A report of two cases of Werner's syndrome and review of the literature

Journal of Orthopaedic Surgery, Dec 2003 by Yamamoto, K, Imakiire, A, Miyagawa, N, Kasahara, T

ABSTRACT

Two cases of Werner's syndrome are reported. The first case is that of a man with grey hair since his 20s, and alopecia since aged about 50 years. At the age of 53 years, Werner's syndrome was diagnosed, along with a malignant soft tissue tumour of the hand. The patient underwent ray amputation for the tumour. The subsequent histopathological diagnosis was synovial cell sarcoma, and the patient died of lung metastasis at 15 weeks postsurgery. The second case is that of a woman diagnosed with diabetes mellitus when aged 34 years. At 39 years, a bilateral cataract was diagnosed and at 40 years, diabetic gangrene of the left calcaneal region and calcaneal osteomyelitis necessitated left below-knee amputation. The incidence of Werner's syndrome in Japan is extremely high (about 1000 of the around 1300 cases reported worldwide) compared to other countries. Most patients develop malignant tumour or arteriosclerosis, the most important complications of this syndrome. The average life expectancy for patients with Werner's syndrome is 46 years. The incidence of epithelial cancer and mesenchymal sarcoma is 10 times that of the general population. The onset of symptoms of Werner's syndrome generally precedes any later symptoms of associated conditions, such as malignant tumour. Therefore, early recognition of Werner's syndrome is important to assist identification of malignant tumours at an early stage in this patient group.

Key words: arteriosclerosis; chondrosarcoma, mesenchymal; ossification, heterotopic; osteomyelitis; sarcoma, synovial; Werner syndrome

INTRODUCTION

Werner's syndrome is a hereditary systemic disease. Clinical characteristics including small stature, scleroderma-like skin alterations, juvenile cataracts, and premature facial ageing. This syndrome has been reported most frequently in the ophthalmologic and dermatologie literature, but has also been reported in the orthopaedic literature due to its complications of ectopic calcification, refractory ulcer, and joint contracture. We report 2 cases of Werner's syndromeone associated with a malignant soft tissue tumour of the hand, and the other associated with a refractory calcaneal ulcer.

CASE REPORTS

Case1

A male patient presented to the Department of Surgery, Tokyo Medical University when aged 54 years. His major complaints at this time were swelling, and pain in the left hand. The medical history taken identified that his parents were consanguineous, but that there were no symptoms of note in his 5 siblings and 2 children. The patient reported that he had been short in stature since childhood, and grey-haired since his 20s. he had noticed his voice weakening with a high pitch since about the age of 30 years, along with skin atrophy in the peripheries of the extremities. At the age of 37 years, the patient had an ulcer over his right ankle joint, which took 6 months to heal. When aged 40 years, he had surgery for a left eye cataract. When aged about 50 years he noted increasing alopecia. he also commenced treatment for angina at this time. At the age of 53 years, he visited a doctor in response to dull pain and a small growth in the left hypothenar region. Two months later, he was referred to our department due to abnormal findings of the 4th and 5th metacarpi on X-ray.

General physical examination on admission revealed that he was only 142.5 cm in height and 41.5 kg in weight. His extremities were thin. Atrophied skin, and decreased subcutaneous fat and muscle were observed in the periphery of the extremities. His external genitalia appeared atrophied. There was extensive abnormal pigmentation of the skin and telangiectasis evident. His hair was generally scarce and markedly grey. His face looked aged, and he had a beak-shaped nose. His voice was high-pitched and hoarse. Range of motion of the ankle joints was limited to -5" on dorsiflexion and 30" on plantar flexion, and mobility of the skin was markedly reduced. The ulnar surface of the left hand was oedematous. A partially irregular, elastic, hard mass was felt on the surface between the 4th and 5th metacarpi, showing adhesion to the skin. Heat and tenderness were noted on examination but no fluctuation or pulsation was evident.

Laboratory findings included decreased glucose tolerance, decreased natural killer cell activity, and an increased T4/8 ratio. X-ray findings at presentation included irregular erosion of the cortex of the 4th and 5th metacarpi and the distal phalanx, and a tumour shadow in the soft tissue on the ulnar surface (Fig. 1). Angiography of the hand revealed arterial deviation, contraction, and calibre variation, but no tumour stain, blood pool, or arteriovenous shunt. Computed tomography (CT) scanning of the hand indicated a broad defect of the palmar cortex of the 4th and 5th metacarpi, and a soft tissue tumour shadow with an indistinct border.

In addition, calcification was identified in the quadriceps tendon and patellar ligament (Fig. 2), as well as in the triceps tendon and the Achilles tendon. Based on the above findings, a diagnosis of Werner's syndrome associated with malignant soft tissue tumour in the hand was made.