Progressive Pseudorheumatoid Dysplasia Research Articles

Progressive Pseudo-Rheumatoid Dysplasia a Rare Genetic Musculoskeletal Condition Causing Crippling Disability in a Young Boy- a Case Report

Progressive pseudo-rheumatoid dysplasia (PPRD) is an uncommon genetic condition inherited in an autosomal recessive mode caused by a mutation in the WNT1-inducible signaling pathway protein 3 (WISP3) located on chromosome 6q21. In this condition, the articular cartilage gradually deteriorates, causing severe discomfort, stiffness, and joint deformities with a relatively high prevalence in Middle Eastern countries. Camptodactyly and platyspondyly are the standard features found in this condition. We present a very young boy diagnosed with bilateral hip dysplasia during early childhood and developing increasing pain, stiffness and deformities in the hands, elbow, hips, knee, and ankle. The diagnosis was suspected based on characteristic clinical and radiological features. The diagnosis was confirmed by genetic testing and the absence of elevated serum inflammatory markers. He was born out of a consanguineous marriage, and his parents were unaffected. They are three siblings; his elder sister has a milder condition, while his elder brother is unaffected. There were no adverse events during pregnancy. Birth weight was within normal limits, met all developmental milestones on time, and had no significant past medical history. Compounded by hip dysplasia, he developed a severe disability and had to undergo joint replacement surgery at a very young age. PPRD should be suspected in children from Middle Eastern countries of 3-8 years of age who present with multiple joint pain and stiffness and are born out of inbred family marriages. Diagnosis can be suspected by the characteristic clinical and radiological features coupled with the absence of raised serum inflammatory markers and confirmed by genetic testing. Genetic counseling and pre-marriage testing are of valuable help in prevention.

Clinical and molecular characterization in a cohort of patients with progressive pseudorheumatoid dysplasia.

Progressive pseudorheumatoid dysplasia (PPRD), a rare autosomal recessive syndrome, is a type of skeletal dysplasia associated with pain, stiffness, swelling of multiple joints, and the absence of destructive changes. PPRD occurs due to loss of function pathogenic variants in WISP3 (CCN6) gene, located on chromosome 6q22. In this study, 23 unrelated Egyptian PPRD patients were clinically diagnosed based on medical history, physical and radiological examinations, and laboratory investigations. Sequencing of the whole WISP3 (CCN6) exons and introns boundaries was carried out for all patients. A total of 11 different sequence variations were identified in the WISP3 (CCN6) gene, five of them were new pathogenic variants: the NM_003880.3: c.80T>A (p.L27*), c.161delG (p.C54fs*12), c.737T>C (p.Leu246Pro), c.347-1G>A (IVS3-1G>A), and c.376C>T (p.Q126*). The results of this study expand the spectrum of WISP3 (CCN6) pathogenic variants associated with PPRD. Clinical and genetic analysis is important for proper genetic counseling to curb this rare disorder in the families.

SPONDİLOEPİ (META) FİZYAL DİSPLAZİ ÖN TANILI BEŞ TÜRK ERKEK HASTADAKİ GENETİK ETYOLOJİNİN ARAŞTIRILMASI

OBJECTIVE: Skeletal dysplasias is a complex disease group characterized by disproportionate short stature and various orthopedic complications. X-Linked Spondyloepiphyseal Dysplasia Tarda is an X-linked inherited skeletal dysplasia accompanied by progressive spondyloepi(meta)physeal dysplasia and premature osteoartritis. The gene related to the disorder is trafficking protein particle complex 2 (TRAPPC2). Progressive pseudorheumatoid dysplasia (PPRD) is characterized by enlargement of the elbow joints and arthritis-like findings. It is an autosomal recessive subtype of skeletal dysplasia caused by mutations in cellular communication network factor 6 (CCN6) gene located on chrosomal region 6q21. In this study, it was aimed to diagnose five male individuals with an X-linked or autosomal recessive inheritance pattern, who have not been diagnosed for years, to identify possible treatments and to offer prenatal pmreimplantation genetic testing. MATERIAL AND METHODS: Five male siblings with skeletal dysplasia with an uncertain inheritance either X-linked or autosomal recessive pattern were included in this study, Whole Exome Sequencing (WES) was applied to the four affected cases. Sanger Sequencing was performed in one affected case and four healthy individuals. RESULTS: Homozygous c.210C>A (p.Cys70Ter) and homozygous c.302G>A (p.Gly101Glu) mutations in the CCN6 gene were found in all affected siblings. Thus, the final diagnosis after WES was autosomal recessive PPRD despite the possibility of an X-linked recessive pattern. CONCLUSIONS: This study presents a series of the oldest patients diagnosed with Progressive pseudorheumatoid dysplasia, normally a childhood disease, with an average age of 54.6. The p.Cys70Ter alteration is the most frequent pathogenic variant in Turkish patients. This study is also important in terms of showing that Progressive pseudorheumatoid dysplasia has no significant effect on life expectancy. At the same time, this study shows the progression of this disease and clinical findings that may accompany lifetime.

CCN6 influences transcription and controls mitochondrial mass and muscle organization.

Mutations in Cellular Communication Network Factor 6 (CCN6) are linked to the debilitating musculoskeletal disease Progressive Pseudo Rheumatoid Dysplasia (PPRD), which disrupts mobility. Yet, much remains unknown about CCN6 function at the molecular level. In this study, we revealed a new function of CCN6 in transcriptional regulation. We demonstrated that CCN6 localizes to chromatin and associates with RNA Polymerase II in human chondrocyte lines. Using zebrafish as a model organism we validated the nuclear presence of CCN6 and its association with RNA Polymerase II in different developmental stages from 10 hpf embryo to adult fish muscle. In concurrence with these findings, we confirmed the requirement of CCN6 in the transcription of several genes encoding mitochondrial electron transport complex proteins in the zebrafish, both in the embryonic stages and in the adult muscle. Reduction in the expression of these genes upon morpholino-mediated knockdown of CCN6 protein expression led to reduced mitochondrial mass, which correlated with defective myotome organization during zebrafish muscle development. Overall, this study suggests that the developmental musculoskeletal abnormalities linked with PPRD could be contributed at least partly by impaired expression of genes encoding mitochondrial electron transport complexes due to defects in CCN6 associated transcriptional regulation.

A novel WISP3 mutation in a Chinese patient with progressive pseudorheumatoid dysplasia.

Progressive pseudorheumatoid (PPD) arthritis is a rare genetic disorder resulting from mutations in the Wnt-1 inducible signaling pathway protein-3 gene (WISP3 gene). The disease is characterized by non-inflammatory polyarthropathy, degeneration of joints, metaphyseal dysplasia of limbs and platyspondyly. Here, we report a Chinese PPD patient with a novel WISP3 mutation. A 24-year-old female was presented with 17-year history of polyarticular deformity. At the age of 9, she had decreased mobility in her wrists, elbows, ankles, and knees. After a series of tests including the next generation sequencing gene panel for the WISP3 gene were performed, the patient was finally diagnosed with progressive pseudorheumatoid dysplasia. This patient had a compound mutation in the exon. The c.868_869delAG has been reported as a rare mutation in Caucasian PPD and identified for the first time in Chinese patient. Thus, our study helps to further expand the WISP3 mutation spectrum in PPD patients. Further, our case provides a thorough description of clinical symptoms and the imaging characteristics. This case is also the first to describe the delineation of cartilage destruction and an absence of an inflammatory process of PPD on musculoskeletal ultrasound. The disease of PPD is easily misdiagnosed as rheumatoid arthritis, ankylosing spondylitis. Early detection of this entity, followed by confirmation via imaging and a genetic test, can save patients from unnecessary investigations and toxic medications.

Unique mutation spectrum of progressive pseudorheumatoid dysplasia in the Chinese population: a retrospective genotype–phenotype analysis of 105 patients

BackgroundProgressive pseudorheumatoid dysplasia (PPRD) is a rare genetic disease with autosomal recessive inheritance. There was a lack of genotype–phenotype correlation data from the Chinese population. This study aimed to identify the genotype and phenotype characteristics of Chinese PPRD patients and to conduct a genotype–phenotype analysis of Chinese PPRD patients.MethodsGenetic analysis was performed for suspected PPRD patients from Peking Union Medical College Hospital. Medical records were collected from the electronic medical record system and patient-held portable health records. Published Chinese PPRD cases were gathered from both international and Chinese local databases. We collected demographic information, genetic variants, clinical manifestations, and imaging characteristics for further analysis.ResultsWe included 105 Chinese PPRD patients in the current study. Thirty-three variants, including nine novels and five hotspot variants, were identified, with 26/33 (79%) variants exclusively seen in the Chinese population. Chinese PPRD patients share a phenotype similar to that in international reports. Joint involvement may progress with age (R2 = 0.2541). Long bone shortening and severe deformities occur in three patients with biallelic null variants, of which at least one variant is located in exon 2. Among hotspot variants, c.624dupA (p.C209Mfs*21) were associated with later onset and more involved joints. Elbow joints were more likely to be affected in patients carrying c.624dupA (p.C209Mfs*21) and c.866dupA (p.S209Efs*13). Shoulder joints are more likely to be involved in patients with biallelic null variants (P = 0.027).ConclusionsChinese PPRD patients share a unique mutation spectrum. Among the five hotspot variants, c.624dupA is associated with later onset of disease, more extensive joint involvement, and a tendency to affect elbow joints. Biallelic null variants with at least one variant in exon 2 could be a likely cause of long bone shortening and severe deformities.

Progressive pseudorheumatoid dysplasia in an Omani family: a case report

Background: Progressive pseudorheumatoid dysplasia (PPRD) is an inherited autosomal recessive musculoskeletal condition caused by mutations in the Cellular Communication Network Factor 6 (CCN6) gene. This causes a variety of clinical features such as short stature, genu varum, etc. Case Presentation: This study reported cases of three patients from the same family who exhibited the clinical features of PPRD, and the condition was diagnosed through confirmatory genetic testing. The whole exome sequencing test results for the 15-year-old and 3-year-old males revealed a class-5 pathogenic homozygous mutation in the CCN6 gene, resulting in both individuals being diagnosed with autosomal recessive PPRD. The results for the third patient had not come out yet. Conclusion: For patients with PPRD, it is necessary to take the full family history and genetic testing that might help in the diagnosis and treatment of the condition.

Bijadushti Janya Asthi Dhatu Kshaya with Special Reference to Progressive Pseudo-Rheumatoid Arthropathy (Dysplasia) of Childhood – A Case Report

Progressive pseudo-rheumatoid arthropathy dysplasia of childhood PPAC PPD is a genetic disorder characterized by poly articular non-inflammatory arthropathy due to impaired articular cartilage formation and maintenance caused by mutation in WISP3 WNT1-inducible signalling pathway protein 3 gene. Osteoarthritis joint space reduction and contracture formation results in severe handicap and incapacitation. Although few preventive measures are described to avert genetic disorders Ayurveda generally considers genetic disorders incurable. Hence palliative care becomes very important in managing such conditionsA North Indian 11.5 years old male child with Bijadushti Janya Vyadhi genetic disorder diagnosed as Progressive pseudo-rheumatoid arthropathy dysplasia of childhood PPAC PPD approached for pain and swelling of multiple joints gait and postural problems. Bijadushti was responsible for Asthi Dhatu Kshyaya diminution of bone tissue Sandhi Shotha joint swelling Sandhi Sankoch contractures Karma Hani loss of action and complications like lameness kyphosis and short stature in this case.He was managed with Ayurvedic treatment and Yoga and showed encouraging improvements in a short period. The treatment plan included Deepana-Pachana improving the digestion and metabolism Abhyanga therapeutic massage Swedana sudation and Basti therapeutic enema along with Asthidhatu Vardhana Chikitsa measures to supplement bone tissue Rasayana rejuvenation and range of motion ROM exercises in the form of Sukshma Vyayama gentle joint movements synchronized with breathing. If the etiopathogenesis of incurable genetic disorders is understood in the light of Ayurvedic tenets and palliative treatment is planned accordingly the patientrsquos life can be improved by providing symptomatic relief.

A rare case of progressive pseudorheumatoid dysplasia

Progressive pseudorheumatoid dysplasia is a rare, autosomal recessive, noninflammatory musculoskeletal disorder caused by mutations occurring in the WNT1- protein present in 3 gene. Usual presentation is arthralgia, joint stiffness, contractures with primary involvement in joint cartilage. We present a 13-year-old female child presented with history of short stature, bowing of legs and curving of spine and inability to walk normally since the past two years. The symptoms have been progressively worsening for the past one year. Progressive pseudo rheumatoid dysplasia is a rare form of spondyloepimetaphyseal dysplasia and is clinically misdiagnosed as juvenile idiopathic arthritis. Any patient presenting with musculoskeletal symptoms should be evaluated appropriately to start appropriate therapy in time.

HLA-DRB typing among polyarticular juvenile idiopathic arthritis and progressive pseudorheumatoid dysplasia patients

Juvenile Idiopathic Arthritis (JIA) is a multi-factorial disease influenced both by environmental and genetic factors. Progressive pseudorheumatoid dysplasia (PPD) is a rare autosomal recessive genetic disorder affecting multiple joints, mimicking JIA. Aim of the work: to reveal the frequency of HLA-DR types among the studied patients and to correlate the different allele variations clinically. Patients and methods: Thirty JIA patients, in addition to 15 molecularly diagnosed PPD patients were subjected to full history taking and clinical examination. HLA-DRB1 typing was performed to 24/30 JIA and 12/15 PPD cases and thirty healthy age and sex matched children who were included as a control group. Results: The JIA patients were 22 females and 8 males with mean age of 15.8 ± 1.96 years and disease duration 5.3 ± 4.4 years. PPD patients were 8 males and 7 females with mean age of 8.7 ± 3.06 years and disease duration 3.95 ± 2.68 years. A significant frequency of HLA-DRB 04 (p = 0.049) among JIA patients was present in comparison to the controls (OR = 2.81, CI:1.02–7.75), other risky alleles were HLA-DRB 10, 13 and 15. However, HLA-DRB 01, 03, 07, 11 and 14 were found to be protective. HLA-DRB 01, 04, 10 and 13 were found to be risky alleles in PPD. However, HLA 03, 07, 11 and 15 were found to be protective alleles among PPD patients. Conclusion: HLA-DRB 04 was found in a higher frequency in JIA patients with a significant difference in comparison to the controls, denoting that it may play a role in the genetic pathogenesis of JIA.

Mesenchymal stromal cells from a progressive pseudorheumatoid dysplasia patient show altered osteogenic differentiation

BackgroundProgressive pseudorheumatoid dysplasia (PPRD) is a rare autosomal recessive non-inflammatory skeletal disease with childhood onset and is characterized by a progressive chondropathy in multiple joints, and skeletal abnormalities. To date, the etiopathological relationship between biological modification occurring in PPRD and genetic mutation remains an open issue, partially due to the limited availability of biological samples obtained from PPRD patients for experimental studies.Case presentationWe describe the clinical features of a PPRD patient and experimental results obtained from the biological characterization of PPRD mesenchymal stromal cells (MSCs) and osteoblasts (OBs) compared to normal cell populations. Phenotypic profile modifications were found in PPRD compared to normal subjects, essentially ascribed to decreased expression of CD146, osteocalcin (OC) and bone sialoprotein in PPRD MSCs and enhanced CD146, OC and collagen type I expression in PPRD OBs. Gene expression of Dickkopf-1, a master inhibitor of WNT signaling, was remarkably increased in PPRD MSCs compared to normal expression range, whereas PPRD OBs essentially exhibited higher OC gene expression levels. PPRD MSCs failed to efficiently differentiate into mature OBs, so showing a greatly impaired osteogenic potential.ConclusionsSince all regenerative processes require stem cell reservoirs, compromised functionality of MSCs may lead to an imbalance in bone homeostasis, suggesting a potential role of MSCs in the pathological mechanisms of PPRD caused by WNT1-inducible signaling pathway protein-3 (WISP3) mutations. In consideration of the lack of compounds with proven efficacy in such a rare disease, these data might contribute to better identify new specific and effective therapeutic approaches.

The genetics of progressive pseudorheumatoid dysplasia.

The genetics of progressive pseudorheumatoid dysplasia.

A novel compound heterozygous mutation of WISP3 in progressive pseudorheumatoid dysplasia mimicking juvenile idiopathic arthritis.

A novel compound heterozygous mutation of WISP3 in progressive pseudorheumatoid dysplasia mimicking juvenile idiopathic arthritis.

Progressive pseudo-rheumatoid dysplasia -a rare genetic disorder: Case Report

Progressive pseudorheumatoid dysplasia (PPRD), also known as spondyloepiphyseal dysplasia tarda with progressive arthropathy (SEDT-PA), is an autosomal recessive disorder, resulting from mutations in the WNT1-inducible signaling pathway protein 3 (WISP3) gene involving the axial skeleton as well as small peripheral joints. Because of rarity here we present a case of 14-year-old boy, 1st issue of consanguineous parents who was presented with pain & gradual development of contracture in 3rd distal interphalangeal joint of right hand when he was 4-year-old, then gradual involvement of other interphalangeal joints of hands, bilateral wrists, elbows, shoulder, knees &ankles occurred over years with the development of contractures and restricted movement. For last few years, he developed difficulty in walking. Clinically spinal scoliosis and coxa vara was present. Mobility of spines and multiple joints including proximal & distal interphalangeal joints of hands, wrists, elbows, shoulders, knees, ankles were restricted with flexion contractures. The gait of the patient was limping. Radiological evaluation showed osteopenia in X-ray of pelvis with both hip joints and both knee joints. Generalized osteopenia, fusiform swelling in distal interphalangeal joint, flexion deformity in distal interphalangeal joint of middle and ring fingers of both hand was shown in X-ray of both hands. MRI of lumbosacral spine showed dorso-lumbar vertebral bodies dysplastic with anterior wedging producing bullet nose. Superior epiphyseal deformity was also noted in lower dorsal bodies suggestive of spondyloepiphyseal dysplasia of dorso-lumbar spine. Genetic study showed homozygous nonsense variation in exon 5 of the WISP3 gene suggestive pathogenic variant. Finally, he was diagnosed as a case of PPRD and treated with physiotherapy, family counseling, and anti-inflammatory medications.
 AKMMC J 2022; 13(1) : 52-55

Specific early signs and long-term follow-up findings of progressive pseudorheumatoid dysplasia (PPRD) in the Turkish cohort.

Progressive pseudorheumatoid dysplasia (PPRD) is a spondyloepiphyseal dysplasia caused by biallelic variants in CCN6. This study aimed to describe the early signs and follow-up findings in 44 Turkish PPRD patients. The patients with progressive stiffness of multiple joints, characteristic wide metaphysis of interphalangeal (IP) joints and platyspondyly were clinically diagnosed with PPRD. Fifteen patients who had first symptoms under 3 years of age were grouped as early-onset, while others were grouped as classical. CCN6 sequencing was performed in 43 patients. Thirteen pathogenic/likely pathogenic variants were identified, five were novel. c.156C>A(p.Cys52*) variant was found in 53.3% of the families. The initial symptom in the early-onset group was genu varum deformity, while it was widening of IP joints in the classical group. The median age of onset of symptoms and of diagnosis was 4 and 9.7 years, respectively. The mean follow-up duration was 5.6 years. The median age of onset of IP, elbow, knee and hip stiffness, which became progressive with growth was 5, 9, 9 and 12.2 years, respectively. Waddling gait occurred in 97.7% of the patients. A total of 47.7% lost independent walking ability at the median age of 12 years. In the early-onset group, waddling gait occurred earlier than in classical group (P < 0.001). Two patients had atypical presentation with late-onset and mild or lack of IP involvement. We observed that genu varum deformity before the age of 3 years was an early sign for PPRD and almost half of the patients lost walking ability at the median age of 12 years.

Progressive pseudorheumatoid dysplasia misdiagnosed as juvenile idiopathic arthritis: a case report

BackgroundProgressive pseudorheumatoid dysplasia is a rare, autosomal recessively inherited, noninflammatory musculoskeletal disorder caused by mutations occurring in the WNT1-inducible signaling pathway protein 3 gene. Joint cartilage is the primary site of involvement, leading to arthralgia, joint stiffness, contractures, enlargement of the epiphyses and metaphysis of the hand joints, spinal abnormalities, short stature, early osteoarthritis, and osteoporosis. Juvenile idiopathic arthritis is the most common chronic rheumatic disease in childhood and has unknown etiology. Clinical features of progressive pseudorheumatoid dysplasia resemble those of juvenile idiopathic arthritis. Patients with progressive pseudorheumatoid dysplasia are usually misdiagnosed as having juvenile idiopathic arthritis.Case presentationA 13-year-old Yemeni female presented to the rheumatology clinic with a history of joint pains, bone pains, and bone deformity for 7 years. Weight and height were below the third percentiles. There was no tender swelling of metacarpophalangeal and interphalangeal joints, and she presented with scoliosis. Radiographs of the hands revealed the widening of the epiphyses. Progressive pseudorheumatoid dysplasia was suspected, and genetic testing for WNT1-inducible signaling pathway protein 1, 2, and 3 was requested with these findings. A homozygous, likely pathogenic variant was identified in the WNT1-inducible signaling pathway protein 3 gene, which confirmed our diagnosis.ConclusionProgressive pseudorheumatoid dysplasia is a rare form of spondyloepimetaphyseal dysplasia and is clinically misdiagnosed as juvenile idiopathic arthritis. It is crucial to consider progressive pseudorheumatoid dysplasia, especially in patients with standard inflammatory markers who are being followed up for juvenile idiopathic arthritis and not improving with antirheumatic intervention.

Progressive Pseudorheumatoid Dysplasia of Childhood (PPRD)-A Case Series with Recurrent c.740_741del Variant.

Progressive pseudorheumatoid dysplasia (PPRD) is an autosomal recessive arthropathy, affecting school-aged children. It is characterized by progressive degeneration of the articular cartilage. The majority of the pathogenic variations are found in exon 2, exon 4, and exon 5 of the putative gene, CCN6 (WISP3). Three unrelated individuals with clinical diagnosis of PPD were included in this study. Detailed clinicoradiological evaluation was attempted with brief literature review. Exome sequencing was performed in all three cases. All the pathogenic variations detected in our cohort were located in exons 2 and 4 of WISP3 gene. Though the clinicoradiological features are already well described, this study in north India highlights the occurrence of a recurring pathogenic variant. The c.740_741del variant was a recurrent pathogenic variant seen in all three patients in this cohort. This may be a common pathogenic variant in the North Indian population; however, a larger cohort needs to be studied before drawing final conclusions. A proper molecular diagnosis is a must to end the diagnostic odyssey, safeguarding patients with PPRD from unnecessary use of drugs like corticosteroids.

A retrospective study of nine patients with progressive pseudorheumatoid dysplasia: to explore early diagnosis and further treatment.

Most patients with progressive pseudorheumatoid dysplasia (PPRD) are initially misdiagnosed because of disease rarity and lack of awareness by most clinicians. The purpose of this study was to provide further early diagnostic options and potential treatment to patients with PPRD. A retrospective study was performed by collecting and organizing clinical manifestations, radiographic features, laboratory test results, genetic test outcome, treatment, and follow-up records of the patients with PPRD. Age of diagnosis and genotype-phenotype correlation were further analyzed. Nine PPRD children with causative CCN6 mutation were included. There were 3 pairs of siblings and 1 patient from inbred family. Five patients were primarily misdiagnosed as juvenile idiopathic arthritis (JIA). The interval between onset of symptoms and definite diagnosis of 8 patients varied from 3.6 to 20years. Symptoms at the onset included enlarged and stiff interphalangeal joints of the fingers, gait disturbance, or joint pain. Laboratory tests revealed normal range of inflammatory parameters. Radiographic findings disclosed different degrees of abnormal vertebral bodies and epiphyseal enlargement of the interphalangeal joints. After the treatment of calcitriol in 5 patients with low level 25-hydroxyvitamin D3 for around 1.25years to 1.75years, 2 patients kept stable, while 3 of them improved gradually. Combining the patient's family history, clinical features, normal inflammatory markers, and the characteristic radiographic findings, the clinical diagnosis of PPRD for the patients could be obtained at very early stage of the disease. The patients with PPRD carrying c.624dupA variant in CCN6 may have delayed onset. Underlying vitamin D deficiency should be sought and corrected in patients with PPRD.

Late Diagnosis of Progressive Pseudorheumatoid Dysplasia in an Adolescent Patient: A Case Report and Review of the Literature

Late Diagnosis of Progressive Pseudorheumatoid Dysplasia in an Adolescent Patient: A Case Report and Review of the Literature

Genetic disorders with symptoms mimicking rheumatologic diseases: A single-center retrospective study

Musculoskeletal symptoms may be due to noninflammatory causes, including genetic disorders. We aimed to examine the final genetic diagnosis in patients who presented with musculoskeletal complaints to the rheumatology department. Patients who presented to the Department of Pediatric Rheumatology and were referred to the pediatric genetic department between January 2015 and May 2019 were evaluated retrospectively. A total of 60 patients, 19 boys (31.66%), with a mean age of 12.46 ± 1.41 years were included in the study. The total consanguinity rate was 25%. The most common (29.5%) cause of referral to the pediatric genetic department was the presence of skeletal anomalies (such as camptodactyly, clinodactyly, and short stature) with accompanying joint findings. Approximately one-third of the patients (n: 19) were diagnosed and followed up by the pediatric genetics department. The diagnoses of patients were as follows: camptodactyly, arthropathy, coxa vara, and pericarditis (CACP) syndrome (n: 3); trichorhinophalangeal syndrome (n: 1); progressive pseudorheumatoid dysplasia (n: 2); LIG4 syndrome (n: 1); H syndrome (n: 1); spondyloenchondrodysplasia (SPENCD) (n: 3); and nonspecific connective tissue disorders (n: 8). In the differential diagnosis of patients who are referred to the Department of Pediatric Rheumatology with complaints of the musculoskeletal system, genetic disorders should also be considered.