• Two brothers, aged 15½ and 13½ years, with dwarfism, microcephaly, and advanced sexual and skeletal maturation are described. One patient was mentally retarded. The parents were first cousins. Endocrine studies of these patients documented low growth-hormone levels after clonidine and insulin stimulation and blunted growth-hormone response to growth hormone releasing hormone. Gonadotropin releasing hormone stimulation produced no changes in levels of luteinizing and follicle-stimulating hormones. Basal levels of 17-α-hydroxyprogesterone were elevated in the two patients and increased further in response to stimulation with corticotropin. Levels of testosterone, dehydroepiandrosterone sulfate, and androstenedione were variably increased in both patients and showed a proportional increase on stimulation with human chorionic gonadotropin. To our knowledge, this is the first report of a familial association between growth-hormone deficiency and advanced bone and sexual maturation. A pituitary and an independent adrenal defect could account for the observations in these patients, but in view of the familial recurrence, a common underlying defect is possible.
(AJDC. 1993;147:170-173)