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Hypertrophic osteoarthropathy, primary, autosomal recessive, 2(PHOAR2E)

MedGen UID:
482430
Concept ID:
C3280800
Disease or Syndrome
Synonyms: HYPERTROPHIC OSTEOARTHROPATHY, PRIMARY, AUTOSOMAL RECESSIVE, 2/ENTEROPATHY SYNDROME; PACHYDERMOPERIOSTOSIS, AUTOSOMAL RECESSIVE; PDP, AUTOSOMAL RECESSIVE; PHOAR2-ENTEROPATHY SYNDROME; PHOAR2E
 
Gene (location): SLCO2A1 (3q22.1-22.2)
 
Monarch Initiative: MONDO:0013756
OMIM®: 614441

Definition

PHOAR2-enteropathy syndrome (PHOAR2E) is characterized by primary hypertrophic osteoarthropathy (PHO) and/or chronic nonspecific ulcers (CNSU) of the small intestine. The cardinal features of PHO are digital clubbing, pachydermia, and periostosis; other manifestations include swelling and pain of the large joints, hyperhidrosis, seborrhea, and acne. CNSU often presents with chronic unexplained anemia and abdominal pain, and patients may exhibit edema due to hypoalbuminemia. Radiologic imaging or endoscopy shows multiple small ulcers, predominantly in the ileum, although the stomach, duodenum, and jejunum are often involved. PHO is more frequent and more severe in male patients, who often also report watery diarrhea, whereas CNSU is more often diagnosed in female patients, who may also show features of PHO such as digital clubbing or arthralgias and swelling of the joints. The same mutations in the SLCO2A1 gene have been reported in patients presenting with either diagnosis, and presumed sex-related modifiers of the manifestations of disease or other genotype/phenotype correlates have yet to be elucidated (Li et al., 2017; Umeno et al., 2018; Hong et al., 2022; Kimball et al., 2024). For a discussion of genetic heterogeneity of PHO, see PHOAR1 (259100). [from OMIM]

Clinical features

From HPO
Knee pain
MedGen UID:
65421
Concept ID:
C0231749
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the knee.
Clubbing
MedGen UID:
57692
Concept ID:
C0149651
Anatomical Abnormality
Broadening of the soft tissues (non-edematous swelling of soft tissues) of the digital tips in all dimensions associated with an increased longitudinal and lateral curvature of the nails.
Secretory diarrhea
MedGen UID:
75635
Concept ID:
C0267557
Disease or Syndrome
Watery voluminous diarrhea resulting from an imbalance between ion and water secretion and absorption.
Hyperostosis
MedGen UID:
9366
Concept ID:
C0020492
Disease or Syndrome
Excessive growth or abnormal thickening of bone tissue.
Periostosis
MedGen UID:
473416
Concept ID:
C1409412
Disease or Syndrome
Abnormal deposition of periosteal bone.
Seborrheic dermatitis
MedGen UID:
19912
Concept ID:
C0036508
Disease or Syndrome
Seborrheic dermatitis is a form of eczema which is closely related to dandruff. It causes dry or greasy peeling of the scalp, eyebrows, and face, and sometimes trunk.
Acne
MedGen UID:
152379
Concept ID:
C0702166
Disease or Syndrome
A skin condition in which there is an increase in sebum secretion by the pilosebaceous apparatus associated with open comedones (blackheads), closed comedones (whiteheads), and pustular nodules (papules, pustules, and cysts).
Hypoalbuminemia
MedGen UID:
68694
Concept ID:
C0239981
Finding
Reduction in the concentration of albumin in the blood.
Hyperhidrosis
MedGen UID:
5690
Concept ID:
C0020458
Finding
Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather.
Thickened skin
MedGen UID:
66024
Concept ID:
C0241165
Finding
Laminar thickening of skin.

Professional guidelines

PubMed

Guan Y, Deng H, Dong Q, Wang J
Aesthetic Plast Surg 2024 Jul;48(13):2375-2381. Epub 2024 May 21 doi: 10.1007/s00266-024-04073-3. PMID: 38772942
Lu Q, Xu Y, Zhang Z, Li S, Zhang Z
Front Endocrinol (Lausanne) 2023;14:1235040. Epub 2023 Aug 29 doi: 10.3389/fendo.2023.1235040. PMID: 37705574Free PMC Article

Recent clinical studies

Etiology

Pang Q, Xu Y, Liao R, Li Y, Zhang L, Chi Y, Qi X, Li M, Jiang Y, Wang O, Xing X, Qin L, Xia W
Osteoporos Int 2023 Aug;34(8):1453-1464. Epub 2023 May 18 doi: 10.1007/s00198-023-06784-w. PMID: 37202541Free PMC Article
Ma GM, Chow JS, Taylor GA
Pediatr Radiol 2019 Apr;49(4):534-550. Epub 2019 Mar 16 doi: 10.1007/s00247-019-04371-y. PMID: 30877339
van Manen MJG, Vermeer LC, Moor CC, Vrijenhoeff R, Grutters JC, Veltkamp M, Wijsenbeek MS
Respir Med 2017 Nov;132:226-231. Epub 2017 Nov 2 doi: 10.1016/j.rmed.2017.10.021. PMID: 29229102
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Diagnosis

Lu Q, Xu Y, Zhang Z, Li S, Zhang Z
Front Endocrinol (Lausanne) 2023;14:1235040. Epub 2023 Aug 29 doi: 10.3389/fendo.2023.1235040. PMID: 37705574Free PMC Article
Ikeda K, Miyamori D, Hirabayashi R, Ito M
QJM 2022 Sep 22;115(9):611-612. doi: 10.1093/qjmed/hcac147. PMID: 35731213
Ma GM, Chow JS, Taylor GA
Pediatr Radiol 2019 Apr;49(4):534-550. Epub 2019 Mar 16 doi: 10.1007/s00247-019-04371-y. PMID: 30877339
Doshi D
Orbit 2018 Apr;37(2):97-101. Epub 2017 Oct 17 doi: 10.1080/01676830.2017.1383459. PMID: 29040027
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Therapy

Joshi A, Nepal G, Shing YK, Panthi HP, Baral S
J Med Case Rep 2019 Feb 21;13(1):39. doi: 10.1186/s13256-018-1961-z. PMID: 30786934Free PMC Article
Li SS, He JW, Fu WZ, Liu YJ, Hu YQ, Zhang ZL
J Bone Miner Res 2017 Aug;32(8):1659-1666. Epub 2017 Jun 2 doi: 10.1002/jbmr.3157. PMID: 28425581
Nguyen S, Hojjati M
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Med Clin North Am 1986 Mar;70(2):385-417. doi: 10.1016/s0025-7125(16)30960-9. PMID: 2936936

Prognosis

van Manen MJG, Vermeer LC, Moor CC, Vrijenhoeff R, Grutters JC, Veltkamp M, Wijsenbeek MS
Respir Med 2017 Nov;132:226-231. Epub 2017 Nov 2 doi: 10.1016/j.rmed.2017.10.021. PMID: 29229102
Cheng R, Li M, Guo Y, Yao Y, Gao C, Yao Z
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Ihde DC, Minna JD
Curr Probl Cancer 1991 Mar-Apr;15(2):61-104. doi: 10.1016/0147-0272(91)90014-2. PMID: 1649734

Clinical prediction guides

Hong HS, Baek J, Park JC, Lee HS, Park D, Yoon AR, Park SJ, Hong SN, Koh SJ, Lee CK, Lee BI, Hwang SW, Park SH, Myung SJ, Yang SK, Song K, Ye BD; IBD Research Group of the Korean Association for the Study of Intestinal Diseases
Gut Liver 2022 Nov 15;16(6):942-951. Epub 2022 May 25 doi: 10.5009/gnl210415. PMID: 35611666Free PMC Article
Xu Y, Zhang Z, Yue H, Li S, Zhang Z
J Bone Miner Res 2021 Aug;36(8):1459-1468. Epub 2021 May 5 doi: 10.1002/jbmr.4310. PMID: 33852188
van Manen MJG, Vermeer LC, Moor CC, Vrijenhoeff R, Grutters JC, Veltkamp M, Wijsenbeek MS
Respir Med 2017 Nov;132:226-231. Epub 2017 Nov 2 doi: 10.1016/j.rmed.2017.10.021. PMID: 29229102
Cheng R, Li M, Guo Y, Yao Y, Gao C, Yao Z
Eur J Dermatol 2013 Sep-Oct;23(5):636-9. doi: 10.1684/ejd.2013.2154. PMID: 24153155
Santiago MB, Lima I, Feitosa AC, Braz Ade S, Miranda LG
Semin Arthritis Rheum 2009 Jun;38(6):452-7. Epub 2008 Apr 18 doi: 10.1016/j.semarthrit.2008.01.018. PMID: 18378280

Recent systematic reviews

Palui R, Sridharan K, Sahoo J, Suryadevara V, Kamalanathan S, Naik D, Halanaik D, Durgia H, Raj H
Endocrine 2024 Aug;85(2):883-893. Epub 2024 Apr 2 doi: 10.1007/s12020-024-03804-5. PMID: 38564085
Wang Q, Li YH, Lin GL, Li Y, Zhou WX, Qian JM, Xia WB, Wu D
Orphanet J Rare Dis 2019 Dec 26;14(1):297. doi: 10.1186/s13023-019-1264-5. PMID: 31878983Free PMC Article

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