Segregation of a t(1;3) translocation in multiple affected family members with both types of adjacent-1 segregants.

A subtle balanced translocation involving the terminal regions of 1q and 3p was identified in a large family by high-resolution karyotype analysis and confirmed by fluorescence in situ hybridization (FISH) analysis. In this family, segregation of a balanced t(1:3)(q42.3;p25) chromosome translocation led to two types of viable unbalanced complements. The proband inherited the derivative chromosome 3, resulting in partial trisomy of 1q and partial monosomy of 3p. A paternal uncle and cousin had the reciprocal rearrangement with a derivative of chromosome 1, resulting in partial monosomy for 1q and partial trisomy for 3p. While profound mental and physical retardation and congenital heart defects were characteristics for both rearrangements, facial dysmorphism was quite distinct for each imbalance. Individuals who had the derivative chromosome 3 had a long face, wide eyebrows, small palpebral fissures, hypertelorism, prominent glabella, a large tip of the nose, long philtrum with thin upper lip, and low set-ears. In contrast, family members with the derivative of chromosome 1 had a tall forehead with bifrontal narrowing, full and large cheeks, and large simple ears. Since the translocated segments are small and approximately equal in size in this family, it is not surprising that viability was seen in individuals with both types of adjacent-1 segregation. In this kindred, the ratio of normal to abnormal individuals born to balanced carriers is believed to be about 1:1.5. This suggests that the recurrence risk for carriers is 50%. Copyright 2003 Wiley-Liss, Inc.