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Enlargement of the wrists

MedGen UID:
325479
Concept ID:
C1838663
Finding
HPO: HP:0003020

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVEnlargement of the wrists

Conditions with this feature

Vitamin D-dependent rickets, type 1
MedGen UID:
124344
Concept ID:
C0268689
Disease or Syndrome
Vitamin D-dependent rickets is a disorder of bone development that leads to softening and weakening of the bones (rickets). There are several forms of the condition that are distinguished primarily by their genetic causes: type 1A (VDDR1A), type 1B (VDDR1B), and type 2A (VDDR2A). There is also evidence of a very rare form of the condition, called type 2B (VDDR2B), although not much is known about this form.\n\nThe signs and symptoms of vitamin D-dependent rickets begin within months after birth, and most are the same for all types of the condition. The weak bones often cause bone pain and delayed growth and have a tendency to fracture. When affected children begin to walk, they may develop abnormally curved (bowed) legs because the bones are too weak to bear weight. Impaired bone development also results in widening of the areas near the ends of bones where new bone forms (metaphyses), especially in the knees, wrists, and ribs. Some people with vitamin D-dependent rickets have dental abnormalities such as thin tooth enamel and frequent cavities. Poor muscle tone (hypotonia) and muscle weakness are also common in this condition, and some affected individuals develop seizures.\n\nIn vitamin D-dependent rickets, there is an imbalance of certain substances in the blood. An early sign in all types of the condition is low levels of the mineral calcium (hypocalcemia), which is essential for the normal formation of bones and teeth. Affected individuals also develop high levels of a hormone involved in regulating calcium levels called parathyroid hormone (PTH), which leads to a condition called secondary hyperparathyroidism. Low levels of a mineral called phosphate (hypophosphatemia) also occur in affected individuals. Vitamin D-dependent rickets types 1 and 2 can be grouped by blood levels of a hormone called calcitriol, which is the active form of vitamin D; individuals with VDDR1A and VDDR1B have abnormally low levels of calcitriol and individuals with VDDR2A and VDDR2B have abnormally high levels.\n\nHair loss (alopecia) can occur in VDDR2A, although not everyone with this form of the condition has alopecia. Affected individuals can have sparse or patchy hair or no hair at all on their heads. Some affected individuals are missing body hair as well.
Vitamin D-dependent rickets type II with alopecia
MedGen UID:
90989
Concept ID:
C0342646
Disease or Syndrome
Vitamin D-dependent rickets type 2A (VDDR2A) is caused by a defect in the vitamin D receptor gene. This defect leads to an increase in the circulating ligand, 1,25-dihydroxyvitamin D3. Most patients have total alopecia in addition to rickets. VDDR2B (600785) is a form of vitamin D-dependent rickets with a phenotype similar to VDDR2A but a normal vitamin D receptor, in which end-organ resistance to vitamin D has been shown to be caused by a nuclear ribonucleoprotein that interferes with the vitamin D receptor-DNA interaction. For a general phenotypic description and a discussion of genetic heterogeneity of rickets due to disorders in vitamin D metabolism or action, see vitamin D-dependent rickets type 1A (VDDR1A; 264700).
Vitamin D hydroxylation-deficient rickets, type 1B
MedGen UID:
374020
Concept ID:
C1838657
Disease or Syndrome
Vitamin D hydroxylation-deficient rickets type 1B (VDDR1B) is caused by a defect in vitamin D 25-hydroxylation (Molin et al., 2017). The major function of vitamin D is to maintain calcium and phosphate levels in the normal range to support metabolic functions, neuromuscular transmission, and bone mineralization. Disorders of vitamin D metabolism or action lead to defective bone mineralization and clinical features including intestinal malabsorption of calcium, hypocalcemia, secondary hyperparathyroidism, increased renal clearance of phosphorus, and hypophosphatemia. The combination of hypocalcemia and hypophosphatemia causes impaired mineralization of bone that results in rickets and osteomalacia (summary by Liberman and Marx, 2001). Rickets can occur because of inadequate dietary intake or sun exposure or because of genetic disorders. Vitamin D3 (cholecalciferol) is taken in the diet or synthesized in the skin from 7-dehydrocholesterol by ultraviolet irradiation. For vitamin D to be active, it needs to be converted to its active form, 1,25-dihydroxyvitamin D3. Vitamin D is transported in the blood by the vitamin D binding protein (DBP; 139200) to the liver, where vitamin D 25-hydroxylase (CYP2R1; 608713) is the key enzyme for 25-hydroxylation. Vitamin D 25(OH)D3, the major circulating form of vitamin D, is then transported to the kidney, where 25(OH)D3 is hydroxylated at the position of carbon 1 of the A ring, resulting in the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) (summary by Christakos et al., 2010).
Hypophosphatemic rickets, X-linked recessive
MedGen UID:
335115
Concept ID:
C1845168
Disease or Syndrome
X-linked recessive hypophosphatemic rickets (XLHRR) is a form of X-linked hypercalciuric nephrolithiasis, which comprises a group of disorders characterized by proximal renal tubular reabsorptive failure, hypercalciuria, nephrocalcinosis, and renal insufficiency. These disorders have also been referred to as the 'Dent disease complex' (Scheinman, 1998; Gambaro et al., 2004). For a general discussion of Dent disease, see 300009.
Dent disease type 1
MedGen UID:
336322
Concept ID:
C1848336
Disease or Syndrome
Dent disease, an X-linked disorder of proximal renal tubular dysfunction, is characterized by low molecular weight (LMW) proteinuria, hypercalciuria, and at least one additional finding including nephrocalcinosis, nephrolithiasis, hematuria, hypophosphatemia, chronic kidney disease (CKD), and evidence of X-linked inheritance. Males younger than age ten years may manifest only LMW proteinuria and/or hypercalciuria, which are usually asymptomatic. Thirty to 80% of affected males develop end-stage renal disease (ESRD) between ages 30 and 50 years; in some instances ESRD does not develop until the sixth decade of life or later. The disease may also be accompanied by rickets or osteomalacia, growth restriction, and short stature. Disease severity can vary within the same family. Males with Dent disease 2 (caused by pathogenic variants in OCRL) may also have mild intellectual disability, cataracts, and/or elevated muscle enzymes. Due to random X-chromosome inactivation, some female carriers may manifest hypercalciuria and, rarely, renal calculi and moderate LMW proteinuria. Females rarely develop CKD.
Autosomal recessive hypophosphatemic bone disease
MedGen UID:
501133
Concept ID:
C1853271
Disease or Syndrome
Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare autosomal recessive disorder characterized by the presence of hypophosphatemia secondary to renal phosphate wasting, radiographic and/or histologic evidence of rickets, limb deformities, muscle weakness, and bone pain. HHRH is distinct from other forms of hypophosphatemic rickets in that affected individuals present with hypercalciuria due to increased serum 1,25-dihydroxyvitamin D levels and increased intestinal calcium absorption (summary by Bergwitz et al., 2006).

Professional guidelines

PubMed

Ji JJ, Lin Y, Huang SS, Zhang HL, Diao YP, Li K
Afr J Tradit Complement Altern Med 2013;10(3):418-21. Epub 2013 Apr 12 PMID: 24146468Free PMC Article
Tahiri Y, Xu L, Kanevsky J, Luc M
J Hand Surg Am 2013 Oct;38(10):2055-67. Epub 2013 May 17 doi: 10.1016/j.jhsa.2013.03.022. PMID: 23684521
Cartwright MS, Hobson-Webb LD, Boon AJ, Alter KE, Hunt CH, Flores VH, Werner RA, Shook SJ, Thomas TD, Primack SJ, Walker FO; American Association of Neuromuscular and Electrodiagnostic Medicine
Muscle Nerve 2012 Aug;46(2):287-93. doi: 10.1002/mus.23389. PMID: 22806381

Recent clinical studies

Etiology

Tran CT, Smet ME, Forsey J, Zankl A, Nayyar R
Fetal Diagn Ther 2022;49(11-12):479-485. Epub 2022 Dec 7 doi: 10.1159/000527594. PMID: 36476632
Pelosi L, Arányi Z, Beekman R, Bland J, Coraci D, Hobson-Webb LD, Padua L, Podnar S, Simon N, van Alfen N, Verhamme C, Visser L, Walker FO, Shik Yoon J, Cartwright MS
Clin Neurophysiol 2022 Mar;135:107-116. Epub 2022 Jan 6 doi: 10.1016/j.clinph.2021.12.012. PMID: 35074720
Ceccarelli F, Spinelli FR, Garufi C, Mancuso S, Alessandri C, Di Franco M, Orefice V, Pacucci VA, Pirone C, Priori R, Riccieri V, Sili Scavalli A, Scrivo R, Truglia S, Conti F
Clin Exp Rheumatol 2022 May;40(5):921-927. Epub 2021 Jun 26 doi: 10.55563/clinexprheumatol/totvyv. PMID: 34251313
Henry BM, Zwinczewska H, Roy J, Vikse J, Ramakrishnan PK, Walocha JA, Tomaszewski KA
PLoS One 2015;10(8):e0136477. Epub 2015 Aug 25 doi: 10.1371/journal.pone.0136477. PMID: 26305098Free PMC Article
Prentice A
J Steroid Biochem Mol Biol 2013 Jul;136:201-6. Epub 2012 Dec 7 doi: 10.1016/j.jsbmb.2012.11.018. PMID: 23220549

Diagnosis

Singh D, Rawat R, Thakur V
Skinmed 2022;20(4):311-313. Epub 2022 Aug 31 PMID: 35976025
Lin TY, Chang KV, Wu WT, Özçakar L
J Neurol 2022 Sep;269(9):4663-4675. Epub 2022 May 31 doi: 10.1007/s00415-022-11201-z. PMID: 35639198
Yang T, Deng W, Chu X, Wang X, Hu Y, Fan X, Song J, Gao Y, Zhang B, Tian G, Xiong D, Zhong S, Tang L, Hu Y, Yang W
ACS Nano 2021 Jul 27;15(7):11555-11563. Epub 2021 Jun 15 doi: 10.1021/acsnano.1c01606. PMID: 34128640
Hobson-Webb LD, Juel VC
Continuum (Minneap Minn) 2017 Apr;23(2, Selected Topics in Outpatient Neurology):487-511. doi: 10.1212/CON.0000000000000452. PMID: 28375915
Saigal R, Chaudhary A, Pathak P, Singh A, Gupta D, Tank ML
J Assoc Physicians India 2016 Mar;64(3):88-89. PMID: 27731569

Therapy

Ceccarelli F, Spinelli FR, Garufi C, Mancuso S, Alessandri C, Di Franco M, Orefice V, Pacucci VA, Pirone C, Priori R, Riccieri V, Sili Scavalli A, Scrivo R, Truglia S, Conti F
Clin Exp Rheumatol 2022 May;40(5):921-927. Epub 2021 Jun 26 doi: 10.55563/clinexprheumatol/totvyv. PMID: 34251313
Li R, Wan Q, Chen P, Mao S, Wang Q, Li X, Yang Y, Dong L
Rheumatol Int 2020 Jul;40(7):1143-1149. Epub 2020 Apr 28 doi: 10.1007/s00296-020-04588-3. PMID: 32347340
Nessrine A, Siham D, Meryem B, Samira EF, Taoufik H
Curr Rheumatol Rev 2019;15(4):312-315. doi: 10.2174/1573397115666181231115233. PMID: 30599109
Yim ES, Corrado G
Curr Sports Med Rep 2012 Nov-Dec;11(6):298-303. doi: 10.1249/JSR.0b013e318272c89b. PMID: 23147017
Klett R, Lange U, Haas H, Voth M, Pinkert J
Rheumatology (Oxford) 2007 Oct;46(10):1531-7. Epub 2007 Jun 27 doi: 10.1093/rheumatology/kem155. PMID: 17596287

Prognosis

Tran CT, Smet ME, Forsey J, Zankl A, Nayyar R
Fetal Diagn Ther 2022;49(11-12):479-485. Epub 2022 Dec 7 doi: 10.1159/000527594. PMID: 36476632
Chompoopong P, Niu Z, Shouman K, Madigan NN, Sandroni P, Berini SE, Shin AY, Brault JS, Boon AJ, Laughlin RS, Thorland E, Mandrekar J, Klein CJ
Muscle Nerve 2022 Oct;66(4):479-486. Epub 2022 Aug 11 doi: 10.1002/mus.27687. PMID: 35894586
Ceccarelli F, Spinelli FR, Garufi C, Mancuso S, Alessandri C, Di Franco M, Orefice V, Pacucci VA, Pirone C, Priori R, Riccieri V, Sili Scavalli A, Scrivo R, Truglia S, Conti F
Clin Exp Rheumatol 2022 May;40(5):921-927. Epub 2021 Jun 26 doi: 10.55563/clinexprheumatol/totvyv. PMID: 34251313
Henry BM, Zwinczewska H, Roy J, Vikse J, Ramakrishnan PK, Walocha JA, Tomaszewski KA
PLoS One 2015;10(8):e0136477. Epub 2015 Aug 25 doi: 10.1371/journal.pone.0136477. PMID: 26305098Free PMC Article
Rodriguez Merchan EC
Int Orthop 1995;19(4):255-60. doi: 10.1007/BF00185235. PMID: 8557426

Clinical prediction guides

Tran CT, Smet ME, Forsey J, Zankl A, Nayyar R
Fetal Diagn Ther 2022;49(11-12):479-485. Epub 2022 Dec 7 doi: 10.1159/000527594. PMID: 36476632
Ceccarelli F, Spinelli FR, Garufi C, Mancuso S, Alessandri C, Di Franco M, Orefice V, Pacucci VA, Pirone C, Priori R, Riccieri V, Sili Scavalli A, Scrivo R, Truglia S, Conti F
Clin Exp Rheumatol 2022 May;40(5):921-927. Epub 2021 Jun 26 doi: 10.55563/clinexprheumatol/totvyv. PMID: 34251313
Fairchild R, Horomanski A, Sharpless L, Chung M, Li S, Hong J, Sheth K, Chung L
Semin Arthritis Rheum 2021 Aug;51(4):735-740. Epub 2021 May 8 doi: 10.1016/j.semarthrit.2021.04.020. PMID: 34144383Free PMC Article
Brites L, Santiago M, Rovisco J, Freitas J, A P Silva J, Silva I, Teixeira F, Faria DS, Silva CG, Falcão S
J Clin Rheumatol 2021 Dec 1;27(8):e367-e370. doi: 10.1097/RHU.0000000000001440. PMID: 32568948
Lins CF, Santiago MB
Eur Radiol 2015 Sep;25(9):2688-92. Epub 2015 Feb 27 doi: 10.1007/s00330-015-3670-y. PMID: 25716942

Recent systematic reviews

Abdelnaby R, ELgenidy A, Mohamed KA, Sonbol YT, Elwshahi MM, Elnouty MM, Aboutaleb AM, Ebrahim MA, Dardeer KT, Heikal HA, Gawish HM, Cartwright MS
Muscle Nerve 2023 Mar;67(3):217-225. Epub 2022 Dec 31 doi: 10.1002/mus.27773. PMID: 36533969
Chen IJ, Chang KV, Wu WT, Özçakar L
Arch Phys Med Rehabil 2019 Jun;100(6):1114-1130. Epub 2018 Jul 25 doi: 10.1016/j.apmr.2018.06.021. PMID: 30055161
Henry BM, Zwinczewska H, Roy J, Vikse J, Ramakrishnan PK, Walocha JA, Tomaszewski KA
PLoS One 2015;10(8):e0136477. Epub 2015 Aug 25 doi: 10.1371/journal.pone.0136477. PMID: 26305098Free PMC Article
Lins CF, Santiago MB
Eur Radiol 2015 Sep;25(9):2688-92. Epub 2015 Feb 27 doi: 10.1007/s00330-015-3670-y. PMID: 25716942
Tahiri Y, Xu L, Kanevsky J, Luc M
J Hand Surg Am 2013 Oct;38(10):2055-67. Epub 2013 May 17 doi: 10.1016/j.jhsa.2013.03.022. PMID: 23684521

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