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Editor—True agonadism, characterised by the absence of gonads in both XY and XX patients, is a rare, mostly sporadic, and isolated condition. Its association with diaphragmatic hernia seems to be extremely rare and has always been described associated with multiple congenital malformation (MCA) syndromes of unknown origin. Sex reversal and diaphragmatic hernia have been described once with a heterozygous WT1mutation in a sporadic case.1 The association of normal feminisation, absent gonads, and diaphragmatic hernia in two XY sibs without any other malformation suggested other diagnostic possibilities. Since further investigations did not find any chromosomal or known genetic cause for this familial sex reversal syndrome, we suggest that these cases could represent a new sex reversal syndrome, which could be either autosomal recessive or X linked, and may result from either unreported mutations ofWT1 or anomalies of other developmental genes.
The proband (fig 1, II.4) is the fourth child of non-consanguineous, healthy parents with an unremarkable family history. Their first child (II.1), a girl born at term in 1989, died of severe respiratory distress at 2 days of age after surgery for a left diaphragmatic hernia. She was of normal size (weight 3200 g, 50th centile) and according to the paediatricians not dysmorphic. No additional malformation was found at necropsy apart from the large left diaphragmatic hernia and a single umbilical artery. Chromosomal analysis was not performed. Two subsequent pregnancies resulted in normal, healthy, male children (II.2, II.3).
At 34 weeks' gestation of the fourth pregnancy, ultrasonography detected dextrocardia owing to a left diaphragmatic hernia involving the stomach, left lobe of the liver, and numerous intestinal loops. Chromosomal analyses were performed on both lymphocytes from fetal blood and fibroblasts from amniotic fluid. They were normal male: 46,XY. Delivery was spontaneous at 37 weeks' gestation. …