We report on two sisters, one 46,XX with normal female phenotype, the other 46,XY with ambiguous external genitalia and agonadism. Both have a low birth weight and microcephalic malformation syndrome leading to early death. The 46,XX patient also had a diaphragmatic defect. The XY sister, in addition to absence of gonads and Mùllerian and Wolffian derivatives, had severe hypoplasia of the pulmonary artery and its branches, multicystic kidneys, and pachygyria. This combination of malformations, in part, fits in the autosomal recessive condition described by Kennerknecht et al.  in a 46,XX and 46,XY pair of sibs with agonadism. The craniofacial appearance of our patients is similar to that observed in the 46,XY sister with agonadism reported by Kennerknecht et al. . On the other hand, intrauterine growth retardation, microcephaly, and pachygyria are not part of the phenotype of the Kennerknecht “syndrome” and agonadism was not present in our 46,XX patient. We suggest two hypotheses to explain the abnormal phenotype in our cases. The first is that they might represent the third sibship affected by the Kennerknecht syndrome with additional anomalies. Alternatively, our two sibs might have a Seckel or a Seckel-like syndrome. The 46,XY patient would then be the first case of Seckel syndrome with sex reversal and agonadism. © 2001 Wiley-Liss, Inc.