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Progressive pseudorheumatoid dysplasia(PPRD)

MedGen UID:
96581
Concept ID:
C0432215
Congenital Abnormality
Synonyms: Autosomal recessive spondyloepiphyseal dysplasia tarda; PPRD; Progressive Pseudorheumatoid Arthropathy of Childhood; Spondyloepiphyseal dysplasia tarda progressive arthropathy; SPONDYLOEPIPHYSEAL DYSPLASIA TARDA WITH PROGRESSIVE ARTHROPATHY
SNOMED CT: Progressive pseudorheumatoid dysplasia (254065005)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): CCN6 (6q21)
 
Monarch Initiative: MONDO:0008827
OMIM®: 208230
Orphanet: ORPHA1159

Disease characteristics

Excerpted from the GeneReview: Progressive Pseudorheumatoid Dysplasia
Progressive pseudorheumatoid dysplasia (PPD) is a skeletal dysplasia characterized by predominant involvement of articular cartilage with progressive joint stiffness and enlargement in the absence of inflammation. Onset – typically between ages three and six years – begins with the involvement of the interphalangeal joints. Over time, involvement of large joints and the spine causes significant joint contractures, gait disturbance, and scoliosis and/or kyphosis, resulting in abnormal posture and significant morbidity. Despite the considerable arthropathy, pain is not a major presenting feature of this condition. Initially height is normal; however, short stature (<3rd centile) becomes evident in adolescence as the skeletal changes progress. [from GeneReviews]
Authors:
Gandham SriLakshmi Bhavani  |  Hitesh Shah  |  Anju Shukla, et. al.   view full author information

Additional descriptions

From NCBI curation
Progressive pseudorheumatoid dysplasia (PPD) is a skeletal dysplasia characterized by predominant involvement of articular cartilage with progressive joint stiffness and enlargement in the absence of inflammation. Onset – typically between ages three and six years – begins with the involvement of the interphalangeal joints. Over time, involvement of large joints and the spine causes significant joint contractures, gait disturbance, and scoliosis and/or kyphosis, resulting in abnormal posture and significant morbidity. Despite the considerable arthropathy, pain is not a major presenting feature of this condition.
From OMIM
Progressive pseudorheumatoid dysplasia (PPRD) is an autosomal recessive skeletal dysplasia with radiographic changes similar to those of spondyloepiphyseal dysplasia tarda, and clinical, but not radiographic, resemblance to rheumatoid arthritis. It is a progressive chondropathy affecting primarily the articular cartilage with characteristic skeletal abnormalities notably in the spine (summary by El-Shanti et al., 1997). Signs and symptoms, typically consisting of stiffness and swelling of joints, motor weakness, and joint contractures, usually develop between 3 and 8 years of age (summary by Hurvitz et al., 1999).  http://www.omim.org/entry/208230
From MedlinePlus Genetics
Progressive pseudorheumatoid dysplasia (PPRD) is a joint disease that worsens over time. This condition is characterized by breakdown (degeneration) of the cartilage between bones (articular cartilage). This cartilage covers and protects the ends of bones, and its degeneration leads to pain and stiffness in the joints and other features of PPRD.

PPRD usually begins in childhood, between ages 3 and 8. The first indications are usually an abnormal walking pattern, weakness and fatigue when active, and stiffness in the joints in the fingers and in the knees. Other signs and symptoms that develop over time include permanently bent fingers (camptodactyly), enlarged finger and knee joints (often mistaken as swelling), and a reduced amount of space between the bones at the hip and knee joints. Hip pain is a common problem by adolescence. Affected individuals have flattened bones in the spine (platyspondyly) that are abnormally shaped (beaked), which leads to an abnormal front-to-back curvature of the spine (kyphosis) and a short torso. At birth, people with PPRD are of normal length, but by adulthood, they are usually shorter than their peers. Affected adults also have abnormal deposits of calcium around the elbow, knee, and hip joints and limited movement in all joints, including those of the spine.

PPRD is often mistaken for another joint disorder that affects young people called juvenile rheumatoid arthritis. However, the joint problems in juvenile rheumatoid arthritis are associated with inflammation, while those in PPRD are not.  https://medlineplus.gov/genetics/condition/progressive-pseudorheumatoid-dysplasia

Clinical features

From HPO
Genu varum
MedGen UID:
154257
Concept ID:
C0544755
Finding
A positional abnormality marked by outward bowing of the legs in which the knees stay wide apart when a person stands with the feet and ankles together.
Enlarged metacarpophalangeal joints
MedGen UID:
347936
Concept ID:
C1859700
Finding
Enlarged interphalangeal joints
MedGen UID:
347212
Concept ID:
C1859701
Finding
Abnormal foot morphology
MedGen UID:
1762829
Concept ID:
C5399834
Anatomical Abnormality
An abnormality of the skeleton of foot.
Coxa vara
MedGen UID:
1790477
Concept ID:
C5551440
Anatomical Abnormality
Coxa vara includes all forms of decrease of the femoral neck shaft angle (the angle between the neck and the shaft of the femur) to less than 120 degrees.
Waddling gait
MedGen UID:
66667
Concept ID:
C0231712
Finding
Weakness of the hip girdle and upper thigh muscles, for instance in myopathies, leads to an instability of the pelvis on standing and walking. If the muscles extending the hip joint are affected, the posture in that joint becomes flexed and lumbar lordosis increases. The patients usually have difficulties standing up from a sitting position. Due to weakness in the gluteus medius muscle, the hip on the side of the swinging leg drops with each step (referred to as Trendelenburg sign). The gait appears waddling. The patients frequently attempt to counteract the dropping of the hip on the swinging side by bending the trunk towards the side which is in the stance phase (in the German language literature this is referred to as Duchenne sign). Similar gait patterns can be caused by orthopedic conditions when the origin and the insertion site of the gluteus medius muscle are closer to each other than normal, for instance due to a posttraumatic elevation of the trochanter or pseudarthrosis of the femoral neck.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Arthropathy
MedGen UID:
7190
Concept ID:
C0022408
Disease or Syndrome
Any disorder of the joints.
Osteoarthritis
MedGen UID:
45244
Concept ID:
C0029408
Disease or Syndrome
Osteoarthritis (OA) is a degenerative disease of the joints characterized by degradation of the hyaline articular cartilage and remodeling of the subchondral bone with sclerosis (Meulenbelt et al., 2006). Clinical problems include pain and joint stiffness often leading to significant disability and joint replacement. Osteoarthritis exhibits a clear predilection for specific joints; it appears most commonly in the hip and knee joints and lumbar and cervical spine, as well as in the distal interphalangeal and the first carpometacarpal (base of thumb) and proximal interphalangeal joints of the hand; however, patients with osteoarthritis may have 1, a few, or all of these sites affected (Stefansson et al., 2003). According to a conservative estimate, greater than 70% of the population of the United States at age 65 years is affected by the disease, reflecting its age dependence. Genetic Heterogeneity of Susceptibility to Osteoarthritis Susceptibility to osteoarthritis has been associated with variation in other genes: OS2 (140600) with variation in the MATN3 gene (602109) on chromosome 2p24; OS3 (607850) with variation in the ASPN gene (608135) on chromosome 9q22; and OS5 (612400) with variation in the GDF5 gene (601146) on chromosome 20q11. Other susceptibility loci for osteoarthritis have been mapped to chromosomes 2q33 (OS4; 610839) and 3p24 (OS6; 612401).
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Joint swelling
MedGen UID:
56258
Concept ID:
C0152031
Finding
The presence of swelling in a joint.
Joint contracture of the hand
MedGen UID:
56382
Concept ID:
C0158113
Finding
Contractures of one ore more joints of the hands meaning chronic loss of joint motion due to structural changes in non-bony tissue.
Joint stiffness
MedGen UID:
56403
Concept ID:
C0162298
Sign or Symptom
Joint stiffness is a perceived sensation of tightness in a joint or joints when attempting to move them after a period of inactivity. Joint stiffness typically subsides over time.
Camptodactyly of finger
MedGen UID:
98041
Concept ID:
C0409348
Finding
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers cannot be extended to 180 degrees by either active or passive extension.
Kyphoscoliosis
MedGen UID:
154361
Concept ID:
C0575158
Anatomical Abnormality
An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.
Enlarged epiphyses
MedGen UID:
318846
Concept ID:
C1833328
Finding
Increased size of epiphyses.
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
Metaphyseal widening
MedGen UID:
341364
Concept ID:
C1849039
Finding
Abnormal widening of the metaphyseal regions of long bones.
Flattened epiphysis
MedGen UID:
387844
Concept ID:
C1857527
Finding
Abnormal flatness (decreased height) of epiphyses.
Decreased cervical spine mobility
MedGen UID:
395323
Concept ID:
C1859692
Finding
Enlargement of the proximal femoral epiphysis
MedGen UID:
347210
Concept ID:
C1859697
Finding
An abnormal enlargement of the proximal epiphysis of the femur.
Sclerotic vertebral endplates
MedGen UID:
1642576
Concept ID:
C4551970
Finding
Sclerosis (increased density) affecting vertebral end plates.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVProgressive pseudorheumatoid dysplasia
Follow this link to review classifications for Progressive pseudorheumatoid dysplasia in Orphanet.

Professional guidelines

PubMed

Wang W, Gao SH, Wei M, Zhong LQ, Liu W, Jian S, Xiao J, Zhang CH, Zhang JG, Zeng XF, Xia WB, Qiu ZQ, Song HM
World J Pediatr 2023 Jul;19(7):674-686. Epub 2023 Jan 9 doi: 10.1007/s12519-022-00674-7. PMID: 36622578Free PMC Article
Yin L, Mao Y, Zhou Y, Shen Y, Chen H, Zhou W, Jin Y, Huang H, Yu Y, Wang J
Clin Rheumatol 2022 Mar;41(3):877-888. Epub 2021 Oct 21 doi: 10.1007/s10067-021-05959-2. PMID: 34674084

Recent clinical studies

Etiology

Wang W, Gao SH, Wei M, Zhong LQ, Liu W, Jian S, Xiao J, Zhang CH, Zhang JG, Zeng XF, Xia WB, Qiu ZQ, Song HM
World J Pediatr 2023 Jul;19(7):674-686. Epub 2023 Jan 9 doi: 10.1007/s12519-022-00674-7. PMID: 36622578Free PMC Article
Uludağ Alkaya D, Kasapçopur Ö, Bursalı A, Adrovic A, Demir B, Aykut A, Tüysüz B
Rheumatology (Oxford) 2022 Aug 30;61(9):3693-3703. doi: 10.1093/rheumatology/keab926. PMID: 34919662
Yin L, Mao Y, Zhou Y, Shen Y, Chen H, Zhou W, Jin Y, Huang H, Yu Y, Wang J
Clin Rheumatol 2022 Mar;41(3):877-888. Epub 2021 Oct 21 doi: 10.1007/s10067-021-05959-2. PMID: 34674084
Feng B, Xiao K, Ren Y, Xia Z, Jin J, Wu Z, Qiu G, Weng X
J Clin Rheumatol 2021 Jun 1;27(4):156-160. doi: 10.1097/RHU.0000000000001248. PMID: 31876842
el-Shanti HE, Omari HZ, Qubain HI
J Med Genet 1997 Jul;34(7):559-63. doi: 10.1136/jmg.34.7.559. PMID: 9222963Free PMC Article

Diagnosis

Wang W, Xiao G, Han Q, Ding J, Xie R, Jia J, Leng N, Zheng Z
Medicine (Baltimore) 2023 Jul 7;102(27):e34099. doi: 10.1097/MD.0000000000034099. PMID: 37417608Free PMC Article
El Dessouki D, Amr K, Kholoussi N, Rady HM, Temtamy SA, Abdou MMS, Aglan M
Am J Med Genet A 2023 Sep;191(9):2329-2336. Epub 2023 Jun 28 doi: 10.1002/ajmg.a.63339. PMID: 37377052
Pomeranz CB, Reid JR
Skeletal Radiol 2019 Sep;48(9):1323-1328. Epub 2019 Feb 2 doi: 10.1007/s00256-019-3165-z. PMID: 30712121
Torreggiani S, Torcoletti M, Campos-Xavier B, Baldo F, Agostoni C, Superti-Furga A, Filocamo G
Rheumatol Int 2019 Mar;39(3):441-452. Epub 2018 Oct 16 doi: 10.1007/s00296-018-4170-6. PMID: 30327864
Garcia Segarra N, Mittaz L, Campos-Xavier AB, Bartels CF, Tuysuz B, Alanay Y, Cimaz R, Cormier-Daire V, Di Rocco M, Duba HC, Elcioglu NH, Forzano F, Hospach T, Kilic E, Kuemmerle-Deschner JB, Mortier G, Mrusek S, Nampoothiri S, Obersztyn E, Pauli RM, Selicorni A, Tenconi R, Unger S, Utine GE, Wright M, Zabel B, Warman ML, Superti-Furga A, Bonafé L
Am J Med Genet C Semin Med Genet 2012 Aug 15;160C(3):217-29. Epub 2012 Jul 12 doi: 10.1002/ajmg.c.31333. PMID: 22791401

Therapy

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Prognosis

Uludağ Alkaya D, Kasapçopur Ö, Bursalı A, Adrovic A, Demir B, Aykut A, Tüysüz B
Rheumatology (Oxford) 2022 Aug 30;61(9):3693-3703. doi: 10.1093/rheumatology/keab926. PMID: 34919662
Feng B, Xiao K, Ren Y, Xia Z, Jin J, Wu Z, Qiu G, Weng X
J Clin Rheumatol 2021 Jun 1;27(4):156-160. doi: 10.1097/RHU.0000000000001248. PMID: 31876842
Pode-Shakked B, Vivante A, Barel O, Padeh S, Marek-Yagel D, Veber A, Abudi S, Eliyahu A, Tirosh I, Shpilman S, Shril S, Hildebrandt F, Shohat M, Anikster Y
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Chen W, Mo S, Luo G, Wang Y, Deng X, Zhu J, Zhao W
Pediatr Rheumatol Online J 2018 Sep 10;16(1):55. doi: 10.1186/s12969-018-0272-7. PMID: 30200995Free PMC Article
Sailani MR, Chappell J, Jingga I, Narasimha A, Zia A, Lynch JL, Mazrouei S, Bernstein JA, Aryani O, Snyder MP
Cold Spring Harb Mol Case Stud 2018 Feb;4(1) Epub 2018 Feb 1 doi: 10.1101/mcs.a001990. PMID: 29092958Free PMC Article

Clinical prediction guides

Uludağ Alkaya D, Kasapçopur Ö, Bursalı A, Adrovic A, Demir B, Aykut A, Tüysüz B
Rheumatology (Oxford) 2022 Aug 30;61(9):3693-3703. doi: 10.1093/rheumatology/keab926. PMID: 34919662
Greer SY, Bullion EA
Int J Paleopathol 2021 Sep;34:147-154. Epub 2021 Jul 13 doi: 10.1016/j.ijpp.2021.06.009. PMID: 34271408
Feng B, Xiao K, Ren Y, Xia Z, Jin J, Wu Z, Qiu G, Weng X
J Clin Rheumatol 2021 Jun 1;27(4):156-160. doi: 10.1097/RHU.0000000000001248. PMID: 31876842
Lin LJ, Ge YM, Tian Y, Liu N, Luo XH, Xue YT, Xue YZB, Wen CY, Tang B
Clin Biomech (Bristol, Avon) 2020 Oct;79:104947. Epub 2020 Jan 2 doi: 10.1016/j.clinbiomech.2019.12.029. PMID: 31959394
Sailani MR, Chappell J, Jingga I, Narasimha A, Zia A, Lynch JL, Mazrouei S, Bernstein JA, Aryani O, Snyder MP
Cold Spring Harb Mol Case Stud 2018 Feb;4(1) Epub 2018 Feb 1 doi: 10.1101/mcs.a001990. PMID: 29092958Free PMC Article

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