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Hypertrophic osteoarthropathy, primary, autosomal recessive, 1(PHOAR1)

MedGen UID:
1641972
Concept ID:
C4551679
Disease or Syndrome
Synonyms: PHO, AUTOSOMAL RECESSIVE; PHOAR1; Primary Hypertrophic Osteoarthropathy, Autosomal Recessive
 
Gene (location): HPGD (4q34.1)
 
Monarch Initiative: MONDO:0024546
OMIM®: 259100

Definition

Autosomal recessive primary hypertrophic osteoarthropathy-1 (PHOAR1) is a rare familial disorder characterized by digital clubbing, osteoarthropathy, and acroosteolysis, with variable features of pachydermia, delayed closure of the fontanels, and congenital heart disease (summary by Uppal et al., 2008; Radhakrishnan et al., 2020). Secondary hypertrophic osteoarthropathy, or pulmonary hypertrophic osteoarthropathy, is a different disorder characterized by digital clubbing secondary to acquired diseases, most commonly intrathoracic neoplasm (Uppal et al., 2008). Touraine et al. (1935) recognized pachydermoperiostosis as a familial disorder with 3 clinical presentations or forms: a complete form characterized by periostosis and pachydermia; an incomplete form with bone changes but without pachydermia; and a 'forme fruste' with pachydermia and minimal skeletal changes. Genetic Heterogeneity Autosomal recessive primary hypertrophic osteoarthropathy-2-enteropathy syndrome (PHOAR2E; 614441) is caused by mutation in the SLCO2A1 gene (601460) on chromosome 3q22. Families with an autosomal dominant form of primary hypertrophic osteoarthropathy have also been reported (PHOAD; 167100). [from OMIM]

Clinical features

From HPO
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Palmoplantar keratosis
MedGen UID:
44017
Concept ID:
C0022596
Disease or Syndrome
Abnormal thickening of the skin localized to the palm of the hand and the sole of the foot.
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.
Acroosteolysis
MedGen UID:
183017
Concept ID:
C0917990
Disease or Syndrome
Dissolution or degeneration of bone tissue of the phalanges of the hand.
Patent ductus arteriosus
MedGen UID:
4415
Concept ID:
C0013274
Congenital Abnormality
In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.
Disproportionate tall stature
MedGen UID:
323048
Concept ID:
C1836996
Finding
A tall and slim body build with increased arm span to height ratio (>1.05) and a reduced upper-to-lower segment ratio (<0.85), i.e., unusually long arms and legs. The extremities as well as the hands and feet are unusually slim.
Arthritis
MedGen UID:
2043
Concept ID:
C0003864
Disease or Syndrome
Inflammation of a joint.
Arthropathy
MedGen UID:
7190
Concept ID:
C0022408
Disease or Syndrome
Any disorder of the joints.
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
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).
Long clavicles
MedGen UID:
96530
Concept ID:
C0426808
Finding
Increased length of the clavicles.
Large fontanelles
MedGen UID:
105329
Concept ID:
C0456132
Finding
In newborns, the two frontal bones, two parietal bones, and one occipital bone are joined by fibrous sutures, which form a small posterior fontanelle, and a larger, diamond-shaped anterior fontanelle. These regions allow for the skull to pass the birth canal and for later growth. The fontanelles gradually ossify, whereby the posterior fontanelle usually closes by eight weeks and the anterior fontanelle by the 9th to 16th month of age. Large fontanelles are diagnosed if the fontanelles are larger than age-dependent norms.
Limitation of joint mobility
MedGen UID:
341696
Concept ID:
C1857108
Finding
A reduction in the freedom of movement of one or more joints.
Thickened calvaria
MedGen UID:
346823
Concept ID:
C1858452
Finding
The presence of an abnormally thick calvaria.
Pectus excavatum
MedGen UID:
781174
Concept ID:
C2051831
Finding
A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance.
Wormian bones
MedGen UID:
766814
Concept ID:
C3553900
Congenital Abnormality
The presence of extra bones within a cranial suture. Wormian bones are irregular isolated bones which appear in addition to the usual centers of ossification of the cranium.
Eczema
MedGen UID:
3968
Concept ID:
C0013595
Disease or Syndrome
Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces.
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.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Flushing
MedGen UID:
5234
Concept ID:
C0016382
Sign or Symptom
Recurrent episodes of redness of the skin together with a sensation of warmth or burning of the affected areas of skin.
Hyperhidrosis
MedGen UID:
5690
Concept ID:
C0020458
Finding
Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather.
Erythema
MedGen UID:
11999
Concept ID:
C0041834
Disease or Syndrome
Redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin.
Redundant skin
MedGen UID:
154379
Concept ID:
C0581342
Pathologic Function
Loose and sagging skin often associated with loss of skin elasticity.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHypertrophic osteoarthropathy, primary, autosomal recessive, 1

Professional guidelines

PubMed

Limenis E, Stimec J, Kannu P, Laxer RM
Pediatr Rheumatol Online J 2021 Jul 14;19(1):113. doi: 10.1186/s12969-021-00596-0. PMID: 34261502Free PMC Article
Giancane G, Diggle CP, Legger EG, Tekstra J, Prakken B, Brenkman AB, Carr IM, Markham AF, Bonthron DT, Wulffraat N
J Rheumatol 2015 Nov;42(11):2211-4. doi: 10.3899/jrheum.150364. PMID: 26523041
Nahar I, Al-Shemmeri M, Hussain M
Gulf J Oncolog 2007 Jan;1(1):71-6. PMID: 20084716

Recent clinical studies

Etiology

Hou Y, Lin Y, Qi X, Yuan L, Liao R, Pang Q, Cui L, Jiang Y, Wang O, Li M, Dong J, Xia W
Bone 2018 Jan;106:96-102. Epub 2017 Sep 28 doi: 10.1016/j.bone.2017.09.015. PMID: 28963081
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

Diagnosis

Hou Y, Lin Y, Qi X, Yuan L, Liao R, Pang Q, Cui L, Jiang Y, Wang O, Li M, Dong J, Xia W
Bone 2018 Jan;106:96-102. Epub 2017 Sep 28 doi: 10.1016/j.bone.2017.09.015. PMID: 28963081
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

Therapy

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

Clinical prediction guides

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

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