|Year : 2020 | Volume
| Issue : 4 | Page : 604-606
Progressive osseous heteroplasia: A rare case report
Kananbala Sahu, Arpita N Rout, Liza Mohapatra, Prasenjeet Mohanty
Department of Skin and V.D., S.C.B.M.C.H., Cuttack, Odisha, India
|Date of Web Publication||13-Jul-2020|
Arpita N Rout
Department of Skin and V.D., S.C.B.M.C.H., Cuttack - 753 001, Odisha
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Progressive osseous heteroplasia (POH) is a rare genetic condition of progressive extraskeletal bone formation. POH is clinically suspected by cutaneous ossification, usually presenting in early life, that involves subcutaneous and then subsequently deep connective tissues, including muscle and fascia. We report a case of POH in a 3-year-old child with multiple nontender subcutaneous nodules which, on radiology and histopathology, showed intracutaneous bone formation. Although there is no specific and effective treatment, knowledge about this entity is necessary for early detection and genetic counseling of parents.
Keywords: Extraskeletal bone formation, intramembranous ossification, osteoma cutis
|How to cite this article:|
Sahu K, Rout AN, Mohapatra L, Mohanty P. Progressive osseous heteroplasia: A rare case report. Indian Dermatol Online J 2020;11:604-6
|How to cite this URL:|
Sahu K, Rout AN, Mohapatra L, Mohanty P. Progressive osseous heteroplasia: A rare case report. Indian Dermatol Online J [serial online] 2020 [cited 2020 Aug 4];11:604-6. Available from: http://www.idoj.in/text.asp?2020/11/4/604/289631
| Introduction|| |
Progressive osseous heteroplasia (POH) is a rare genetic condition of progressive extraskeletal bone formation. The presenting features of this condition include early-onset cutaneous ossification, sometimes involving subcutaneous and even deep connective tissues like muscles and fascia. Because of its rarity, most of the physicians are unaware of the condition. Here, we report a case of a 3-year-old child who presented with bone formation on cutaneous and subcutaneous planes. The diagnosis of progressive osseous heteroplasia was proven by plain radiography and histopathology. We report this case because of its rarity and to create awareness among physicians.
| Case Report|| |
A 3-year-old male child, born out of nonconsanguinous marriage, presented with three slow-growing painless hard masses over the outer aspect of right leg since the age of 2 months. The child had been delivered at full term without any congenital malformation. He developed multiple asymptomatic solid elevated skin-colored lesions which in course of time coalesced to form large hard masses. There was history of low birth weight and delay in gross-motor type of developmental milestones, but there was no mental retardation or gait abnormality. There was no history of trauma, prior inflammation, or similar lesions in the family members. On examination, there was a single large non-tender subcutaneous hard mass of size 4 cm × 5 cm over anterolateral aspect of right thigh without any surface change [Figure 1]. Skin could be pinched over the lesion. There were two similar smaller lesions of size 2 cm × 3 cm and 2 cm × 2 cm with surface showing atrophy and scaling over the outer aspect of right lower leg [Figure 2]. There was no other skeletal deformity. Plain radiograph of lower limbs in anteroposterior and lateral views showed calcified areas in subcutaneous plane corresponding to the areas of the skin lesions [Figure 3]. The serum levels of calcium, parathyroid hormone, creatinine phosphokinase, alkaline phosphatase, and lactate dehydrogenase were normal. Serum phosphate level was slightly raised (5.5 mg/dL). Histopathological examination showed irregular woven bone spicules in the deep dermis [Figure 4] and [Figure 5]. Genetic study was not available in our setup. On the basis of clinical, histopathological, and radiographic features, a final diagnosis of progressive osseous heteroplasia was made. The parents were counseled about the prognosis of the condition, and that no active intervention was helpful. The patient was referred to the physiotherapy department.
|Figure 1: Skin colored to slightly erythematous hard plaques and nodules on the anterolateral aspect of right thigh and lateral aspect of right lower leg. Biopsy scars are visible|
Click here to view
|Figure 3: (a): X-ray of right lower limb (lateral view) showing reticular pattern of ectopic bone formation in dermis and subcutis. (b): X-ray both lower limbs (anteroposterior view) showing ectopic bone formation in dermis and subcutis in lateral part of right thigh|
Click here to view
|Figure 4: (a): Scanner view showing unremarkable epidermis with intramembraneous ossification and bony spicules in dermis (H and E ×40). (b): Low power view showing intramembraneous ossification and bony spicules in dermis (H and E ×100)|
Click here to view
|Figure 5: Highpower view showing osteoblasts with eccentrically placed nuclei embedded in eosinophilic matrix (H and E ×400)|
Click here to view
| Discussion|| |
Disorders of extraskeletal bone formation are classified as nonhereditary and hereditary conditions. Nonhereditary forms usually present at a later age or with prior history of trauma, surgery or arthropathy. Hereditary forms include fibrodysplasia ossificans progressiva, Albright hereditary osteodystrophy, pseudohypoparathyroidism, plate-like osteoma cutis, and progressive osseous heteroplasia.,
Clinically progressive osseous heteroplasia appears as hard maculopapular lesions which over time coalesce to form plaques and spread into deeper connective tissues including fascia, skeletal muscle, tendon, and ligament. Small spicules of dermal bone may occasionally extrude through the epidermis although bone formation does not originate in the epidermis. Extensive ossification of the deep connective tissues can result in ankylosis of affected joints and growth retardation of involved limbs. Hormonal abnormalities are rarely associated with POH, but parathyroid hormone resistance is never seen. POH is caused by heterozygous inactivating mutations of GNAS, the gene encoding the alpha subunit of the G-stimulatory protein of adenylyl cyclase.
These patients have an average age of onset earlier than 1 year and usually have low birth weight. There is also a striking lateralization of lesions in a dermato-myotomal distribution.
Radiographic appearance of POH shows a distinctive reticular pattern of web-like ectopic bone involving soft connective tissues from the dermis down to skeletal muscle. Lesional biopsy shows mostly intramembraneous ossification, with 20% showing endochondral ossification and 30% both types.
POH is diagnosed on the basis of three major criteria: superficial heterotopic ossification that progresses to deep connective tissue; two or fewer Albright hereditary osteodystrophy features, excluding heterotopic ossification; and no parathyroid hormone resistance [Table 1]. In addition to these key diagnostic criteria, there are several clinical findings that support the diagnosis of progressive osseous heteroplasia [Table 1].
Fibrodysplasia ossificans progressiva differs from progressive osseous heteroplasia in having characteristic malformed monophalangic valgoid short big toes, short thumbs, fifth finger clinodactyly, malformed cervical vertebrae, short broad femoral necks, deafness, scalp baldness, mental retardation, and physical handicap due to progressive ectopic ossification. Similarly, Albright hereditary osteodystrophy is typically associated with dysmorphic “moon” facies, obesity, short stature, brachydactyly, and end-organ resistance to parathyroid hormone. Pseudohypoparathyroidism differs from progressive osseous heteroplasia in having abnormal endocrine function, and associated Albright hereditary osteodystrophy features. In osteoma cutis, true bone is formed in the skin.
Surgical removal does not cure the condition as there is recurrence in most patients. Physiotherapy helps by preserving movement and prevention of skin breakdown. The parents need to be counseled to continue education as the child is mentally normal and disease does not seem to progress rapidly in adults.
Our patient was having features of both superficial and deep heterotopic ossification, with normal serum levels of parathyroid hormone and calcium. There were also other supporting clinical findings of onset younger than one year, leanness, lateralization in a dermo-myotomal pattern, radiological evidence of reticular pattern of bone formation, and histopathological evidence of intramembranous ossification. We report this case because of its rarity, and to create awareness among the dermatologist and pediatricians regarding the benign nature of this condition, which may be confused with other serious hereditary forms of extraskeletal bone formation. As this condition might create apprehension among family members, early diagnosis and proper counseling play a vital role in restoring the child's normal physical and mental health.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to b'e reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kaplan FS, Craver R, MacEwen GD, Gannon FH, Finkel G, Hahn G, et al
. Progressive osseous heteroplasia: A distinct developmental disorder of heterotopic ossification. Two new case reports and follow-up of three previously reported cases. J Bone Joint Surg Am 1994;76:425-36.
Singh GK, Verma V. Progressive osseous heteroplasia in a 10-year-old male child. Indian J Orthop 2011;45:280-2.
] [Full text]
Bastepe M, Jüppner H. GNAS locus and pseudohypoparathyroidism. Horm Res 2005;63:65-74.
Weinstein LS, Liu J, Sakamoto A, Xie T, Chen M. Minireview: GNAS: Normal and abnormal functions. Endocrinology 2004;145:5459-64.
Shore EM, Ahn J, Jan de Beur S, Li M, Xu M, Gardner RJ, et al
. Paternally inherited inactivating mutations of the GNAS1 gene in progressive osseous heteroplasia. N
Engl J Med 2002;346:99-106.
Liu JJ, Russell E, Zhang D, Kaplan FS, Pignolo RJ, Shore EM. Paternally inherited gsα mutation impairs adipogenesis and potentiates a lean phenotype in vivo
. Stem Cells 2012;30:1477-85.
Cairns DM, Pignolo RJ, Uchimura T, Brennan TA, Lindborg CM, Xu M, et al
. Somitic disruption of GNAS in chick embryos mimics progressive osseous heteroplasia. J Clin Invest 2013;123:3624-33.
Adegbite NS, Xu M, Kaplan FS, Shore EM, Pignolo RJ. Diagnostic and mutational spectrum of progressive osseous heteroplasia (POH) and other forms of GNAS-based heterotopic ossification. Am J Med Genet A 2008;146:1788-96.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]