Necropsy findings in a child with FG syndrome.

at 25 years of age she had received no hormonal therapy and had experienced no menstrual bleeding. At 6 years of age she had 'Bright's disease' which resolved after several months' stay in hospital. Her general health thereafter was excellent apart from intermittent, mild peripheral oedema. Her physical examination showed a height of 155 cm, a weight of 62 kg, a blood pressure of 130/70, moderate obesity, and a grade 2/4 systolic ejection murmur. She had normal sexual development. The pelvic examination was normal apart from failure to palpate either ovary. Laboratory studies included FSH of 183 IU/l (normal 2-5 to 27), LH of 256 IU/l (normal 3 to 250), T3 uptake of 30%, and T4 of 88 ,ug/dl. Analysis of peripheral lymphocytes by standard Q, G, and C banding showed a 47,XX,i(Xq) karyotype in all cells. Fibroblasts cultured from a forearm skin biopsy also showed only 47,XX,i(Xq). Late labelling studies with BrdU in lymphocytes and fibroblasts showed two late replicating X chromosomes in all cells analysed, one of which was the i(Xq) chromosome. Two abnormal events must have given rise to the 47,XX,i(Xq) karyotype: non-disjunction resulting in the aneuploidy (47 chromosomes) and the formation of the isochromosome X. There is no simple explanation to relate the two abnormalities to a single event, or to explain one abnormality as predisposing to the other. Assuming that the 47,XX,i(Xq) karyotype in our patient was related to the premature ovarian failure, this would be difficult to reconcile with the report of King and Schimke.' Other explanations can be offered for this apparent discrepancy. First, the 47,XX,i(Xq) state is not associated with abnormal gonadal function and our patient's gonadal failure is secondary to a cause unrelated to her karyotype. Secondly, the 47,XX,i(Xq) in our patient is the cause of her gonadal failure and the normal phenotype in the patient of King and Schimke occurred as the result of an undetected mosaicism for a normal cell line. Thirdly, the patient of King and Schimke represents the normal phenotypic expression of the 47,XX,i(Xq) karyotype and our patient's gonadal failure was the result of an undetected mosaicism. Either 45,X or 46,X,i(Xq) might be expected to have occurred and either would be an adequate explanation for the premature ovarian failure. Reconciliation of the difference between these two cases will require additional reports of patients with the 47,XX,i(Xq) karyotype. It will be important that an extensive search for mosaicism is conducted in such cases. Necropsy findings in a child with FG syndrome