The concurrence of Saethre-Chotzen syndrome and malignancy in a family with in vitro immune dysfunction.

The occurrence among 13 siblings of a malformation-mental retardation syndrome and diverse malignancies was investigated for etiologic relationship by clinical, genetic, immunologic, and virologic techniques. Three sisters and their father had Saethre-Chotzen syndrome, an autosomal dominant trait with craniosynostosis and asymmetric facies. One affected sister also had nasopharyngeal carcinoma; tow nondysmorphic brothers had Hodgkin's disease, and another had seminoma with teratocarcinoma of the testis. Decreased in vitro lymphocytic proliferation to various mitogens was observed in both available siblings with tumor, one sibling with Saethre-Chotzen syndrome, and two clinically normal siblings and their father. Both parents and all siblings had normal karyotypes and no increase of antibodies to Epstein-Barr virus. The malformation syndrome and the various neoplasias segregated independently of each other and of 47 genetic markers, including histocompatibility antigens (HLA). This study illustrates an approach to defining etiology when rare disorders cluster in a family and suggests that the occurrence of malignancies in this family may be related to subclinical immune dysfunction. Whether the Saethre-Chotzen syndrome predisposed to malignancy, perhaps through impaired immunity, awaits additional observations.