Progressive Diaphyseal Dysplasia

ANUNUSUAL SYNDROME characterized by progressive skeletal changes, wasting, and anomalous neuromuscular signs as observed in four children over a seven-year period is being presented. A preliminary report on the first two of these patients was published by Riley and Shwachman in 1943. Additional information has since been gained on the course of this disease. Descriptions of similar disorders have not been found in the available literature.

CASE 1: M. M. (Fig. 1, A and B) was first seen in June 1941 at the age of four years and three months, because of a waddling gait, easy fatigability, and failure to gain weight. The family, birth, and neonatal histories were non-contributory. The child's development was normal, except for some difficulty in walking, up to two and one half years, at which time she had pertussis, followed by loss of appetite and persistent inability to gain weight normally. She was hospitalized at the age of four years and ten months for study.

The significant findings were: underweight, a gait of straight-legged, wide-based, waddling type, hyperactive deep tendon reflexes and inconstant ankle clonus. Studies of the genito-urinary, gastrointestinal, and circulatory systems revealed no abnormalities. Roentgen examination at this time siowed changes in the diaphyses of the long bones as illustrated in Figures 2 (B), :3, and 4. The laboratory examinations, including blood Hinton test, tuberculin test 1–1000, complete blood count, spinal fluid study, and complete urine study, were within normal limits. The serum protein, calcium, phosphorus, alkaline phosphatase, and non-protein nitrogen were normal. A biopsy from the tibia at this time revealed increased density of cortical bone with evidence of active resorption (Fig. 5).

The patient was followed at frequent intervals, and the striking feature at each visit was her failure to gain weight, attributed partly to extreme anorexia. During a short period of intensive dietary therapy in the hospital she gained well, but this gain was not sustained. Although she remained consistently far below normal weight, her height was in the low normal range. Table I shows the weight and the height at different ages, with the percentile distribution.

The child always tired easily and was never able to run. Dr. Bronson Crothers was instrumental in placing her under appropriate institutional care, where she is now happily adjusted and competitive activities are minimized. A biopsy from the ulna obtained in April 1947 is shown in Figure 6. Extreme and actively increasing disturbance of the bony architecture was noted, without evidence of inflammation. Roentgenograms at frequent intervals illustrate the progressive nature of the long bone involvement (Fig. 3). The blood non-protein nitrogen, serum protein, glucose tolerance, cholesterol, calcium, phosphorus and alkaline phosphatase examinations have remained normal during the seven-year observation period.