Werner's Syndrome: A Clinical-Roentgen Entity

IN 1904, Otto Werner (1) described a syndrome called“cataract in connection with scleroderma" which involved 2 brothers and 2 sisters in a family of 6 children. Thirty years later, Oppenheimer and Kugel (2) published the first complete report of Werner's syndrome in the American literature, as observed in twin brothers at Montefiore Hospital in New York City. Since then, 64 documented cases of this syndrome have been described (3-19), but for only 2 of these, were there authoritative autopsy observations. From the published literature Werner's syndrome may best be described as follows: The disease occurs with equal frequency in both males and females and becomes manifest shortly after adolescence. A variety of disturbances are noted at this time, including loss of the subcutaneous tissues and muscle mass of the extremities, progressive changes in the skin of the hands and feet, graying of the hair with premature alopecia, and impairment of normal growth. As the condition progresses, the extremities become increasingly thin, while the trunk becomes disproportionately stocky. Indolent ulcers frequently develop at pressure points in the lower extremities, usually in the region of the heels, toes, and malleoli of the ankles. The skin assumes a scleroderma-like appearance, with hyperkeratosis and atrophy. The hair over the eyebrows, pubis, axillae, and face is thinned and downy in appearance. Complete baldness supervenes at an early age, and the patient generally appears prematurely old. The voice becomes weak and high-pitched and examination may reveal a characteristic vascular web of the vocal cords. There is generalized premature arteriosclerosis, and zones of metastatic calcification are frequently observed in the skin and subcutaneous tissues. The skeleton shows varying degrees of osteoporosis, with osteoarthritis of the peripheral joints and spondylosis deformans. Juvenile cataracts are not unusual. Diabetes is often present. A majority of patients exhibit varying degrees of impotence and sterility. Siblings are frequently affected and forme jruste types have been described. The typical patient shows premature aging, shortness of stature, thin, spindly lower extremities, a large trunk, and facies characterized by beaking of the nose, shallow orbits, and loss of the periorbital connective tissue. The major pathological findings are related to the extensive arteriosclerotic changes in the coronary and peripheral vessels. The skin lesions, originally thought to be those of scleroderma, simply reflect hypoplastic and atrophic changes. The various endocrine organs which have been etiologically implicated at one time or another show no specific histologic abnormality. A striking finding is the frequent coexistence of neoplastic disease, which includes carcinoma of the breast, fibrosarcoma of the soft tissues, hepatoma, uterine sarcoma, and melanosarcoma of the skin. The etiology of this syndrome is unknown, although there are scattered reports indicating that endocrine dysfunction may be responsible. However, published data show no definitive findings to support this concept. We have had the opportunity of studying a total of 9 cases, 6 of which have come to autopsy. The purpose of this paper is to present our findings in this series. Clinical Material Eight cases have been collected from the files of the Montefiore Hospital in New York City since the early 1930's. Three of these—Cases 1, 2, and 3— have been previously reported (2, 3, 4). The ninth patient, hospitalized elsewhere, was a sibling of one of the Montefiore group (Case 6). Information supplied by this latter patient suggested the possibility of a similar condition in the sibling, and this was subsequently confirmed.