Hirsutism, Skeletal Dysplasia, And Mental Retardation

Clinical Features

Wiedemann et al. (1993) described a well-studied patient followed from infancy to age 19 years. He was born to a 34-year-old mother and an unrelated 37-year-old father. Features of the syndrome from which the patient suffered included extraordinary hirsutism, marked brachycephaly, abnormal position of thumbs, pes cavus with claw toes, an abnormal face, and mental retardation. The facial features consisted of slightly antimongoloid slant of the right palpebral fissure, epicanthic folds, broad nasal root, perhaps mild hypertelorism, and somewhat everted prominent lower lip. At the age of 16, the patient developed pain, swelling, and redness of several finger joints, and he was found to have elevated serum uric acid. This elevation and the symptoms of gout responded promptly to allopurinol. Skeletal anomalies became evident after the end of his first year. The neck became very long, and the thorax became much longer and narrower over the course of the years, with a prominent manubrium. The shoulders were down-sloping and the elbow joints unusually prominent. The right hallux was abnormally placed with chronic subluxation. There was coxa valga bilaterally with subluxation of both hip joints. Height was in the normal range. Oster et al. (1994) reported data collected on the patient reported by Wiedemann et al. (1993) at age 20 after 10 days without medication. The data were interpreted as indicating that the hyperuricemia was not caused by overproduction or by a defect in either APRT (102600) or HPRT (308000). Also, overproduction of uric acid caused by phosphoribosylpyrophosphate synthetase superactivity (300661) was excluded. Oster et al. (1994) concluded that hyperuricemia was probably due to reduced renal excretion of uric acid since renal clearance of uric acid and fractional uric acid clearance were below the normal range for age and sex.