary Tenosynovial giant cell tumor (or pigmented villonodular synovitis, PVNS) has been previously reported in Noonan syndrome; however, the exact prevalence of this association is unknown. We are collecting data from patients to determine whether the presentation of PVNS and its clinical management differ in individuals affected by Noonan syndrome. Additionally, we aim to investigate whether other RASopathies also pose a higher risk for this rare orthopedic complication.
Submission Deadline 30/06/2025
Other specific requirements None
Contact person  Alice Moroni
Institution Istituto Ortopedico Rizzoli, Bologna, Italy
Contact

A cohort of patients with Acrodysostosis: Clinical and molecular characterization

Title  A cohort of patients with Acrodysostosis: Clinical and molecular characterization
Target OMIM #101800 and OMIM #614613 or ORPHA code 950
Summary Acrodysostosis is rare skeletal dysplasia characterized by short stature, severe brachydactyly, facial dysostosis with nasal hypoplasia, cone-shaped epiphyses, hormonal resistance (usually thyrotropin or parathyroid hormone), and intellectual disability (ORPHA:950). Being a rare disease with less than 80 cases described worldwide, this study aims to complete the spectrum of clinical presentations, strengthen or document new genotype-phenotype correlations, and describe how this condition is managed. We are looking for patients with mutations in the PRKAR1A (iPPSD4) and the PDE4D (iPPSD5) genes to perform a retrospective clinical and molecular data analysis. The data we want to collect includes the patient’s phenotype, genotype, comorbidities, and management. This investigation is centered around expanding the phenotypic spectrum of variants and documenting the management of this disease to bolster knowledge and promote evidence-based practice.
Submission Deadline 28/02/2025
Other specific requirements None
Contact person  André Travessa
Institution  Department of medical genetics, Centro Hospitalar Universitário Lisboa Norte (CHULN), Lisbon
Contact

DeFiD: DEnosumab for the treatment of Fibrous Dysplasia/McCune-Albright Syndrome in adults

Title DeFiD: DEnosumab for the treatment of Fibrous Dysplasia/McCune-Albright Syndrome in adults
Target Fibrous Dysplasia/McCune-Albright Syndrome ((FD/MAS; OMIM#174800, ORPHA:249 )
Summary FD/MAS is a rare disease with high risk for pain, fractures, decreased quality of life and currently there is no cure. Study objective is to investigate whether 3 monthly Denosumab will improve the clinical, radiological and biochemical manifestations of Fibrous dysplasia bone lesions in a double-blind placebo 6 months intervention study followed by a 6 months open-label study. Patients over 18 years old with an established diagnosis of FD/MAS and persistent pain at the site of lesions with a maximum pain score of ≥4/10 as measured by the Visual Analogue Scale (VAS) will be randomized to treatment with either subcutaneous Denosumab 120mg or placebo at baseline and 3 months in a blinded fashion. At 6 months, after 2 injections, patients with pain score <4 will exit the study to discontinue study medication and proceed in usual care, while patients with pain score ≥4 or lesional growth will be offered Denosumab 120 mg at 6 and 9 months in an open-label design.
Submission Deadline 04/12/2024
Other specific requirements  None
Contact person  Natasha Appelman-Dijkstra
Institution Leiden University Medical Center, Department of Internal Medicine, Endocrinology, Leiden, The Netherlands
Contact

GNPNAT1-related skeletal dysplasia: expanding phenotype and genotype

Title  GNPNAT1-related skeletal dysplasia: expanding phenotype and genotype
Target GNPNAT1 / Rhizomelic dysplasia, Ain-Naz type (MIM 616510 )
Summary Multicentric collaboration to gather clinical and molecular data on case series of patients with identified variantes in GNPNAT1 gene. This prohject will aim to expand the clinical and molecular espectrum of this recently described group of conditions, perform funcional and metabolic studies that help clarify the physiopathology and clarifiy pathogenicity of variants.
Submission deadline 01/09/2024
Other specific requirements  Possible fibroblasts for functional and metabolic studies
Contact person  Karen Heath; Valérie Cormier-Daire; Sérgio B. Sousa
Institution INGEMM – Hospital Universitario La Paz, Madrid; Hôpital Necker-Enfants Malades, Paris; Hospital Pediátrico de Coimbra
Contact