Low birth-weight, microcephalic malformation syndrome in a 46,XX girl and her 46,XY sister with agonadism: Third report of the Kennerknecht syndrome or autosomal recessive Seckel-like syndrome with previously undescribed genital anomalies

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 bir th weight and microcephalic malformation syndrome leading to early death. T he 46,XX patient also had a diaphragmatic defect. The XY sister, in additio n to absence of gonads and Mullerian and Wolffian derivatives, had severe h ypoplasia of the pulmonary artery and its branches, multicystic kidneys, an d pachygyria. This combination of malformations, in part, fits in the autos omal recessive condition described by Kennerknecht et al. [1993] 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 rep orted by Kennerknecht et al. [1995]. On the other hand,, intrauterine growt h retardation, microcephaly, and pachygyria are not part of the phenotype o f the Kennerknecht "syndrome" and agonadism was not present in our 46,XX pa tient. We suggest two hypotheses to explain the abnormal phenotype in our c ases. 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 woul d then be the first case of Seckel syndrome with sex reversal and agonadism . (C) 2001 Wiley-Liss, Inc.