Unrecognized fracture both bones leg with hypertrophic callus in a child with hypohidrotic ectodermal dysplasia

Introduction

Ectodermal dysplasias (EDs) are a heterogeneous group of disorders characterized by a constellation of findings involving defects in two or more of the following: teeth, skin and its appendageal structures, including hair, nails, and eccrine and sebaceous glands. Hypohidrotic ectodermal dysplasia (HED) is manifested as a triad of defects: partial or complete absence of sweat glands, anomalous dentition, and hypotrichosis ¹ . In addition to these cardinal features, it may be associated with subtotal amelia, congenital renal agenesis and scoliosis ² , tibial aplasia ³ and brachydactyly ⁴ . We report here the first case of HED associated with unrecognized fractures of both bones of the lower leg and hypertrophic callus.

Case report

A 7‐year‐old boy was referred to us in May 2005. The patient had had symptoms of painful, rapidly increasing swelling and erythema of the left leg for the previous 5 weeks (Fig. 1). Clinical examination revealed diffuse bony, hard, tender, swelling of his left leg at the diaphysis of the tibia. The local temperature was not raised. He had a limited range of motion of the ankle with decreased ankle planter flexion and dorsiflexion due to pain. There were no signs of fluctuation and the regional lymph nodes were not enlarged. The child was well nourished and afebrile. There was no clear history of any preceding trauma, febrile episode or intravenous infusion in the limb. A general physical examination revealed dry, finely wrinkled skin over his entire body, and pegged teeth. The tips of his fingers were tapering and associated with onchondysplasia (1, 2). There was no neurological impairment. The erythrocyte sedimentation rate and total and differential white blood cell counts were within normal limits. Radiographs of the left lower leg showed fractures of both leg bones with hypertrophic callus in the proximal and middle third of the leg (Fig. 3). Bilateral radiographs of the hands showed resorption of the terminal phalanges (Fig. 4) and radiographs of the skull and mandible showed hypoplasia of the maxilla, hypodontia and conical teeth (Fig. 5). The serum calcium concentration was 9.1 mg/dL (range, 10.0–11.5 mg/dL), serum phosphorous was 5.4 mg/dL (range, 4.5–5.5 mg/dL), and serum alkaline phosphatase and electrolytes were within normal limits. Blood urea was 26 mg/dL (range, 20–35 mg/dL) and serum creatinine 0.8 mg/dL (range, 1–1.5 mg/dL). To confirm the diagnosis and rule out malignancy, a biopsy was performed. Biopsy of the swelling revealed features of callus (Fig. 6). A skin biopsy from the dorsum of the right hand revealed absence of sweat glands (Fig. 7). A plaster of Paris cast was applied to immobilize the limb for one month, after which he was started on a gentle range of exercises and continued physical therapy to maintain joint mobility. The pain and swelling gradually started to subside. However, unfortunately the child died during a febrile episode fifteen days after cast removal.

Figure 1.

Photograph of the patient showing swelling of his left leg and dry, finely wrinkled skin over his entire body. The tips of his fingers are tapering and associated with onchondysplasia.

Figure 2.

Photograph of the patient showing hypodontia and pegged teeth.

Figure 3.

Radiographs of the left lower leg show fracture of both bones with anterior bowing and hypertrophic callus.

Figure 4.

Radiographs of the both hands showing resorption of the terminal phalanges.

Figure 5.

Radiographs of (A) the skull and (B) mandible showing hypoplasia of the maxilla, hypodontia and conical incisors, with markedly dysplastic enamel.

Figure 6.

Photomicrograph of the biopsy from the leg lesion showing features of callus. Black arrow, woven bone; red arrow, cellular zone; white arrow, osteoid formation with fibro vascular background. (Hematoxylin and eosin staining, magnification ×100).

Figure 7.

Histopathology of the skin biopsy from the dorsum of the right hand shows slightly acanthotic epidermis with follicular plugging (white arrow). The underlying dermis shows a paucity of adenexal structures; while pilosebaceous apparatus is visible (black arrow), eccrine glands are absent. (Hematoxylin and eosin staining, magnification ×100).

Discussion

The EDs are a heterogeneous group of disorders characterized by developmental dystrophies of ectodermal structures. About 160 clinically and genetically distinct hereditary EDs have been described. Children affected by X‐linked recessive ED (Christ‐Siemens‐Touraine syndrome) are unable to sweat. The typical facies is characterized by frontal bossing; malar hypoplasia; a flattened nasal bridge; recessed columella; thick, everted lips; wrinkled hyperpigmented periorbital skin; and prominent, low set ears ¹ . The skin over the entire body is dry, finely wrinkled, and hypopigmented. A paucity of sebaceous glands may account for the dry skin. The hair is sparse, unruly, and lightly pigmented, and eyebrows and lashes are sparse or absent. Anodontia or hypodontia with widely spaced conical teeth is a consistent feature. Less commonly, stenotic lacrimal puncta, corneal opacity, cataracts, hypoplastic or absent mammary glands, and conductive hearing loss have been observed. The sweating deficit is a reflection of hypoplasia or absence of eccrine glands; this may be diagnosed by skin biopsy ¹ .

Congenital bone deficiency can occur in EDs, especially in association with ectrodactyly and clefting (the ectrodactyly–ectodermal dysplasia–cleft syndrome); that syndrome is inherited in an autosomal dominant fashion ⁵ . Other forms of skeletal involvement in HED include subtotal amelia, scoliosis, brachydactyly and tibial aplasia ² , ³ , ⁴ . Kaissi et al. reported severe skeletal anomalies of upper and lower limbs in the form of bilateral agenesis of the tibiae and fibulae associated with absence of the tarsal and metatarsal bones in the lower limbs; and total aplasia of the third finger, abnormal osseous bridging between the second and the fourth fingers and clinodactyly of the fifth finger in the upper limb ³ . Ellis and Creveld reported three cases of chondro‐ectodermal dysplasia with involvement of the long bones ⁶ . The long bones showed the short, thick bones that are characteristic of achondroplasia. In one of the reported cases the tibiae and fibulae were both short and heavy. The distal ossification centre of the fibula was unusually large on each side, and there was marked roughening and irregular condensation of bone at the distal ends of both tibiae and in the distal tibial centre of ossification. There was apparent fusion of the ends of the shafts of the fibulae with the distal ossification centres of both tibiae. The proximal ends of the tibiae were greatly widened and showed a small, irregular centre of ossification situated medially ⁶ . Nevertheless, to our knowledge an association between HED and spontaneous fracture and hypertrophic callus formation has never been reported. Hypertrophic callus formation needs to be differentiated from other conditions like myositis ossificans traumatica, sarcoma, calcinosis cutis, periostitis, and osteomyelitis. Lack of a good history of trauma may prompt the clinician to be more aggressive in identifying the process by taking a biopsy. We performed biopsy of the swelling to diagnose the pathology as there was no preceding traumatic/ febrile/ intravenous infusion episode and moreover, the fractures were unrecognized.

The gene for anhidrotic ectodermal dysplasia (EDA) has been cloned and encodes ectodysplasin A (EDA‐A) ⁷. It was reported recently that the EDA‐A gene is expressed by osteoblasts in developing embryos ⁸ . Hill et al. reported that mutation of gene EDA‐A results in bony changes in the tail vertebrae of the Tabby mouse, but not much change in the tibiae ⁹ . It is unclear from the literature whether the quality of the bone is also affected in human beings, nor whether or not this animal model is applicable to human beings. In the present case, the spontaneous fractures may have been stress fractures and have led to periosteal bone‐forming cell stimulation and subsequent formation of hypertrophic callus due to non‐immobilization. The ultimate outcome of the fractures and hypertrophic callus was cut short by the sudden demise of the patient. Although this new association could be a chance occurrence, its description may alert physicians to look for similar combinations and report these, as such reporting may lead to better syndrome delineation and patient care and reduction of functional impairment.

Disclosure

This manuscript does not contain information about medical device(s)/drug(s). No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.