Recurrent non-immune hydrops fetalis with gracile bones and dysmorphic features in siblings

We report on two siblings with recurrent non-immune hydrops fetalis of unknown etiology. The proposita was born at 32-week gestation with hydrops fetalis. She died at less than 1 hr of age despite resuscitative efforts. Her brother was born 1 1/2 years later to the same parents. He was also born at 32-week gestation and lived 40 min. At birth, both individuals were noted to have marked edema of the entire body, slightly low set ears, small nose, mild micrognathia, small chest, camptodactyly, single transverse palmar creases, rhizomelic shortening of the upper extremities, slight ankle varus deformity bilaterally and bilateral humeral fractures. Postnatal chromosomal analysis of the first patient was normal. In both cases, evaluation for lysosomal storage disorders utilizing skin fibroblasts was negative. The radiographs and autopsies were done on both patients and showed diffuse soft-tissue edema, gracile bones, especially in the upper extremities and ribs, and bilateral humeral fractures in both children. Both patients had absence of germ cells. The skeletal system in both appeared otherwise normal. After testing for infectious, chromosomal, hematological, hepatic and metabolic causes, we were unable to identify the etiology of the condition in the above patients. Further, we have been unable to identify a reported genetic condition with the features present in these cases. As such, we believe that the disorder in the individuals reported here represent a new autosomal recessive condition.