This paper by Erik Niebuhr reviews 12 cases of Down's syndrome associated with a G/G tandem translocation between the long arms of chromosome 21. The author suggests that trisomy of a specific segment on chromosome 21 (21q22) might be the pathogenetic factor in Down's syndrome. Key observations include: 1. Patients with G/G tandem translocations exhibit varying clinical features and mental development, with some showing more typical features and others less so. 2. Fluorescence studies and staining techniques indicate that the translocation chromosome is formed by breaks distally on both chromosomes, leading to minimal loss of chromosomal material. 3. The presence of satellites on both ends of the translocation chromosome suggests distal breaks and subsequent loss of material at the long arm of chromosome 21. 4. The clinical features are less typical in cases with smaller translocation chromosomes, and patients with Down's syndrome due to Robertsonian translocations and free trisomy show identical phenotypes. These observations support the hypothesis that trisomy of the distal segment (21q22) is essential for the development of typical features in Down's syndrome. Further research using new staining techniques is proposed to validate this hypothesis.This paper by Erik Niebuhr reviews 12 cases of Down's syndrome associated with a G/G tandem translocation between the long arms of chromosome 21. The author suggests that trisomy of a specific segment on chromosome 21 (21q22) might be the pathogenetic factor in Down's syndrome. Key observations include: 1. Patients with G/G tandem translocations exhibit varying clinical features and mental development, with some showing more typical features and others less so. 2. Fluorescence studies and staining techniques indicate that the translocation chromosome is formed by breaks distally on both chromosomes, leading to minimal loss of chromosomal material. 3. The presence of satellites on both ends of the translocation chromosome suggests distal breaks and subsequent loss of material at the long arm of chromosome 21. 4. The clinical features are less typical in cases with smaller translocation chromosomes, and patients with Down's syndrome due to Robertsonian translocations and free trisomy show identical phenotypes. These observations support the hypothesis that trisomy of the distal segment (21q22) is essential for the development of typical features in Down's syndrome. Further research using new staining techniques is proposed to validate this hypothesis.