CACP: Study on Camptodactyly - Arthropathy - Coxa Vara - Pericarditis (CACP) Syndrome

NCT07468461 | Recruiting

• 1 other identifier: CACP
• Study Type: observational
• Target: 15
• Locations: 3 countries
• Sites: 10

Brief Summary

CACP syndrome is a rare autosomal recessive disorder characterized by the triad of camptodactyly, non-inflammatory arthropathy with synovial hyperplasia, and coxa vara. Occasionally, non-inflammatory pericarditis and pleural effusion may also occur. This syndrome is likely underdiagnosed due to its rarity. Epidemiological information is limited to isolated case reports or small patient series, with the largest reported cohort including 35 patients. The genetic cause of CACP syndrome is associated with mutations in the PRG4 gene, located on chromosome 1q31.1. While clinical signs (camptodactyly, non-inflammatory arthropathy, and coxa vara) and radiological findings suggest the diagnosis, genetic testing confirms it by identifying pathogenic biallelic mutations in PRG4. To date, twenty-two mutations have been identified, all leading to premature stop codons and the absence of functional lubricin. However, the exact pathophysiology of CACP syndrome remains incompletely understood. Clinical manifestations of CACP syndrome can vary, even within the same family. The progressive and slow onset can initially present as an incomplete clinical picture. However, camptodactyly (85- 100%) and arthropathy (100%) are constant features. Although genetically homogeneous, CACP exhibits significant intra- and interfamilial phenotypic variability due to secondary genetic factors, environmental modifiers, and complex molecular mechanisms. Camptodactyly is symmetrical, with variable distribution. It may affect fingers or toes and can be congenital or develop during childhood. Arthropathy is symmetrical, primarily involving large joints (wrists, knees, ankles, elbows, and hips). Coxa vara is present in 50-90% of cases, is progressive, and tends to worsen with age. Spinal abnormalities such as lordosis, scoliosis, and kyphosis are possible, though the cervical spine is generally spared. The articular manifestations of CACP syndrome may mimic juvenile idiopathic arthritis (JIA), and patients are often initially misdiagnosed and treated inappropriately. Joints appear swollen due to non-inflammatory synovial effusion and synovial thickening. They develop contractures, functional limitations, and sometimes musculoskeletal pain. Non-inflammatory pericarditis is reported in 30% of published cases, with variable clinical courses that may require surgical intervention in cases of constrictive pericarditis. The routine pathway of assessments and follow-up for patients with CACP syndrome includes an initial detailed evaluation and regular monitoring. Following the diagnosis, which is based on clinical history, imaging studies, and genetic confirmation of PRG4 mutations, patients undergo periodic clinical visits, generally scheduled every six months. During these visits, the progression of the disease, articular symptoms (e.g., camptodactyly, mobility limitations), and possible extraarticular complications, such as pericarditis, are assessed. Radiological (e.g., X-rays, MRI) and laboratory assessments, however, can be spaced out over longer intervals compared to the schedule of clinical visits, typically every 1-2 years, unless specific indications arise. Nonetheless, these examinations may be requested based on contingent clinical needs, such as a sudden worsening of symptoms or suspicion of complications. This flexible approach helps to balance thorough disease monitoring with minimizing the burden on patients, while ensuring personalized and timely management of the condition. At present, there is no specific pharmacological treatment for CACP. Management is primarily symptomatic and aimed at preventing joint deformities and extra-articular complications. Currently, no experimental therapies are available for CACP syndrome, but future research could explore gene therapy, regenerative medicine, and biologics. This study, involving pediatric and pediatric rheumatology centers across Italy and Europe, aims to collect epidemiological, clinical, and therapeutic data from a large cohort of patients. Its goals include better defining the disease's characteristics, understanding its natural history, and evaluating different therapeutic approaches and their efficacy. The study will also analyze potential genotypephenotype correlations.

Conditions

Camptodactyly; Arthropathy; Coxa Vara; Pericarditis

Keywords

Camptodactyly - Arthropathy - Coxa Vara - Pericarditis (CACP) Syndrome

Outcome Measures

Primary Outcomes (9)

• Incidence of CACP Syndrome

  Number of newly diagnosed cases of CACP syndrome identified during the study period, reported per population at risk.

  From enrollment to the next 10 years

• Geographic and Ethnic Distribution of CACP Cases

  Number and proportion of confirmed CACP cases per participating country and center and stratified by self-reported ethnicity.

  From the enrollment to the next 10 years

• Clinical Characteristics

  * Frequency of Individual Clinical Manifestations: Proportion of patients presenting with each predefined clinical feature (camptodactyly, non-inflammatory arthropathy, coxa vara, non-inflammatory pericarditis), reported individually as present/absent. * Interindividual Clinical Variability: Exploration of variations in symptom presentation and disease progression among individuals.

  From enrollment to the next 10 years

• Disease progression

  Assessment of the clinical and radiological course of CACP syndrome, including measurement of disease severity and progression rate.

  From enrollment to the next 10 years

• Disease Complications

  * Incidence of Complications: Proportion of patients developing predefined complications (e.g., constrictive pericarditis, pleural effusion), each reported separately. * Management of Complications: Type and frequency of therapeutic interventions used for the management of CACP-related complications.

  From enrollment to the next 10 years

• Distribution of PRG4 Gene Variants

  * Number and proportion of participants carrying each identified pathogenic or likely pathogenic variant in the PRG4 gene. * Classification of participants into subgroups based on specific PRG4 variants, with descriptive comparison of associated clinical characteristics.

  from the enrollment to the next 10 years

• Genotype-Phenotype Association

  Statistical association between specific PRG4 variants and predefined clinical manifestations or severity disease.

  From enrollment to the next 10 years

• Geographic and Ethic Distribution of PRG4 Variants

  Number and proportion of specific PRG4 variants stratified by country and center and ethnicity.

  From enrollment to the next 10 years

• Post-Diagnosis Treatments

  After a definitive diagnosis, treatments focus on symptom management and improving patients' quality of life. Commonly used medications include: * Non-steroidal anti-inflammatory drugs (NSAIDs) * Corticosteroids * Intra-articular hyaluronic acid (HA) injections

  from the enrollment to the next 10 years

Secondary Outcomes (7)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  from the enrollment to the next 10 years

• Change from baseline in functional disability assessed by Childhood Health Assessment Questionnaire (CHAQ) score

  from the enrollment to the next 10 years

• Change from baseline in musculoskeletal pain intensity assessed by Visual Analogue Scale (VAS)

  from enrollement to the next 10 years

• Change from baseline in patient global well-being assessed by Patient Global Assessment (PGA) scale

  from enrollement to the next 10 years

• Time from symptom onset to confirmed diagnosis of CACP syndrome

  from the enrollment to the next 10 years

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Study population will be selected at the participating centers according to inclusion criteria.

You may qualify if:

• Patients with clinical diagnosis and genetic confirmation of CACP syndrome.
• Patients diagnosed during pediatric age (\<18 years).
• Time frame: Patients diagnosed with CACP between January 2005 and January 1, 2026.
• Informed consent obtained from parents or legal guardians.

You may not qualify if:

• Patients without genetic confirmation of the diagnosis.
• Lack of informed consent from parents or legal guardians.
• Patients diagnosed before January 1, 2005, or after January 1, 2026.

Sponsors & Collaborators

• Meyer Children's Hospital IRCCS: lead

Study Sites (10)

Ospedale Pediatrico Giovanni XXIII

Bari, Italy

NOT YET RECRUITING

Rheumatology Unit, Meyer Children's Hospital

Florence, Italy

RECRUITING

IRCCS Istituto Giannina Gaslini,

Genova, Italy

RECRUITING

ASST Fatebenefratelli

Milan, Italy

NOT YET RECRUITING

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Italy

RECRUITING

Azienda Ospedaliera di Padova

Padua, Italy

NOT YET RECRUITING

Santa Maria Goretti Hospital

Roma, Italy

NOT YET RECRUITING

Centro di Reumatologia Pediatrica

Udine, Italy

NOT YET RECRUITING

Hiospedal Sant Joan de Déu

Barcelona, 208950, Spain

NOT YET RECRUITING

Ankara Pediatrik Romatoloji Bilim Dalý Hacettepe Üniversitesi

Ankara, 06105, Turkey (Türkiye)

NOT YET RECRUITING

Related Publications (6)

• Al-Mayouf SM, Almutairi N, Alismail K. The Efficacy of Yttrium-90 Radiosynovectomy in Patients with Camptodactyly-Arthropathy-Coxa Vara-Pericarditis Syndrome. Mol Imaging Radionucl Ther. 2017 Feb 5;26(1):33-37. doi: 10.4274/mirt.29484.

  PMID: 28291008 BACKGROUND

• Albuhairan I, Al-Mayouf SM. Camptodactyly-arthropathy-coxavara-pericarditis syndrome in Saudi Arabia: clinical and molecular genetic findings in 22 patients. Semin Arthritis Rheum. 2013 Oct;43(2):292-6. doi: 10.1016/j.semarthrit.2012.11.004. Epub 2013 Jan 2.

  PMID: 23290693 BACKGROUND

• Singh S, Badiger VA, Balan S, Nampoothiri S, Rao AP, Shah H, Bhavani GS, Narayanan DL, Girisha KM. Thirteen Indians with camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Clin Dysmorphol. 2024 Oct 1;33(4):152-159. doi: 10.1097/MCD.0000000000000500. Epub 2024 Mar 22.

  PMID: 38856641 BACKGROUND

• Ciullini Mannurita S, Vignoli M, Bianchi L, Kondi A, Gerloni V, Breda L, Ten Cate R, Alessio M, Ravelli A, Falcini F, Gambineri E. CACP syndrome: identification of five novel mutations and of the first case of UPD in the largest European cohort. Eur J Hum Genet. 2014 Feb;22(2):197-201. doi: 10.1038/ejhg.2013.123. Epub 2013 Jun 12.

  PMID: 23756439 BACKGROUND

• Sathiyaseelan SL, Krishna K, Agarwal D, Oswal JS. Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome. BMJ Case Rep. 2024 Jul 1;17(7):e260146. doi: 10.1136/bcr-2024-260146.

  PMID: 38955384 BACKGROUND

• Yilmaz S, Uludag Alkaya D, Kasapcopur O, Barut K, Akdemir ES, Celen C, Youngblood MW, Yasuno K, Bilguvar K, Gunel M, Tuysuz B. Genotype-phenotype investigation of 35 patients from 11 unrelated families with camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome. Mol Genet Genomic Med. 2018 Mar;6(2):230-248. doi: 10.1002/mgg3.364. Epub 2018 Feb 4.

  PMID: 29397575 BACKGROUND

MeSH Terms

Conditions

Joint Diseases; Coxa Vara; Pericarditis; Syndrome

Condition Hierarchy (Ancestors)

Musculoskeletal Diseases; Bone Anteversion; Bone Malalignment; Bone Diseases; Torsion Abnormality; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Heart Diseases; Cardiovascular Diseases; Disease; Pathologic Processes

Central Study Contacts

Teresa Giani, MD, PhD

CONTACT

+39 0555662924; teresa.giani@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 17, 2026
• First Posted: March 12, 2026
• Study Start: August 1, 2025
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2038
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

TU (1); IT (8); ES (1)